Yale Psychiatry Grand Rounds: Lisa Feldman Barrett

October 14, 2019

The Power of Predictions: An Emerging Paradigm for Studying Brain, Body, and Mind

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00:01Alright Good morning. Everyone let's make a start. It is a huge honor and a pleasure for me to introduce Lisa Feldman Barrett. Lisa is a University distinguished professor of Psychology Northeastern University.
00:14With appointments at Harvard Medical School and Mass General Hospital in psychiatry and radiology. She's a 2019 Guggenheim Fellow. She has a NH directores Pioneer Award for her groundbreaking work on emotion in the brain.
00:30She's an elected Member of the American Academy of Arts and Sciences and the Royal Society of Canada. She's president of the Association for psychological science, where somehow she also finds time to write blogs, most recently on the publication arms race an topically with Halloween around the corner on zombie ideas. These ideas that have been so thoroughly refuted empirically. And yet they refuse to die like the idea that vaccines cause autism and I'm sure some of you think predictive coding 2.
01:00So she's authored over 200 peer reviewed publications in various high profile journals nature neuroscience nature reviews neuroscience in motion psychological science ticks and 10s. But for me. It's her most recent book how emotions are made The Secret Life of the brain that I'm most excited about. I think I've gifted it to my friends and family more than any other book, particularly ones you don't really understand what it is that I do. They now do having read her book? Which I'm a little bit jealous about?
01:30It's a really incisive and broad, ranging synthesis of emotion in the brain.
01:36Through the lens of predicted processing, which is a really powerful account and through its lens. I think she's been able to Unite sort of apparently desperate accounts of how emotions come about from people like William James and Walter Cannon. I always like to ask people I introduced for a fun fact about themselves and least it tells me that she's unable to walk and talk about exciting ideas at the same time, so this morning. I think she's probably going to be rooted to the spot and delighted to host her an really looking forward to her tool. Thank you for coming.
02:14Good morning, everybody. Thank you to fill for the invitation and also for the very, very lovely introduction, so today. I'm not going to be talking to you about emotion per say. Although I'm happy to use some evidence about the study of emotion to make the point that I want to make today. I want to talk to you more broadly about predicted processing as a paradigm for understanding.
02:45How a brain in a body surrounded by other brains and bodies creates a human mind and what might go wrong with the mental features of life that we experience in life based on how brains and bodies work.
03:03Anne for audiences like this in my experience. It's usually good to try to pitch. The talk kind of out of general level instead of dictating a deep dive into the computational details of the data so that's what I'm going to do today. But if you have specific questions about the details. Feel free to ask because I have a bunch of data slides that I'll be talking that I can talk around as well, but but mostly what I want to do today is just give you a feel for.
03:34The potency and also the big questions of this framework and so to start a sof I'm going to.
03:44Cover the history of psychological science in one slide.
03:52So I think this is relevant for psychiatry audience because we study the mind and as psychologists and psychiatrists and also his neurologists and so on.
04:04And all of us pretty much since the time of play dough have been using a set of what philosophers call folk. Psychology categories or common sense categories. These are these make up the typology of mental faculties that organize how we understand what a mind is to think, to feel to perceive and since the 19th century.
04:35When psychology became a science by taking mental philosophy. The categories of mental philosophy, thinking feeling perceiving and so on, and attempting to find the brain basis of those mental categories, using the scientific tools available at the time, which was 19th century, Physiology, and neurology.
04:58And so basically since the birth of psychology neurologist physiologists and then later psychologists began to search for the physical basis of these categories using a paradigm from 19th century, Physiology, which is where you apply a stimulus and then you observe a response.
05:16And for decades in psychology, and elsewhere. Scientists were unable to find the physical basis of these mental categories for emotion, and cognition and so on.
05:25And so they decided to take another experimental approach.
05:32And that is the approach of functionalism where science of understanding what a mind is and how a mind works and from there, it was a very quick jump.
05:43To behaviorism and infamous phase of psychology, where the mine disappeared as a topic of inquiry at all.
05:55Now behaviorism was not a total loss, even though it was a very infamous period in psychology. It launched decades of careful research on brain circuitry. Some of which we still use today. But scientists after a couple of decades became profoundly dissatisfied with behaviorism because.
06:17It ignores the basic fact that every single person in this room knows.
06:22And that is that you have a mind.
06:27And in every waking moment of your life your mind is moving from one mental state to another.
06:35And mental states have to be explained in scientific terms. If we're ever going to be able to treat and even prevent mental illness. So, in the 1960s, the cognitive revolution in psychology reinstated the topic of the mind for scientific inquiry.
06:53And this revolution gave birth to cognitive neuroscience and all of the neuroscience is that UM sort of evolved out of that affect of neuroscience and social neuroscience and pick a topic and there's a neuroscience for it.
07:09Using brain imaging, which as you know peers into the brains of awake experiencing humans and attempts to measure neural activity.
07:17But it was faculty psychology, all over again basically for decades, human neuroscience was organized around. These mental faculties. That's why we have a cognitive neuroscience and a social neuroscience and affective neuroscience people speak about the emotional brain and they speak about the cognitive brain and the attention brain and the social brain, but you don't have forebrains you have one brain.
07:43And this has been I think a bit of an epiphany at least in the brain imaging world because the shiny new toys that we developed with brain imaging. It's not that they failed to teach us something at all. It's that they taught taught us something we didn't expect and that is that we don't have different parts of the brain that are dedicated to thinking and feeling your brain is not a battleground between cognition and emotion.
08:13You know in the struggle for your behavior that's a narative that we've had since Plato. It's a cherished narrative that appears in law and it appears in economics, but it actually is not respected by the brain by the anatomy of the brain are by the functioning of the brain and so this has led number of scientists, including myself. To actually question whether there isn't a better way to really have a unified approach to understanding brain function that will help explain?
08:44How we experience the mental features we experience in life and also that controls our behavior and so in my lab?
08:53Instead of starting with the categories and then asking well. Where are these categories in the brain or how is the brain creating? Where in the brain? Does it process emotion or cognition? We actually start with the brain structural and functional properties and then we ask OK well given our best understanding of how a brain is structured and how it works in a human body surrounded by other brains and bodies.
09:21Exactly what kind of minds can this brain produce.
09:26In different cultures.
09:27And what are the computational properties that can be used to understand mental life and so today. I want to introduce to you or talk to you just sketch for you, I guess the approach that we take which is a predictive processing approach, which I stumbled upon in 2010 because I was asked to review what what became a Seminole paper in the field, which was a fantastic paper in behavior and brain Sciences by.
09:58Andy Clark and the philosopher Andy Clark.
10:02This was my introduction to predictive coding an in order to review that paper. I had to go and read like 20 other papers because I had never actually heard of it. Before I mean in psychology. We've really even before in philosophy right there's a number of philosophers who talk about how prior experience is a lens through which we control action and construct experience can't said this.
10:32In psychology him hold said. This There are many times throughout the history of psychology where this idea has come about, but I was really impressed by the fact that.
10:44When I was reading neuroscience, neuroimaging work when I was reading work in anatomy and.
10:53Track tracing work in neuroanatomy when I was reading work in electrical engineering that Bears on the electrical functioning of the brain and in Physiology. These various different literatures were all pointing to the same insights. Even though they didn't weren't talking to each other, which I I just don't know another time in my scientific career over 25 years where that's ever happened. And so I'm going to talk to you about a couple of these insights today.
11:23And use some of the research from my lab to discuss these insights.
11:30And so.
11:32The first insight that comes from a predicted processing approach.
11:39Is that your brain actually is continually constructing concepts all the time and these concepts are? What control your actions and construct your experience.
11:55And so to explain how this works. I'm going to start from the brain's perspective, so I want us to take the brains perspective for a moment and so that we can understand really the brains Maine.
12:09You know puzzle that it has to solve is something that we can describe as a reverse inference problem.
12:15Or an inverse inference problem in the following sense.
12:19For your entire life, your brain is stuck in a dark silent box.
12:26Called your skull.
12:28And it learns what is going on in the world only by receiving scraps of information from the sensory channels of the body?
12:39Like the retina the Coclea and so on.
12:42These sensory changes that the brain receives are the effects.
12:50Of some causes in the world.
12:52But your brain doesn't know the cause, it only receives the effects.
12:57So it has to figure out what caused these sensory inputs, the sense data to know what to do about them, so that it can keep you alive and well.
13:08And.
13:09If we were evolutionary biologists, we would say to keep you alive and well so that you can do the most important thing.
13:19Which is eat chocolate?
13:22And also pass your jeans on to the next generation.
13:25It's hard to know sometimes which of those is more important?
13:30So any given sensory input, a flash of Light, a sound can have many, many, many different causes.
13:39At the same time.
13:41Your brain is also receiving sense input from your body.
13:45So from your brains perspective your body is another environment that it has to guess at the causes of the effects that it's receiving we call those effects into receptive inputs from the body, so an ache in your gut could be hunger. If you're sitting at the table dinner table at dinner time it could be waiting in the doctors office for test results so it could be anxiety. The same ache in your gut if you're a judge in a court room.
14:16Might be a feeling that the defendant can't be trusted. So, your brain us to determine the causes of these sense data, which are the effects so this is the classic kind of inverse or reverse inference problem.
14:31And So what does it do? How does it solve this problem it's trying to solve this problem from the moment that you're born until the moment that you die, So what is it using?
14:39And the answer is it has one other source of information and that is the past experiences that it has encoded.
14:48In the
14:51Connections between neurons.
14:54So, your brain has to remember past experiences that are similar to the present in some way in order to make a guess at what to do next to keep you alive and well.
15:10And I think the important thing here is that the brain when your brain receives sound or change in wavelengths of light and so on. It's not asking What is this is asking? What is this similar to? What is this similar to in my past experiences when the physical changes in the world and my body were similar to the present that is the sense data or similar to the present? What did I do next.
15:40Well, in psychology things that are similar to one another in their function is a category and a mental representation of a category is a concept.
15:51So you could say that what your brain is doing is it's constructing ad hoc concepts on the fly in order to make sense of sense data so that it can control your actions.
16:06So we all know that a category is a group of things that are similar in some way for example, a category of cats.
16:13Cats are similar in various ways.
16:16They have fur most of them that some they have 2 eyes. They have a nose, they've whiskers they?
16:24You know like to catch mice, most of the time.
16:33Now, what I just did I just give you a list of features that list of features is the mental representation of a cat that's called a concept, and in fact when psychologists study concepts. They ask people to give them a list of features that define the concept so for example, if I asked you to tell me what the prototype, the concept is for a bird? What would you say?
17:02Sorry.
17:04Right so, give me an example of a bird that has those features.
17:10A blue Jay a Crow OK now imagine that you were in pet store and I asked you to tell me what the prototype of a bird is what would you say?
17:22Sure, that's a feature but tell me give me give me the some of the features in an example, so what's the prototypical bird if your goal is to have a pet?
17:31Parakeet and what about if you're at the dinner table.
17:40The chick in an if it's Thanksgiving. It's a Turkey and if you live in South America. You wouldn't have said a Crow or a blue Jay you would have said a Peacock.
17:51So what's happening here, which what we just did is we just replicated an experiment from the 1980s. In cognitive science, where scientists discovered that the prototypes. The concepts that go with categories are highly variable there is variable as your blood pressure basic.
18:08Because what people are doing you don't have one concept stored in your head. One prototype your brain is making a prototype every single time in every context. For whatever function that category is serving right so we just talked about the category of eating a bird. The category of having a bird as a pet and we could talk about others as well.
18:29So we can do this with cats. If I asked you to list. The features of a cat and give me an example of a prototype of a cat you know you might say a tabby cat, but then if I said, well what about a cat who's good at catching mice well. What about a cat who is a good pet well. What about a cat who lives in a zoo and so on, So what your brain is doing is it's Taylor making concepts as you need them, which would actually dictate your action towards.
19:00The The The instance of the category in question right you wouldn't eat. A Parakeet and you wouldn't get well. Some people do keep chickens as pets. So I can actually use that as an example anymore. But maybe a Turkey. I can tell you turkeys are really annoying so you wouldn't keep we have wild turkeys where we live and they're very, very, very annoying. I mean, not as pets, but they just wander the street and terrorized people.
19:23So what I want to suggest you today is that this is the operating principle of the brain. So when I show you something like this.
19:32Your brain is just made a concept for cats and so when you see this you see it. You're more likely to see it as a cat because I just showed you a bunch of cats and so your brain is primed essentially to make an ad hoc.
19:46Category I ad hoc concept for cat so you see this as a cat as opposed to an Apple, which you might see it if we had just talked about fruit.
19:55And So what you experience in the moment is a combination of sensory information from the image an from the concept in your head.
20:04This is why Andy Clark likes to refer to conscious experience as a controlled hallucination.
20:11Now there are a couple of things about the way that our brains make concepts that set us up nicely to talk about predictive processing and here's one of them.
20:24So what is this?
20:26What do you see?
20:29You see something is playing a jump jump rope game, what's playing jump rope.
20:34Yeah, transformer? How many of you have ever seen an electrical tower in your life play jump rope.
20:40Well, I never.
20:42So right away but you're not recognized.
20:45Speaking so how did your brain do that? Well, this demonstrates one of the cognitive scientist called the most powerful capacity of a mind? Which is to do conceptual combination your brain takes bits and pieces of the past and combine them in new ways, so that you can make a concept, and understand burgers is.
21:06Now let's just look at it for a minute.
21:11Many of you.
21:15And feel the pounding of the the transformer tower when it lands.
21:24I'm not sure it works in this space, but how many you can hear it jumping.
21:29Yeah, I seen this probably 500 times and it never goes away.
21:34And this is the other really important thing about concepts.
21:38Concepts are not these abstract a modal propositional things they are in body.
21:48When your brain is making a concept.
21:50It's actually.
21:52Doing something really remarkable it's changing the firing of its own sensory neurons.
21:58Based on what you see your brain is changing the firing up your own sensory neurons, so that you feel. Some somatosensory impact and you also.
22:09I hear some people come here actually the jumping of the tower. How many of you have ever had a song going through your head that you can't get rid of.
22:25Here's just one study from my lab.
22:28Where we verified this effect, so here what you're looking at are 2 brains one in the medial view one in the lateral view. Just sliced in a bit so you can see the insular lobe. I'm assuming everyone here knows how to find their way around a brain so I'm not going to Orient. You and what subjects were doing here is that they were lying still in this. I'm so they were asked to basically create a set of concepts. And here's what we see despite the fact that subjects are lying completely still in the scanner.
22:59We see massive activities in Motor Cortex Somatosensory Cortex Premotor Cortex and Supplementary Motor Cortex. Despite the fact that their eyes are closed. We see massive changes in activity in V1.
23:12An early Visual Cortex.
23:16This is the mid posterior insula, which is considered primary interoceptive cortex or visceral. Visceral sensory cortex, so despite the fact that subjects were not moving the regions that represent changes in the interior of the body, the internal milieu from changes in heart, beating an in lungs expanding basically anything to do with the autonomic nervous system changes in metabolism changes in immune function and so on.
23:49We see changes in the representation of sensory inputs to the body and most interesting. Lee even though subjects are completely. Still, you see increases in activity in the hypothalamus all the way down through the NTS, which are the regions which are the matrix of nuclei, which control the internal Millia. The systems of the internal milieu. Autonomic nervous system and so on, and so forth and that's just from lying and listening to words.
24:24Now.
24:25When your brain can't make a concept.
24:28That's right for the situation you are experientially blind.
24:34Presumably, like right now.
24:36Unless you've seen me give this talk before and you've seen this image. What's probably happening for you right now is that you know your billions of your neurons are attempting to make sense of this black and White Blobby image so that you see something other than black and white blobs.
24:53And your brain is basically searching through your lifetime of past experience asking the question. What is this similar to What is this similar to my past experience?
25:05Figuratively, speaking right the last time that my time that my body was in this situation and in this state in this room or in a room like this, or at a talk like this? What visual visual sense data mean?
25:22And then what do I do next?
25:25So how many of you actually see an object here.
25:29Yeah, what do you see?
25:36A Monster.
25:40Nice anybody else.
25:43Western Western Europe are you now I'm going to so for you, your your brains are attempting to deal with this experiential blindness. So now I'm going to cure you of your experiential blindness actually when I when I'm in medical audiences. I usually like to kind of get up in front and go.
26:02I'm going to.
26:04Are you ready to be cured?
26:13Much better now can we have that Amen.
26:25Right.
26:29OK, now how many of you CAB.
26:32Or at least part of the be yeah.
26:35Because now when your brain is searching through past experience. There is new information there from that color photograph.
26:42And this knowledge changes how you experience these blobs. So, your brain is actually constructing an image of a B, even though there is no image of be present, hence the idea of a controlled hallucination.
26:54An and of course, there are people here, including Phil, who study actual clinical hallucinations, but things kind of work the same way so this hallucination is what I am calling a concept, and in a moment I will show you that this is actually what neuroscientists call a prediction, which is business as usual for your brain.
27:19Because these this input from your brain.
27:23The is necessary for you to have anything other than experiential blindness.
27:32It's what's required for you to hear the words coming out of my mouth and have them make sense to you right if you were not a native speaker of English or someone who was exposed to English and he would learn the language what you would be hearing is a bunch of noise. I mean, some of you may still feel like you're doing a bunch of noise, but
27:51That was a funny joke.
28:00Have to have a concept to be able to hear heavy metal as music.
28:06I had to learn that.
28:08My daughter is a heavy metal drummer.
28:12And so on, and so forth, but in order for the sense data to make contact with your guide your actions your brain has to be able to make make meaning make a concept of what those sense data mean?
28:26So the inside here is that?
28:30Psychological phenomena like what you would find in the table of contents in a intro. Psych book and the kinds of phenomena that you deal with with your patients are made with concepts. You are your concepts. So I'm not saying that your brain deliberately makes concepts, although sometimes it does, I'm saying, You are the concepts that your brain makes your mind is the concepts that your brain makes your concepts become your actions and the contents of your experience.
29:00And that sets us up nicely for the second insight, which is that this whole production happens productively.
29:09In psychology.
29:11We have a model of the mind really that comes to us from Physiology experiments of the 19 century.
29:20That the mind is the mind or the brain is dormant that it's stimulated by stuff in the world and then we react. We might do some cognition. Or maybe some emotion, they might battle with each other for control of behavior and then we make a response.
29:35That's not a straw man that is really the dominant paradigm still actually in psychology, and actually that is the basis of a lot of the treatments that we use.
29:46But your brain is not wired to react your brain is actually anatomically wired to predict.
29:55You are walking around with a brain that is loaded with bits and pieces of your past and your brain is using that to predict your immediate future, including what is going on in your own body with ad hoc concepts? Which ultimately become the experience and actions of the present this is what scientists call running an internal model of the world. Actually, your brain is running a model of your own body in the world.
30:24And these ad hoc concepts predict incoming sensory inputs, and motor changes.
30:30They represent the causal relationships between the events in the world and the body as they are right now and the sensory and motor consequences in a moment from now and again the best available evidence now from thousands of studies across more than 5 research domains is that this is the best guess about how your brain navigates the world and constructs your experience.
30:54So again here is an intuition here's an example to give you an intuition.
30:59Let's all do it together.
31:02Once apona.
31:07In a magical Kingdom.
31:10Far far.
31:14There lived a beautiful.
31:28That's a drag Queen superhero by the way.
31:32OK.
31:34This is a really nice example of prediction right. The fact that we've all been exposed to in this room to most of us to fairy tales and they all pretty much begin in the same way. And so our brains are able to predict exactly.
31:52What will come next just like right now you're listening to words come out of my mouth and to you it seems like you're just reacting to the words, I say, but actually your brain is making predictions about every single sound that escapes my.
32:13Mouth right lips, yeah, and it would be really funny. If I had mentioned some other part of my body that you were not expecting. That's what we would call prediction error. Now there are well over at this point, I would say, well over 500 papers closer to 1000 papers that we've been able to identify across multiple domains of research which actually support predictive coding and none of you most of you don't know me very well so you don't.
32:45Except one person alley.
32:48Ellie you can attest to the fact that I'm very critical person right. Yes, how are you I just believe what I read?
32:54So I guess my problem. Thank you point is that whatever about to tell you is not of course. Everything is still a hypothesis but but I was really surprised by the I am still continually surprised by the extent to which the data tend to support this view normally.
33:25What I do now is I just show you a cacophony of examples of these papers just to make the point that this is like an avalanche of research across many different research domains, but I'm just going to sort of show you the most important ones.
33:39Whoops I really wanted to show you I just pulled these from fills I think it's going to there, we go.
33:46Yeah.
33:49Yeah, so I should I should say I'm not just showing you feels papers. Uh because he's the one who invited me. I actually fills papers are a staple in my lab because it's some of the most really impressive work. Of course, probably in psychiatry. People are interested in this because of the topic, but from our perspective we are interested in this because this work constitutes really some of the best empirical evidence for predictive coding.
34:20In the brain.
34:22And when you take this work along with the work in electrical engineering and the work in Physiology and the work in track tracing studies of Anatomy and in brain imaging and so on what you get is a coherent. Neurobiologically inspired research program for understanding the human mind and human behavior.
34:42Which Unites?
34:44All of the social brain and the emotional brain and the cognitive brain and so on into a single brain.
34:52Now this single brain.
34:55Is expensive?
34:57You may have thought you that you were a frugal person, but you have a very expensive brain your brain cost 20% of your metabolic budget.
35:07Unlike say a chimp it when you compare chimpanzee for example, whose brain costs about 99 or 10% and 70% of this metabolic budget.
35:19Is is dedicated to Watt neuroscientists call intrinsic activity? Which means activity in neurons that is not due to being prompted by a stimulus from the outside world.
35:37So largely this activity is about predictions, which means 14% of your metabolic budget 14% of the oxygen used 14% of the glucose used goes to maintaining your internal model of the world, which are these predictions for what we would call them. Concepts ad hoc concepts. And so generic just really sort of simple simple here is like a simplified explanation.
36:07Just going to show you in cartoons 1st and then I'm going to show you on the brain.
36:12This is how this is the hypothesis the general hypothesis for predictive coding.
36:18That you have a brain that's largely talking to itself.
36:22Your brain starts with initial conditions as they internal model of the representation of what's going on in the world and what's going on inside your own body.
36:33And then IT projects itself forward in time, creating ad hoc concepts based on functional similarity or you could say creating a prediction about what the body has to do next.
36:44So these would be the motor actions and the visceral motor actions, which have to support those motor actions.
36:54And these commands also create the predicted sensory consequences of those actions, so in effect. The brain is asking itself well. The last time I was in this situation and I prepared to make this action? What did I see what did I hear? What did I feel, and so on.
37:11In those predictions actually change the firing of sensory systems, so that we have this these simulations that we experienced earlier with the examples.
37:26And then
37:29Sense data comes from the world.
37:33And there are comparisons.
37:36And if the comparisons indicate that there is a pretty good match.
37:42They confirm the predictions.
37:44Then that means the sensory inputs were made meaningful to guide your actions and create your experience and we call this categorization.
37:56So predictions are like Anticipo Tori.
38:00Guesses or anticipo Tori opportunities for categorization that are then confirmed by the sense data in the world and the really interesting thing is that if it's the case that your prediction largely is confirmed by the sense data from your body and from the world then.
38:20The there's not that much change in information from the world doesn't make it very far into your brain after that because basically the neurons are already firing in a way to capture the sense data from the world.
38:37Oops. Sorry I hit the wrong slide.
38:42However.
38:43It might also happen that there is information that we in the sense data that we didn't anticipate.
38:52We call that prediction error and so this is what happens is the brain than has the opportunity to modify its internal model that is, we have a fancy name for this in psychology. We call it learning so the brain can learn information learn new sense data so that it can predict better next time.
39:19And this is general this is the generic idea of how light becomes vision and chemicals in the world becomes smells and how the interceptive sensations in your body become affective feelings that we used to build emotions.
39:37So this is how an ache in your chest. The exact same ache in your chest might be loneliness.
39:45It might be anxiety.
39:48Or it might be the beginnings of a heart attack.
39:53Not a joke that's actually not a joke.
39:56Which I can talk about later?
39:58So.
40:00If we're going to put this on the brain.
40:02And you know what I'm showing you here again is sort of.
40:07Backed up by.
40:09About.
40:13As well as a couple of examples. I'm going to show you in a minute. So here what I've done is I've just.
40:20Put.
40:22I've taken
40:27Anna colored some regions to make a point, which is the regions that are evidence. Strong evidence that they initiate the cascade of predictions that will become your ad hoc concepts are colored in blue. The Red Strip is your motor strip and yellow are colored 3 primary sensory regions just for Illustration V1.
40:57S1 so primary Visual Cortex Primary Somatosensory Cortex and primary interoceptive cortex. And so the idea is that when your brain projects itself into the future what it's doing is it's making a first, a set of visceral motor predictions to control your autonomic nervous system your immune system your endocrine system and so on.
41:21And then
41:25Those regions make a prediction to Motor Cortex, an motor cortex also sends a actually the motor system sends a set of predictions to your skeletal motor system and those are the motor predictions that which come first.
41:40And I'll show you why we believe this in the next couple of minutes.
41:47And then copies of those motor predictions and bitter motor predictions are then sent to the primary sensory regions.
41:57So it's this constant cascade of prediction.
42:04And then a constant cascade of sense data, which comes from the body an from the world to constrain those predictions to confirm them or 2.
42:17To change them.
42:19So traditional experiments.
42:22An traditional treatments to some extent, which are are pretty much designed on a model of the brain, which goes like this we have, we stimulate the subject in some way then something goes on inside their head like they make evaluations, which we could describe as cognitive or emotional and then there's a response and actually what we do is we give sets of trials in experiments where we presented stimulus.
42:55And then we measure, the response presented stimulus measure. The response to trials are randomized, so that we can aggregate them in statistical analysis. And so basically the brain's predictions are going to be wrong. Almost all the time because we've set the experiment up that way. And so basically what we're doing is forcing the brain into a mode where it favors encoding and processing of prediction error, which are driven by the stimuli that we present.
43:25When in the real world, the real world dynamics of the brain probably work more in a temporally continuous way where the brain is a system. An it's dynamically moving from one state. One part of its state space to another or for today. Will say one state to another.
43:47Ann.
43:49Actually and then is constrained by by sense data from the world and from the body and psychopathology can be understood a range of different psychopathologies different diagnostic categories, which are kind of like the folk psychology categories. Psychology are diagnostic categories are also folk psychology categories are full categories to some extent, there ways that we categorize symptoms.
44:18But it's possible to have a framework where we can understand particular types of symptoms as problems with the internal model problems with processing of prediction error, either with the the ability to encode the prediction error, the ability to the precision or reliability of that error and so on, and so forth.
44:45And so here's an example of just one kind of study and I've picked a study which sort of supports the idea of predict if this predictive coding model that we've come up with and I should say I should have said this before that, the schematic that I just showed you is based on mostly actually on track. Tracing evidence from Helen Barvis is where we'll go over again in a minute.
45:12But there's
45:14You know there are lots and lots of different predictive coding models. The one that we use is kind of a whole brain model. We also have worked in the cerebellum and also the hippocampus which I'm happy to talk about. But in an hour long talk. You can't cover everything so I'm just going to focus on the Cortex and here's one really nice example of a study that supports this view, which comes from the animal literature that has nothing to do with prediction, meaning this is these are not. People who set out to study prediction instead.
45:45What they were studying was vision?
45:48And.
45:50They trained rodents to run on a wheel.
45:56And while that wrote it was running on a wheel. They recorded from single cells single neurons in various parts of the brain, including V1, so the animals running on the wheel. You record from V1, you get the pattern of activity. That represents the animals visual sensations, while it's running on the wheel.
46:19Then.
46:21You a blade the retinas of the animals so you blind them.
46:27And then you measure their neural activity for 48 hours.
46:33And what you find is that V1 neurons quieten down initially 'cause they're not receiving any sense data from the periphery.
46:41And then they very quickly over 48 hours ramp up back to normal firing rates.
46:48And then you stick the rap the rats back on the wheel.
46:53And you measure their neural firing in V1 and you find.
46:58It's pretty much identical to what it was before.
47:02When they were cited.
47:05But you're also measuring from other neurons in other parts of the brain so you can figure out what is driving those V1 neurons now that there is no visual input from the retina to the thalamus 2V one. So where is this activity coming from?
47:24And the answer.
47:26Is?
47:28This singulate cortex.
47:33The Singulate Cortex.
47:37Is driving V1 neurons?
47:41When the rat is blind in order to create visual representations BC.
47:47Hum.
47:48This is what we I just called a prediction.
47:57Now the singular.
47:59In this study, the single it was described this, this sort of.
48:07But sometimes called the doors are serious cigarette or the anterior move was described as a A Mover Association area in which it is the Motor Association.
48:17It's also.
48:19A primary control region for regulating your autonomic nervous system and your immune system annuar entropy system. It's a primary regulator. The hypothalamus and all the nuclei all the way down into the spinal cord.
48:39And that's a really important insight.
48:42Because as I'm going to show you because it turns out that these regions are are really important for issuing predictions along with the hippocampus.
48:55So that's just one study from from a mountain of studies, which suggest.
49:03That the brain is working predictably and.
49:09Basically, what this means is that we have to really kind of change our understanding of what is stimulus and a response are right? A stimulus is merely perturbing a bunch of intrinsic activity that's going on in your brain right now, so right now. This stimulus is are my words and my actions and that is not causing things to happen in your brain. It's actually just perturbing the trajectory of activity that's already there.
49:37So if you came to this talk full of caffeine and presumably dopamine and you had a really good breakfast and he slept really well last night, you're probably thinking.
49:50And if you skip breakfast.
49:53Are you didn't sleep well last night you're probably.
50:02But it also suggests.
50:05As I've shown you just giving you a hint of arte stuff.
50:09Yeah, that.
50:12At this end.
50:14Body is
50:16Ability to
50:17What the hell does that mean well here is really what it means if you?
50:24And this, I would say probably is the big takeaway from this talk if there's one thing that you remember, hopefully it's this your brain did not evolve for you to think and feel and see your brain evolved. This is work on developmental an evolutionary neuroscience your brain involved involved for rationality. It didn't involve for accurate perception your brain evolved to control your body efficiently.
50:54That's why brains evolved sensation and perception an experience in at are all in the service of action there in the service of regulating the body.
51:06This is
51:10In evolutionary and developmental neuroscience pretty much a given and it's backed up by a lot of.
51:20Research, including research from this fantastic book called the principles of neural design. We are I took this quote the core task of all brains is to regulate and organisms. Internal milu by anticipating the needs of the body and preparing to meet those needs before they arise.
51:39Physiologist in many neuroscientists already know this.
51:43You can think about your brain as running a budget for your body. It's not budgeting money. It's budgeting glucose and water and oxygen and so on. We give this the fancy name of Allostasis because it's not doing this reactively. It's doing it. Predictably, it's just metabolically more efficient to have a predicting brain if you don't predict very well it's much more metabolically inefficient.
52:16And for example, autism is seen as a problem with with prediction an interception, which are this is the sense data arising from this body budgeting from Alice thesis is what we call interoception and so some of the findings. I'm going to show you today. Next will show you will suggest that metabolism and energy regulation and the sensory consequences of those are at the core of all mental activity, not just emotion. But every waking moment of your life.
52:47When you're thinking when you're perceiving when you're deciding and so on.
52:53Representations of what you do ultimately give rise to what you See and what you hear and what you feel, and even your sense of self.
53:01So here's what I've done is I've just taken the Broadman areas on the lateral surface. The medial surface and the insula and what I've done is I've colored them, according to you. About 30 years of tracked raising research so this is research where you place a referee.
53:20Freezer in one part of the brain, then you watch it spread and what I've done is like you know if you take the cortical sheet.
53:29Oh, I'm sorry if you.
53:34What did I say about I can't talk and yet?
53:38Is that it OK if you take the cortical sheet off?
53:43The rest of the brain and you stretch it out like a napkin. You will see that the neurons are arrayed in layers. That's what it makes that's what makes it a cortex.
53:52And some layers have 4 layer some parts of the record except for layers. Some have 5. Some have 6. Basically, the parts that have 4 are the parts that originate with along with the hippocampus originate predictions. In the brain that make that initial volley of predictions and those are colored in light to medium. Gray here and so this is based on you know, mostly work in macaques, but also in other.
54:23Mammals as well.
54:25Predictions go from light Gray to black regions. That's how they propagate out and prediction error goes from black to the light Gray along the Cortex along that cortical gradient.
54:40So these regions we refer to them as a granular ordis granular cortex, but they have another name does anyone know the name.
54:50What is the mid singulate?
54:54Limbic their limbic.
54:58Are you shocked you should be shocked because limbic regions? Are the most powerful predicting regions in the brain?
55:10Along with the hippocampus which was included in the so-called mythical limbic system. This suggests hypothesis that that concepts and predictions originate concepts, as predictions originate in the parts of the brain that for.
55:28Centuries was considered to be the most reactive part of the brain. The home of motion. People still write about this. These regions as if they are emotional regions. They're not emotional regions. Their regions of the brain that controls the body and as a consequence, they are at the Top of the anatomical hierarchy prediction hierarchy in the brain.
55:48So they're supposed to be the home of your inner beast, which is most reactive to things in the world. But in fact, and in need of control. But in fact, these regions are driving perception and action throughout the brain.
56:01An actually if you seed those if you do something called a resting state study where you have subjects just lying in the scanner with their eyes open or closed and they're not they're asked to keep their mind clear and you seed. The limbic regions and you look for places where there connected and So what we did is we?
56:31We actually verified anatomical connections between these regions and then we did this resting state analysis with.
56:42Actually, over 700 subjects so we split this sample in half and we used half as a discovery sample half is a test sample attest. Yeah, test sample and then we look to see for each limbic each part of limbic cortex. Watt were the areas that gave us that what were the areas that had voxels or parts of the brain that whose time course correlated the signals correlated with those seed regions the.
57:17The limbic regions that we seated and if we had more time I go over the findings. More with you. But we basically seated all along the single it and we see did the anterior insula, which is a granular and what we recovered were one. Discovery map of like all the voxels in the brain, which are coral whose time courses correlated stay with the anterior insula and we had this for every single region, we seated. We had a discovery map and then we did.
57:47A cluster analysis and we found 2 networks that overlap in a set of rich club hubs very, very connected hubs in the brain and here they are, and actually some of you will be familiar with these networks. This is the default mode network and the salience network, which are considered to be resting state or intrinsic networks that reflect the large scale wiring in the brain and they actually overlap in a set of rich club hubs that have been identified in connectomics research all of the limbic tissue in your brain.
58:18Is in those 2 networks?
58:21The other thing which was interesting was that we found that the posterior insula mid posterior insula is also a hub that connects these networks this is.
58:37The region that is representing sense data from the internal milieu of your body.
58:46Now, for most of you well, I see it this way interception intercept if information is always with you all the time it's part of every representation your brain makes whether your emotional not whether you're aware of it or not, and most of the time you're not aware of it. Most of the time we don't experience in teh receptive sensations, as physical sensations were not really wired to experience the world. That way ourselves in the world that way. If we were we would never pay attention to anything outside our own skin ever again. 'cause there's a lot of drama going on right now, you guys are sitting there really quietly but.
59:21The whole orchestra of things happening inside your own body that you're unaware of.
59:26Instead we experience.
59:29We access affect we access into receptive information as affect.
59:36As feeling pleasant or feeling unpleasant as feeling worked up or feeling calm. These experiences of of affect our features of consciousness like lightness and darkness and so on, there, not emotions. They are properties of consciousness that are always with you whether you are in an event that we would call a perception or a thought.
01:00:03So they're kind of like barometers for how Alice statically how your body is doing.
01:00:11And the brain system that seeds predictions also.
01:00:18As I just want to show you also regulates the body, so these again. The blobs are connectivity. Here, not activity. So there connect they reflect connections between regions and hear what we've done is we've taken the default mode network and the salience network just the limbic portions of those networks and projected them into the volume of this image. Ng study with 700 plus subjects and what you can see is that?
01:00:49These cortical regions actually have projections connectivity that we verified with Amtrak, tracing projections in macaques. All the way down through this matrix of Regions in the brain stem, which control your body that maintain allostasis.
01:01:09So.
01:01:11This is what your brain is always doing regardless of whether you experience yourself as having a thought or or perception or an emotion your brain is always controlling your body?
01:01:23Here's just a sampling of studies that these are mainly activation studies that look at for default mode that have shown activity in default mode during tasks an not just during rest, but also during tasks.
01:01:40So when you're affiliating socially when you're experiencing chronic pain when you're doing a reward based task and so on, and so forth.
01:01:49When you're making decisions when you're creating perceptions basically whenever you see this activity your brain is regulating your body even though you yourself may not be experiencing it.
01:02:03An our hypothesis is that default mode activity is really about is really concerned with the predictions that creating the predictions that become your experience.
01:02:17These regions also.
01:02:19Control the bed nuclei of the.
01:02:26That give rise to the neuromodulators, which we think of as attentional so regions that are part of the default mode that our limbic actually and also part of salience so this is more salience.
01:02:46And this is more default mode.
01:02:49This is more default mode, these limbic regions also control the bed nuclei for Norepinephrine Serotonin and dopamine.
01:03:01And to me what's really interesting about this so that means that these are the neuromodulators that are considered to be important for regulating attention. The attention of matrix in the brain so that suggests that these regions are not just important for generating predictions. They also should be important for determining which prediction errors. You will pay attention to and which ones you won't and was really interesting to me is that we have this reading groups. You guys might know this because your physicians. Many of you but we didn't know this.
01:03:32Dopamine and Serotonin.
01:03:35Actually, there's whole literatures on these neuromodulators and they're important for regulating metabolism.
01:03:43Serotonin for example, is a neurotransmitter that allows the brain to spend its resource is when there is no there's no immediate reward insight. It's basically allowing a brain to forage or explore to learn prediction errors right? What are the 2 most expensive things your brain can do it can move your body?
01:04:10And it can learn something new.
01:04:14And you need serotonin to be able to do those things.
01:04:18And so you can start thinking about for example, what SSR eyes might be doing to a patient who has who's depressed.
01:04:26And how it might help initially but how it might stop helping at a certain point, and might even contribute to the ongoing to an ongoing symptom picture if depression is at its base is a metabolic disorder.
01:04:44Similarly, dopamine is not a reward neurotransmitter. There is a massive amounts of evidence at this point that dopamine is really important for effort for any kind of effort. Anytime you're going to spend basically any kind of cognitive effort any kind of any kind of processing effort. Any kind of physical effort. Dopamine is involved and over mean there's a whole literature on it's important in regulating metabolism.
01:05:13So, in a very real sense your body is part of your mind.
01:05:20You have a mind because you have a body your brain is always maintaining allostasis and therefore it's always doing in representing the state of the body doing interception and it's always attempting to create concepts to make sense of your body in relation to what is going on around you?
01:05:40And in this way.
01:05:45A body bodies function is always important to mental events, even when.
01:05:52Even when we're not aware of it, even during cold cognitive so called cold cognitive states.
01:05:58So I'm just going to wrap up now and say.
01:06:02From from my perspective.
01:06:07It's
01:06:08Useful to think about the combination of prediction and prediction error as a framework for understanding mental life and also understanding what goes wrong with mental life and to some extent, you know in our lab. We're now thinking about depression and anxiety. You know along with the construction of emotion, and other phenomena in this way. And if I had more time I was going to prepare to talk to you, a little bit about the metabolic SUV.
01:06:38Brain function because that's where our work is going looking at the ways in which encoding prediction error. That is learning something new. That isn't in your in already in your internal model learning to make new concepts as it were is a metabolically costly.
01:06:58Activity that not every brain can do.
01:07:03But the I will just leave you with this.
01:07:06This idea at the end, which is that this predictive coding approach really dissolves the false boundary between the body and the mind.
01:07:17Between the mental and the physical not in some ghazi mystical way. But in a really concrete scientific way, and that means that many of the illnesses that we think of as mental like depression may have a basic may have basic biological similarities to other phenomena that we think of as mainly physical diseases like diabetes.
01:07:45Right.
01:07:46So what I'm not suggesting here is a diabetes causes depression or the depression causes diabetes. But I'm I'm suggesting that there's a common metabolic there. A common set of metabolic concerns that the brain has and when those metabolic concerns are disrupted.
01:08:02That leaves patients that leaves us vulnerable to lots of diseases that are highly comorbid in ways that we don't understand. But actually if we took this kind of an approach it might shed some light on the ways in which why there comorbid. It's not because one is causing the other. It's because they actually have a common set of underlying causes and with that I will.
01:08:26Thank you for your attention.
01:08:29And also thank my fantastic lab who will show up in a minute who actually do all the heavy lifting in my in my lab. Thank you very much.