How Dopamine & Serotonin Shape Decisions, Motivation & Learning | Dr. Read Montague

If any goal that you achieved, whatever it is, taking a drug, eating a food, u getting a a partner or whatnot, um if that was enough for you, right, then you wouldn't keep living. You want that system to keep tracking and once it gets to one place, you want it to have another place to which it could go. Otherwise, you wouldn't live. Welcome to the Huberman Lab podcast where we discuss science and science-based tools for everyday life. I'm Andrew Huberman and I'm a professor of neurobiology and opthalmology at Stamford School of Medicine. My guest today is Dr. Reed Montigue. Dr. Reed Montigue is the director of the center for human neuroscience research at Virginia Tech. He is also an expert in the science of motivation, decision-making, and learning, and a pioneer in developing methods to directly measure levels of dopamine and other neurom modulators in humans in real time. Today, you'll learn how dopamine really works. Not just to regulate your levels of motivation. We've all heard that before. But also to teach you things. Dopamine is involved in learning as well as persistence or lack of persistence. As Reed will teach you, most of what we hear and know about dopamine is based on the idea that dopamine levels go up or down depending on our levels of expectations and then what happens. But as he explains, most aspects of life, work, school, relationships, our pursuit of money, etc. involve multiple milestones. We work, we wait, then we get an outcome that in turn informs the thing we do next. Or maybe dopamine arrives suddenly with no work involved at all. In other words, dopamine levels are constantly changing and that shapes not just what you do now, but how you think about your recent past and what you will do next. So when we say dopamine is involved in learning, today you are going to realize that dopamine is teaching you how to adjust your behavior. We of course discuss how this knowledge can be leveraged for better motivation and decision-making, even better social interactions. And we also discuss serotonin and how dopamine and serotonin work in sort of seessaw fashion and how serotonin in particular teaches you about unwanted outcomes. We also have a discussion about SSRIs that you're going to find fascinating. As Reed points out, SSRIs increase levels of serotonin, but often that serotonin gets used at the dopamine synapses to reduce the rewarding properties of dopamine. So today's discussion about dopamine and serotonin is going to be vastly different than any that you've heard or read about elsewhere. You're going to learn how those neurom modulators work, and you're going to learn how they impact your everyday life and decision-making. As we all know, discussions about dopamine and serotonin are everywhere nowadays. But in today's episode, you're going to learn from a top expert in the field what these molecules truly do. And that's going to help you better leverage your efforts, introduce what we call deliberate delays, and how to use tools like AI to improve your levels of motivation and your ability to learn through neuroplasticity. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is however part of my desire and effort to bring zerocost to consumer information about science and science related tools to the general public. In keeping with that theme, today's episode does include sponsors. And now for my discussion with Dr. for Reed Montigue. Dr. Reed Montigue, great to see you after all these 15 years. 15 years. Um, you turned us down for a job offer then. I did. Um, but we both turned out okay. So, well, I hope so. We'll see. Well, you certainly turned out okay and uh you look great. It's always great to see a colleague looking so fit and healthy who also raised five children successfully and uh all those things. We'll talk a little bit about your life and maybe uh your athletic life a little bit later, but I want to talk about dopamine. The world is obsessed with dopamine. Now, until very recently, people thought about dopamine as a reward. Now, slowly, people are starting to understand that dopamine is involved with things other than feeling good um such as motivation, movement, etc. How do you think about dopamine the neurom modulator and then we'll move into the context in which you study dopamine but when somebody says what does dopamine do how do you think and respond to that question well it used to be that dopamine was thought to equal pleasure dopamine goes up you feel good dopamine goes down you feel less good okay there's been an explosion of work on it most of the new work that's not psychological has been out of the artificial intelligence world what's now called artificial intelligence. Um it's very clearly a learning signal number one. So dopamine fluctuations high and low control learning. It's also playing multiple roles. It plays a role in motivation and it may also play a role in the way you feel. Okay. It's it's less well understood how the sort of mechanics of what dopamine does for changing your nervous system relates to your feeling state. you can have a feeling state that's good and see things um that don't correlate with dopamine being the cause of it. Uh let's talk about dopamine in the context of learning because that's something that I think most people don't associate with dopamine. Um what are a few examples of what we know about dopamine and its role in learning? That's a world I can't even summarize in a quick way. Uh people that work on rodents now will um take a genetically modified rodent and they will study the way in which dopamine release correlates with something the animal is learning. The animal may learn to turn left when it sees a light. It may learn to run toward food. It may learn to run down a maze. All kinds of learning tasks associated with the animal are associated with dopamine fluctuations in your brain. Now these aren't global. They're all over the place, but there are different kinds of signals that you can find in different spots in your brain. Um, and we've begun to understand dopamine as a central player in the algorithms that your brain runs. And that's where people like me, um, and people like me, computational neuroscientists, have made a connection. And that's the connection between the kinds of learning rules and learning procedures that are installed in your brain and installed in the brain of every mobile creature on the planet and dopamine fluctuations. So that's a that's a strong connection that has been worked out over the last 30 years. The algorithms are well understood. What wasn't well understood 30 years ago was the kind of remarkable things those same algorithms can learn. I'll come back to that. I mean, there have been a bunch of modern breakthroughs in what's called reinforcement learning. And reinforcement learning's main biology partner is dopamine. It's the first big hit. Now, you know, it's a area of science. And so, what happens when you have a a big finding that looks like it explains a lot of things? Well, you know, people come rushing in to sort of beat it up. That's their job. That's their job to hack away. Oh, is it really this? Does it work the same in this context and that context? Um but I think the um description of what dopamine does as a learning rule is pretty much true. Let me give you an example. Um so psychologists since the time of Pavlov have understood what it means for an animal to generate a prediction and to compare it to an outcome. Okay, let let me the example is so today's Wednesday. Suppose and this is Rich Sutton's example. Suppose I make a prediction today that it's going to rain two inches on Saturday. Okay. Now, we're going to fast forward to tomorrow and I'm going to update my prediction because I have new knowledge and it's going to say I'm it's going to rain 10 inches on Saturday. Okay. There's been no reinforcing feedback. It hasn't rained yet because it's now Saturday yet. I'm making a prediction about Saturday. But there's a difference between this expectation and that expectation. Those differences are encoded by dopamine. It's called a the temporal difference error. Um, and dopamine seems to code that before you ever get to the terminal return. Imagine that you were playing a game like checkers. You make a move in the game and you might make, I don't know, 40 moves before you win the game. And suppose winning the game is the reward. Well, you may have some prediction. Your brain makes a prediction when you play board position to board position that you're going to win the game. And that's a fluctuating quantity. That's a different kind of learning rule. The kind of learning rule that psychologists talk about that you think about in your everyday life is it's going to rain two inches today. Okay, how much did it rain? Okay, so that's a comparison between an outcome and your expectation. What Rich Sutton and Andy Barto did was said, well, what you really want to do is you want to stick between there your next prediction. So you want successive predictions. Okay. And why is that a good model for animals? Well, because if you're an animal and you're wandering around foraging, um, mainly you're not finding anything. You're going from position to position to position to position position, but you're learning and dopamine is encoding those signals. I'm so glad you said the word foraging because I want to hover on the theme of foraging uh, in the context of human decision-m and learning and behavior. So to stay with uh your description, Saturday rolls around. Let's say it doesn't rain. Let's say the person doesn't want it to rain. They're not a farmer. Uh they want to go to the beach on Saturday. Now we can talk about reward prediction error, right? The difference between the expectation when it actually happens. Okay, let me let me interrupt and correct that a bit. The reward prediction error that people talk about dopamine representing is the prediction error that you get for every single step whether or not you've received reward. That's kind of diffused out in the psychology literature as you have an expectation and you have a reward. It may be positive, negative or zero. And what you do is you make an error there. That was understood in the 60s and 70s. It's called the Rcoro Wagner rule um 1972. That's how the system should learn. The fact is though that doesn't model reality very well. Reality doesn't give you feedback like that every time. Reality often gives you long stretches of nothing. The insight I think of Sutton and Barto in their algorithm was well a better algorithm for learning continuously is to take successive predictions and to say that's a learning rule. Obviously it's a learning rule of the outcome when you get an outcome when it's not zero. But it's successive predictions. It's like why that should be such a deep idea is not clear to me. What is clear to me from data is an algorithm based on that is installed in Bbrains, C slug brains all the way up to human brains. There are these temporal difference reward prediction errors. And um so I guess I'm sitting here trying to backwash the old version of it which is people say in a kind of uh vernacular way oh it's the difference between your expectations and the reward. Um yes when that happens but most of the time that's not happening in which case it's the it's the ongoing difference between your expectation and your next expectation. So it's fluctuations in your expectation as you move through the world. the Deep Mind guys in London who beat the world go playing champion and made Alpha Fold and won Nobel prizes and I mean they're starting in 2015 they just had this unbelievable series of hits. They used the Sutton and Barto algorithm. They trained those systems where uh people would make the players computer players would make hundreds of board position changes before you ever got to the end of the game. and update and learn based on that. They threw other tricks into I'm not going to get technical about it. So there's a difference. It's not just expectation and outcome. It's expectation next expectation current outcome and that is what rolls through and that is what we see installed in we have a paper uh this week coming out on honeybee brains where you can show the same sorts of learning rules in honeybee brains. uh in honeybee brains it's probably octopamine not dopamine. Um but the other thing to say about dopamine is it's not just dopamine. It's very clear that lots of neurom modulators like that are fluctuating with learning and motivation and probably the whole symphony of them that creates motivation states and things like that. I'd like to take a quick break to acknowledge one of our sponsors, David. David makes protein bars unlike any other. Their newest bar, the Bronze Bar, has 20 grams of protein, only 150 calories, and zero grams of sugar. I have to say, these are the best tasting protein bars I've ever had, and I've tried a lot of protein bars over the years. These new David bars have a marshmallow base and they're covered in chocolate coating and they're absolutely incredible. I of course eat regular whole foods. I eat meat, chicken, fish, eggs, fruits, vegetables, etc. But I also make it a point to eat one or two David bars per day as a snack, which makes it easy to hit my protein goal of 1 gram of protein per pound of body weight. 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So, I want to pin up a a few rules uh so that um people can move along this because I think um most people and including me who learned about dopamine through you know neuroscience textbooks and lectures and um papers and so forth um have been fed this overly simplistic model of expectation versus reward or lack of reward expectation outcome. So, just to remind people, dopamine reward prediction error. If you, you know, the dopamine system loves novelty, especially positive novelty, right? You don't think you're going to have a great meal someplace that turns out to be spectacular versus you're really expecting a place to be great. Your friend says it's terrific and then it's okay. And you get dopamine um codes for a lot of the expectation reward relationship. What you're telling us is that in most scenarios, it's more interesting than that. there's an updating of expectation before the final answer comes in and dopamine is coding for that. I'd like to um take this word foraging and apply it to a real world scenario in humans and then maybe we can uh use a combination of what's known and you'll also tell us where uh it might be conjecture to kind of paint this picture uh in an intuitive way for people. I have a friend um and she's on the dating market now. She will occasionally call me and ask me, you know, like, "How do I decode this text message or this interaction?" I try and offer my support, uh, where I can. Um, but the conversations often go something like this. Met so- and so. Uh, they seem really great. They seem really busy and they set a plan for like a month from now. Is that weird? You're like, "All right. Well, you know," and I give my my interpretation. I say, "Well, you know, he's nice. They've set a concrete plan. You know, this and that. Like person's busy, you know, this and that." Um, I also hear the, "Hey, you know, met someone, they're really, really terrific." And I say, "Hey, listen. The last time you said this, like two weeks later, it was how do I get out of seeing this person again?" So, like, go slow. Like, collect data slowly. And I'm not going to say I'm always right, but almost inevitably it's three days later or 3 weeks later it's like, "Oh my goodness, how do I get out of this thing?" Right? So, in some sense, it's what you're saying, right? There's a foraging for a healthy thing in life, a mate. This has happened since the beginning of time, although not with apps. Um there's updating of expectation based on experience and communication. And I think this is a really beautiful example of foraging in the context of updating expectations because and one could argue what is the final reward. Is it marriage? Is it whatever? Okay, that's that's subjective. But I think we all can intuitively understand this example um either by experience or by observation. So for someone, this person who gets excited about someone they just met, right? Then meets them and is increasingly excited, but it's unclear where it's going to go, then finds out as life goes that, oh, they're not perfect. There's this thing. Can I live with that? So there the I think of this as like a sawtooth of dopamine going through their system. Is that statement accurate that dopamine and other neurom modulators are encoding the sort of expectation of success or lack of success without actually knowing what the final end point is? Exactly that and that's the insight of Sutton and Barto and when I first heard about this I I learned about it from Peter Diane when I was a posttock and we both arrived at the Sulk Institute together something about it captured me because all of a sudden it's not this um okay you understand expectation and outcome I mean businesses understand that yeah you're disappointed you expected to have a quarterly return of X and you had Why? That's less. You expected it to be low. It was more. That's But that's really rare. I studied hard. I wanted an A. I got an A minus. Yeah. But the reality is embedded in this little simple continuous learning update rule. Um uh it's called temporal difference reinforcement learning. Um is the fact that in the world these expectations are going through their own trajectory. All right. And that's what dopamine is coding for. Any learning rule should code for the surprising outcome. You you you have an expectation for an outcome and either high or low of that. Every learning rule should do that. And the psychologist had that kind of figured out 40 years ago, 50 years ago. But it doesn't quite work because it won't account for the way animals learn. It won't let you chain events. So for example, if I show a light and go to and train on a reward with an outcome and I use that expectation outcome learning rule, it won't chain back to something that predicts a light. Suppose a sound predicts a light and we know the light predicted the outcome. Now I ask the question, well, what happens to the sound? Well, we know people learn. They'll they'll associate the sound with the outcome. It's Pavlovian. Yeah. But those learning rules won't do that. They learn the wrong thing. They just do. It's just not well appreciated. Now, back when we were trying to associate that learning rule with dopamine, there was we were mainly working on it in a in a kind of theoretical way, like if you had a signal, what would it need to look like? Where might you find this in biology? I remember my our adviser, Terry Sonowski, who's been on your show, I think he said something like, "There are these diffuse ascending systems. They deliver these transmitters. you guys go work on that. Sounds like his episode was spectacularly received. Oh, great. Well, I mean, and he was it was the most open, inviting environment, but of course, all the problems given out were impossible to solve. And I I remember just thinking, what? But um the first um inroad was realizing that it matched uh what Sutton had written down not so many years before. Sutton got his PhD I think in ' 84. I think he published the paper in ' 88. Um I was we were doing this in 1990 and we ran into a guy's data on dopamine signaling bull from Schultz. We didn't know him. We ran and we could explain every figure in every paper he published and we just thought, okay, that's not an accident. Okay, fast forward. We're in generation three now. We're going to come all the way forward. um people doing very fancy, very detailed experiments in rodents where you can control where you um where dopamine neurons are going to fire, when they're going to fire. You can control reward, okay? You can just control a lot of things. And so, uh it's clearly more than that. It's that and some other stuff, but that's central core. I I I don't see any good reason to throw away that little explanation there. Back in 1990, the complaint was, "Well, that's really cool. It matches these traces in a arcane um journal of physiology paper. What good is that? Reinforcement learning like that can't learn anything. The problem with that was at the time it was right. Like there were no systems that had done anything amazing. Now they've done everything and it's it's insane how good it was. You're talking about the AI. That algorithm that I just described with my hands waving is the same thing that David Silver and the Deep Mind Guys did when they made the world champion GoPlaying program and it beat the world champion and that particular game had uh expert advice built into it. Okay. And they removed all that and then they trained it from scratch. It's called Alph Go Zero. And then that game was was amazing. this item. It's never been beaten. It basically beats the history of Go. And so that as an example, it's such an amazing that's a breakthrough. Anybody that knows that side now, that's the that's the AI side. That's the algorithm. But that same algorithm is installed in your head. It's installed in the head of a song bird. The interesting thing that's going on now is this kind of convergence, right? They're these they're these little gremlins in in your brain stem that run that algorithm. Okay, they've now been externalized and put into a computer program that now does things that supersede us. It's a little interesting convergence. It's the only thing I know of that's sort of crawled out of your mind into a program and now the program is doing things that we couldn't imagine before. And it matches the biology. I mean, you can see this in creatures as old as honeybees and drosopha and whatnot. So, okay. So, a couple of things. Uh, one comment and a couple questions. Uh, first comment, um, I'm just going to say, uh, so that you don't feel you have to. Um, everyone should know that when Reed says dopamine is responsible for X, Y, and Z, there are many other chemicals in the brain likely involved as well. Other chemicals. And dopamine has multiple functions. Yeah. Yeah. I I just like anything in biology. Yeah. We should just embed that's up on the chalkboard now so that if you want to mention it again, you can, but don't feel obligated to. People, we're talking about dopamine through a narrow cone here, but certainly serotonin, acetylcholine, norepinephrine, peptides we haven't even discovered or understand yet are are contributing. Dopamine is clearly a major player. I want to step back to a um a human example, a non-AII example with the understanding of what you just said, which is that the algorithms that AI is running are based on the same algorithms that neurons in our brain stem are using to deploy dopamine, which I I don't know of an example like that in the world. Do you? I don't. I mean where we've discovered the nature of an algorithm once we externalize it we write in code and then it takes a few very special groups to all of a sudden have giant breakthroughs using that same algorithm and those breakthroughs are going to end up pumping information back into our head and so we live in an it's an interesting recursion there um I don't know what will come about yeah the fact that we took biological learning rules and gave them to a computer essentially um and the computer then can beat our own use of the biological learning rules um is pretty spectacular and I think it's a little scary but I want to shove that for for it is a little scary later in the discussion I I want to return to um the dating example you're going to hang this dating example around my neck I think that um and and we can partner it with another example which dating example is good you you you go along in an interaction with somebody you pick up new knowledge about them on Thursday you don't necessarily even see them. It changes your expectations of them. You pick up some new knowledge on Saturday. You run into a co-orker of theirs. They say, "Oh, I hear you're seeing so and so. Did you know blah blah blah blah blah?" You get a new changes changes your view. So, what I want to know is what is dopamine doing in the context of the constantly updated expectations? We know that dopamine is involved in motivation. Are the changes in expectation modifying motivation to either move forward um become more pessimistic, more optimistic or stay neutral? That's a great question. So, uh expectations change. Those changes in expectation encoded by positive and negative fluctuations in dopamine. Where does motivation come in? Uh Todd Braver and John Cohen had an idea about that and I think Matt Botven Venick too and that is those prediction errors are perfect signals for deciding how motivated you should be. How much should you want a thing by measuring uh AC across those kinds of signals. And if you were doing an experiment, you were trying to look at dopamine. Depending on the time scale you looked at, you might see little changes in it that correlated with fluctuating expectations. And you might see something as a kind of an envelope, a slower changing thing, which is the kind of experiment you might do in a experimental psychology setup. And that would look like it correlated with motivation with all these little wandering things going on underneath. That's the sense in which it could do both functions. We are told that dopamine is what we're seeking as we go through a social media environment or we go through a dating environment or we go through a financial environment that we're investing or investing time in. But as you mentioned, dopamine is not just that, you know, at the finish line. We've known this for a while now. It's part of the neural circuitry uh algorithm that's driving us forward or causing us to pause. But is it fair to say that any system, whether whether it's a social media platform or it's um another form of business, whether they consciously realize it or not, and they probably do, it's built on trying to constantly update our expectations so that we keep playing the game, so that we stay in the forging mode. Because if you think about it, it's an infinite scroll. There is no final outcome. If there was a final outcome, you wouldn't keep living. You want that system to keep tracking and once it gets to one place, you want it to have another place to which it could go. Otherwise, you wouldn't live. Probably one insight into why it's in every mobile creature's brain on the planet. So if any goal that you achieved, whatever it is, taking a drug, eating a food, u getting a a partner or whatnot, um if that was enough for you, right, then probably be a hard, you know, that's not the way your nervous system works. Your nervous system keeps pushing you forward. That's what you're working for. You're working for this push forward drive. the mapping that onto dopamine hits um is um it's not wrong, it's just blunt. It's just a blunt way to say it. It's not wrong, but it is blunt. It's a blunt way to say it. You you you move around with expectations before you get any sort of big unexpected hit. This is why I don't like the phrase or the words dopamine hits because it implies it's like a reward that gets trickled into you. But it is true you get a hit. Mhm. It is true that there's this unexpected reward that you that your expectations, your series of expectations did not anticipate and that augments that is the learning rule. That's that's what we think uh the the dopamine fluctuations are encoding. And so it does both jobs. It it lets you update and learn and it codes for the kind of motivation you should have. And when you're surprised, those are extra hits. So it it's not wrong to say that. It's just incomplete. I'm going to ask you to speculate a little bit here, but speculate within the context of what you know about dopamine, which is a lot. Um, let's take any of the different examples that I threw out on the table for us, and we artificially ramp up levels of dopamine with, let's not say, a drug of of abuse like methamphetamine or something, but you know, we throw a little bit of a dopamineergic stimulant into the picture. Does that just raise the the kind of the height of the saw tooth? Uh does it change any of this? For instance, if um uh this person who goes out on a date on the second or third date, they go to something that like maybe a show that's spectacularly good. Okay. How does that change the dynamics when you know it's now it's now there's an association with this person, an event, but let's say that they're flooded with dopamine. Let's take a drug out of the picture. the the the experience generated more dopamine. Does it shape their expectation and motivation around that person? If you raise expectations and these code these are coded by changes in dopamine, then in fact that's that's sort of a tonic question. That's sort of a tonic phase. You explain tonic. Most people are think tonic. Well, so slower changing. Okay. So I see a show. It makes me very excited. Uh I have the well fills up with a little more water. Okay. And it's sitting here. So now the little hits on are on top of that. Or I see something that depletes it. I take a drug and some drugs deplete dopamine. Or they went to a play and it sucked. Yeah. It's disappointing or it's sad. He's got bad taste. Yeah. Yeah. It just runs in your mind. So So that can lower the levels and that changes the way in which um the fluctuations have an impact on learning. Okay. Parkinson's disease is a condition where by the time you show up with symptoms in the doctor's office, you've lost 70 to 75% of your dopamine neurons in your brain stem. Those are the only source of dopamine in your brain except for a tiny pathway in your hypothalamus and pituitary. Well, there's sorry retinal biologist in me. They're doing things totally unrelated to any of this. They're controlling adapt adaptation of light levels. Yeah, light level adaptations and um certainly in goldfish. Uh um yeah, those are actually very interesting. I won't talk I won't talk about them. So you got the the dopamineergic brain stem neurons that degenerate in uh by the time you're feeling so stiff uh starting to have tremors all the parts of the flat facy flat affect and um and somebody's gets you to a doctor you're you're in the 70 to 75% loss. Okay. So what does that mean? Now all of a sudden these and and dopamine neurons in your brain stem or maybe 80,000 neurons per side, 160,000 neurons, that's like nothing. They send dopamine delivering wires, biological wires throughout your entire brain and down your spinal cord making hundreds of millions of connections. But now you've shrunk those down. And so the one thing that happens is it's very noisy. there's not so many neurons to to code for it. There's no smooth changes in it and the no the noise floor relative to what you could generate as a signal gets really really high. Well, one of the things that we think dopamine is involved in in terms of information processing is valuing the world computing if you will the value of taking this action or that action, the value of grabbing this and putting it in my mouth and drinking water etc. Okay? And the Parkinson state is sort of like a flat value function. You can't really see differential value in things. As you look around the world, you expect the system to fluctuate for you to tell you if I were to do this stuff or if I were to do that stuff, if I were to look at that, etc. It gives you a fluctuation, but you can't read it. The downstream, it's too noisy. It's too noisy. You can't read it. The downstream system just has to act as it did before. It says, "Oh, everything's of equal value. Just stay stay put." So I've always thought about Parkinson's as an active freezing disease that the nervous system is doing exactly what it would do if because it takes energy to transition from where you are to doing the next thing. Why do that if it's there's nothing more valuable there. This comes back to the idea of it pushing you through the world. It doesn't habituate because it has to keep your behavior going or else you're going to die. I don't think it's a coincidence. In fact, I know it's not. That dopamine is involved in learning, motivation, feelings, and movement among a few other more minor roles. Uh, everything about physical movement is intuitive to us. You move forward, you move back, you move side to side, you stay put. Okay? like movement, the idea that that levels of dopamine in in a moment and what you're referring to as the tonic kind of um baseline, what I call baseline levels of dopamine as opposed to spikes on top of that um predict whether or not you'll move forward, how much resistance there is to moving forward, these kinds of things. But I think for a lot of people it might be useful to think about dopamine in the context of thought movement, right? And motivation is is sort of a a a version of forward movement. You know, in if I think about am I motivated to do something? I don't I no longer like the word motivated. I decided I like the word a sense of urgency. You could have a low level of urgency, moderate or high level of urgency. Urgency I define as um sort of a persistent resilient motivation, right? And the reason I prefer urgency to motivation is that a sense of urgency is is more intuitive I think to most people. we kind of know when we feel we have to do something, we really want to do it or like it's we don't really want to do it or we're procrastinating. Whereas motivation is this just kind of like catchall term for how motivated are you? They think intrinsic motivation, extrinsic motivation. So when I think about a sense of urgency, I think about a sense of a need and readiness to move the body and or move thoughts in a particular direction. Do we think that dopamine is involved in moving thoughts and decision-m in a particular direction? We exactly think that. Okay. Thank you. I wasn't asking you to validate my my non- theory theory. I just I want I think that dopamine is thrown around so much nowadays that we don't even really understand what motivation is, let alone how dopamine would be playing this this it's very clear dopamine and the other neurom modulators are involved in um stabilizing and sustaining brain states. Okay, that's why they're thought to be involved in seizures, right? One thing you have to do with the brain state is kind of hold on to it a bit. It's got to have a dwell time, right? Let's call that a thought. Boom. Okay. Uh and then it it goes forward or changes and then it may come back to that. Okay? So thinking and sequencing through what you would call thoughts is something that these systems are clearly intimately related to. And there are a lot of great groups now that are exploring this in in mice models and theoretical models as well. Um so I think you tie the words together pretty well. Um in an animal that has to keep moving to stay alive and that's all animals. Um it has to know how valuable is it? How motivated should I be? How much should I want a thing? Right? um the calculations that we think the algorithms are affecting in your in your brain are exactly those. And so we can have these conversations at the level of these psychology words which are interesting and pertinent to the way looking at an animal behave. But now we're starting to pull it apart at the level of what is this computing? How fast is it computing it? How did it update it? And now we can build artificial systems based on that. Um and I think um there was a paper in 2004 by David Reddish talking about um addiction as a computational disease gone arai where you keep feeding system um a level of dopamine by putting a drug in that c blocks its re-uptake that it can't anticipate, right? And so it keeps chasing that and it never gets there. when people have ADHD, even low what low-level ADHD um or they take a drug that um increases dopamine, do you think that it makes more things in the world sticky, meaning uh mentally sticky, like we we naturally just will latch on to more things when our levels of dopamine are elevated. We'll forage more randomly or do we forage more narrowly? Because the whole notion of ADHD is that they they the whole like oh squirrel like that's the kind of generic example is that someone with ADHD um the theory is that their dopamineergic systems are disregulated. These drugs, almost all of them, right, whether or not it's rolin or aderall or these other drugs, they raise levels of dopamine and norepinephrine. Oh, yes. And somehow put people into a more narrow trench of of focus or give them a little bit more selectivity in terms of what um what paths they decide to forage. Yeah. I suspect, if you made me guess, that it's stabilizing brain states and thought sequences in a way that's um narrow and it doesn't divert. Does that surprise you that increasing dopamine would do that? No. Bees do this. Okay. So, when you're a forager bee, uh you come back and you do a little dance in the hive and it tells the hive uh other foragers where to go find the nectar source. Okay. And it's a it's a whole language. People have worked that out. It tells you fly this far with the sun here and there's a polarization. It's an amazing phenomenon. Yeah. Yeah. that the bees go back and they literally they do this dance the waggle and they feel the the the waggle dance on the bee and by feeling it they know where to go wild well it's a language you can decode I mean it's been decoded it's very to some degree when you look at bees I know this because I've been working with a bee guy Brian Smith at Arizona State University for the last few years I've known him my whole career but I've now has some methodology that lets him make measurements of dopamine and serotonin and norepinephrine in bees while they do odor learning. And um he has bees on an axis. Okay, way over here are the ADD bees, let's call them. And way over here are the concentration bees. Okay, and it relates to a chemical that's related to dopamine called octopamine, but it's a ratio of octopamine to it's called tyramine. That's like dopamine and serotonin if you were talking about primates. The ADDBs, they they feel the waggle dance and they start, you know, they start running for the nectar and then they get distracted. You know, they're the four-year-old. A lot of adults like that nowadays, too. They and they can't. Of course, what they do by being distracted is they explore more. Okay. And then the ones on the far end over here, um, they fly right to the nectar source. Okay? So, you need both. you need. That's called exploitation. This one's exploiting where the nectar source is. It's going to get it. It's going to bring it back to the hive. And the the sort of add guys are the um explorers. They're looking for new information, new nectar sources, etc. Well, your mind kind of, as blunt as that is, your your mind plays this dichotomy in the same individual. You think that we have this ADHD like mode and a more focused mode. you've got multiple bees inside your head. One of them is making you into the explorer and and that's really really valuable sometimes. Okay. And companies they they keep these people around. These are the uh lateral thinkers and you know you just have to you know feed them enough. Um and then you have the people that can really follow instructions and follow the best course of action and whatnot. And you need all that. Need all that. And this distribution of abilities is built into all of us, but it's different across us. You know, if I was looking at an oak leaf and I told you, what about this little wiggle? It's it's the wiggle in our software design for motivation and learning. Um, it's very effective to sometimes be the explorer and other times you have to be able to follow the chain of this is going to lead you to the thing that you want. Stay on course. If you're a regular listener of the Huberman Lab podcast, you've no doubt heard me talk about the vitamin mineral probiotic drink AG1. And if you've been on the fence about it, now is an awesome time to give it a try. For the next few weeks, AG1 is giving away a full supplement package with your first subscription to AG1. They're giving away a free bottle of vitamin D3 K2, a bottle of omega-3 fish oil capsules, and a sample pack of the new sleep formula, AGZ, which by the way is now the only sleep supplement I take. It's fantastic. My sleep on AGZ is out of this world good. AGZ is a drink, so it eliminates the need to take a lot of pills. It tastes great and like I said, it has me sleeping incredibly well, waking up more refreshed than ever. I absolutely love it. Again, this is a limited time offer, so make sure to go to drink ag.com/huberman to get started today. What you're describing is a sort of ADHD like mode inside of all of us as well as a highly focused mode inside all of us. You're also I I think I hear you correctly in um thinking that you're also describing the fact that some people are very strongly ADHD mode and other people are very strongly focused. Um they're very linear uh taskbased task. They can really uh form a task, hold it in mind, a task stays there. You know, lots of lots of athletes are that way. They set a goal um and they set multiple scales of goals. They set some goal, you know, this is where I want to be in two years. Okay, to get there, I'm going to have to do, you know, I'm going have to crawl through, you know, hell to get there in two years and I have to do these things and I'm going to wake up again tomorrow morning and again and again and again and these goals have to be reconstituted and pursued. Um, if you, you know, wanted to go play in the NBA and then all of a sudden six months into that you decided you want to go do ice hockey, well that's a problem. That's a person who can't can't focus. We all know these people. One question I have and we can only speculate here is you know there's a lot of uh ideas now that social media but when I say social media I don't want to knock on I teach and learn on social media. I what I mainly thinking about is um short very short form video. There's this idea out there that it's quote unquote giving everybody ADHD. Now, I don't actually think that's true, but I could imagine that if we have this continuum of honeybee like modes in our uh in our brains that if we repeatedly engage in a kind of rapid turnover of stimula like you get when you scroll a Tik Tok or a you know YouTube shorts or something like that, I mean there's a very frequent updating of lots of different contexts um and information that those circuits might get stronger And that the circuits that uh allow you to move from node to node and route to a goal, updating as necessary, understanding and integrating expectations and rewards and failures and all the above, right? The athlete example, the academic example, any life, navigating relation, all the the stuff that we think of as building a solid life, right? You could imagine that some of that rapid updating and foraging could undermine the circuitry. No, you build your ADHD muscle. Is there any evidence maybe from related or or or other experiments entirely that show that if you give people a task where they have to update very quickly that you shift the the sort of state of the brain toward seeking that more and and doing that more easily than you do kind of like long long haul uh distant reward type stuff. I don't know the answer to that in people, but I do know about training artificial systems to do it. And you have to be very careful to control the mix so that it doesn't overtrain on some on one of these two possibilities. If we're going to divide these two possibilities, chase a goal, chase everything that flies along, right? And you don't want to do either one of those things. You have to balance that. And sometimes you have to impose constraints to make that happen in an artificial network. It's a more complicated problem in people. I mean I can imagine I know lots of settings for being ADD is an absolute requirement. Can you give me a few examples? Combat combat rapid decision-making kind of the fighter pilot u situational knowledge. Now what do they do to prepare for that? By the way, my dad was a captain in the Navy and I have lots of combat examples in my head. Um well they they practice they practice they practice being surprised. They practice being hungry and you know they they put themselves under stress and all so that when that happens they don't have to run through every possibility and you're they're very effective but that requires training that requires an enormous amount of mental training. It's all it's it's all about the mental game. Yeah, it's a good example. Uh we've had a couple of experts in ADHD on here and um all of them have agreed that um children and adults with ADHD, mild or severe, can focus very intensely on things they really enjoy and are interested in. It's not a lack of ability to focus. It's that the um there's a lot of choppy terrain to get into that narrow mode of focus unless it's something they love. You give a kid with ADHD a video game they love, they'll drop right in as if it was, you know, the most focused you've ever seen them. Anytime you have to do rapid fire decision-m, I think you would want somebody who was able to at least train up to that level there. Do you worry about the overexposure to um you know frequent media? Yeah, these media. I have a lot of kids and so like every parent, my main nemesis is screen time. Okay, I'm trying to figure out how to monitor it, measure it, restrict it, and you know, and basically my kids are smarter than me and they're they're more nimble and they they move faster than I I mean, so it's a battle I'm losing. Um, so I've decided that the only way I can combat it is to lose it, but lose it a little more effectively toward my side. So, um, but I have to admit when I see YouTube shorts, these little, you know, like, oh, look at this person. He built a house out of Jell-O and it's falling over now. Okay, look at this other person. There's a parakeet poke poke. I mean, it it's mindnumbing to me, right? Well, there isn't a lot of long-term learning. I, you know, one of the things that I define learning by as uh useful learning is did I reflect on it again at a point later in time? You know, the other day I was on social media and I actually saw a clip. It was on a friend of mine who has a podcast um Steven Bartlett and he was interviewing a guest and um this speak gets right to the heart of this conversation. You know, a lot of stuff flies by a lot of wisdom type advice, you know, health advice, all the you know, it's constant barrage, but this one stuck with me. It's interesting. Um he asked the guy, "What's the meaning of life?" People ask this on podcasts. I won't ask you that today. That's that's a Lex Freedman question. When you go on Lex's podcast, he you can answer it to him, but I won't ask you that. But Stephen asked this guy, I forget who it was, so forgive me. You know, what do you think the point of life is? And the guy said, "It's to learn to enjoy the passage of time." And I thought, "That's pretty awesome. I would add to it and also engage in behaviors that buy you more time, you know, is it make sure you don't undermine your the time piece of it." But, you know, it was something that flew by on social media, but stuck with me. Mhm. It is exceedingly rare that a short clip provides entertainment or information that really stays with me that I reflect on it later. Whereas when I read a book, it's exceedingly rare that I don't have five or 10 things underlined per chapter that I go back to later. It takes a while to read a book. That's the thing. You it takes a deliberative set of intentional actions to read a book. That's the difference in the modality. So, one thing that uh this speaks to then is I've wondered whether activities that require effort that may or may not include reward but that include effort and that are a little bit slower and effort and slower tend to go hand in hand um not always. Uh whether or not that is part of the mechanism that strengthens a circuit. Does effort strengthen an algorithm? uh in other words um if I get on social media it's very easy to scroll scroll scroll scroll scroll short form video content doesn't take any effort um so and in fact there's no learning involved all you have to do is move your thumb but there's really no learning involved whereas if I have to do something if I have to puzzle into do a puzzle to get in or if I have to solve something or think about something or grapple with something that is where the learning occurs what's the relationship between if that we know between effort and dopamine. There is a good bit of work now where people look at the amount of effort an animal has to do to accomplish a task. Let me just go back to something you just said which was interesting. When you have to do effort um it's easier to learn something because it slows you down. I don't know whether effort is itself the cause or whether the fact that effort is slow and so it slows it down. Maybe we could design an experiment to maybe slowing it down. It immediately gave me this idea. Um, so that's true in simple experiments with rodents, but you know, rodents can't read very well. I've never seen a rodent that I admired that could manage a cell phone very well. And you know, even the rodents that can read are kind of flat effectively and all. I mean, rodent is a terrible model for this really. I I I wouldn't even do the experiment in rodent. to do the experiment in a human. Yeah. Where you can with a few words set a human in a certain state and you know go or you can make them hungry or you can you know you can put a human into a mental state by just asking them to think about X Y and Z and have various controls to account for that. I have to admit that when I look at the generation we're concerned about I've just read this book the anxious generation. Oh yeah. Jonathan was on this podcast and I was on a MacArthur network um neuroscience and law with him for a while and he he's just a extremely clearheaded person really um always made me think about things on the other hand I don't know um other than the comparison to others and the speed at which social media lets you do that and I have you know I have girls mainly four girls and one boy Um, I don't know what it's doing to him exactly. We We all Okay. I I don't think anybody does. I think we all suspect there's features of it that aren't good. And yet, it's like we're trying to hold back the tsunami. I mean, it's just the water's going past us. And so, I think the only way to uh deal with it is kind of fly by wire. um you know when a little fire starts over here and somebody says oh this really causes a depression in mood and it's these features of it then we can go react to that and all but it's very hard to know what it's going to do globally it's it's it's it's evolving with its own it feels like it's independent of anything we do and so I I I I think it's going to have to be a re sort of a get in front of it reaction you can't for example my kid just got a cell phone. She's 13. She was the last, according to her, and she's the reporter here. She's the last seventh grader in her school to get a cell phone. And but the the raw fact was she I'm being left out of all the discussions and whatnot. And the answer was that that is true. She is being left out. Their their mode of choice is Snapchat now. Um well, there's a lot of downside to Snapchat. And um so now I'm the I my nervous system and my physiology is now hooked to her blizzard of time requests on my phone. It did, you know, I turned it off before I came in here. Um on the plane flying over the country, I'm denying things and giving 15 minutes and whatnot. So um Jonathan has real prescriptions for how to fix that. He has good suggestions for how to fix that. But the collective action thing is, you know, collective actions are hard because, you know, they're collections of humans and you just can't get people to all do something at once. There's always a defector. Well, I think as long as we're also training the other more slow, effortful type integration of knowledge. Um, I mean, it'd be wonderful if social media had settings where I could click entertainment. I would just get entertainment stuff and then I knew how long I was doing that versus educate me because I do learn a lot from social media and I certainly try and learn on social media. Um, and this what may sound like kind of a trivial statement the other day and learn to enjoy the passage of time was what sat with me in some way that felt important to me at that moment and um I've been reflecting on it through a couple of different lenses. We're obviously not going to solve this problem. I am curious about speed versus effort when foraging. Let's take it back to the dating example. This person's gonna kill me for I'm not going to reveal who she is, but you know, I said, listen, I've noticed this pattern over time. You discount people early or you get very excited and then it always kind of kind of ends up in the same place where you're like, uh, why did I do that? And I was like, well, let's, you know, so maybe run a different algorithm, maybe start to collect data a little bit more slowly or maybe, you know, see them more frequently for like two weeks and then make a decision so it's not you didn't waste so much time. Still more frequently means more time, but not overtime, you know. So, um, we can change our our mode of foraging. I I personally put social media on an old phone and it goes in a supermax prison uh lockbox that you can't code out of for 22 hours a day. You do that to yourself. I do. And not like the person that can't avoid eating chocolate. K, you lock the chocolate. It wasn't that. I just I'd read this paper that was published recently that said that if your phone is upside down on a table or in your bag in the same room, it lowers cognitive performance. Even if you're not aware of the phone, then you it's it's pulling resources. It's pulling resources to it's pulling resources. if it's in another room, it seems that your cognitive performance returns to its previously higher levels. So, I thought that's pretty good. So, I started keeping my phone in the other room. Um, and I thought, how how much further can I take this? So, I think that the physical distance from things that's non-negotiable feels really good to somebody like me. Out of sight, out of mind, maybe. Although, I want to bring this back to dopamine. uh you know can the dopamine system learn to uh to get motivation states and pleasure from resisting things. I think of a pathologic version of this might be we did an episode on anorexia where food is rewarding for most people but for people who have true anorexia um the reward system seems to enter a state where uh resisting food becomes the reward. Control feels good. Yeah, control feels good and but there's po anorexia obviously the most dangerous and deadly psychiatric illness of all the psychiatric illnesses but but resisting your phone um to get other work done and to be more present for people in my life including myself but you know that seems like a good thing. So can the dopamine system um encode reward for resisting behaviors as much as it can for indulging behaviors? Yes. I mean, I think anorexia is a good example of it. It feels good to resist and they do it pathologically. It's such a dangerous disorder. Um, but in a healthy sense, like I'll reveal now that you were a a fairly accomplished dathlete. Um, so that meant getting to practice, doing things, but did you ever feel like I'm going to bed early when everybody else is staying up late? I'm getting stronger. Oh, I relished the whole I'm running this tennis court hill while all those other soft guys are, you know, asleep and I'm throwing up on top of the hill. Yeah, that was a that was a thing. And it meant when you got in a tough spot, um I was a wrestler all through high school. Yeah, they're sickos. Yeah, they're sickos. Yeah. And but you're never in better shape than when you're active wrestler. um you have to put up with things that are really demanding on you like you like having your air cut off. So the main thing you do when your air is cut off is don't panic. Well, that's not you you know you're not pre-built to not panic. So you have to learn how to do that. That was the most important thing I did in wrestling. Just learn to stay calm, think about where your weight was and all that. Um it's the same thing for people that study a lot. I think people that study a lot want to be better than the people that don't study a lot. I mean, they want the idea of achieving a goal. Um, that's hard for other people to do. And the most healthy version of that is without any regard to what anybody else is doing. The person who just this is the life I live and these are my standards and I'm quiet with them and I'm going to go do this thing and it doesn't matter what anybody else thinks. And you hope that for your children, you hope they get to be a person like that. Um, anyway, I can tell you my kids school, just to circle back, their collective action is to completely disallow phones during the school day is junior high school. They go to a school that's K through 12. Mhm. Um you have put it up when you get there and I think 3:30 is when you can activate to call for a ride or whatever. Um and it's off. It's off. It's a f the Well, I like the head of school. Uh but her that's the best decision she's ever made. I mean that that's a great decision. Um and now they're wrestling with what do we do with AI in the school? How are we going to let these kids interface with these systems that are smarter than us? More interesting, no less. I want to talk about AI. Um but before we go there um I think you've painted a really nice picture of dopamine and the various things it does and even just this early statement that you made that dopamine is is fluctuating according to our constant updating not just expectation reward but expectation expectation expectation expectation maybe the reward never comes maybe it does let's talk about serotonin because not in every case but at least in some cases my understanding is that serotonin is fluctuating in the opposite direction to dopamine at least in animal studies it see these are some interesting in human studies too great so educate us about serotonin in this context because I know it's a huge topic right a habit that people that work on neurom modulators I'll name a few dopamine serotonin norepinephrine acetylcholine histamine um probably on the order of let's say 15 to 20 let's say and then there are a lot of peptides and all but the big three dopamine serotonin norepinephrine um learning and motivation uh active inhibition um attention that's what people would say ep norepinephrine and epinephrine or controlling attentional states serotonin tells you to get ready to wait like you put an animal uh you put a piece of cheese over an area of a table and there's an electrified grid on the table. The animal knows it's electrified. He really they see the cheese, they want the some rodent. Uh they see the cheese, they want the cheese, but the light is on that means that the grit is active and they're not super hungry, so they wait, but you know, there's a part of their nervous system that's making that hard. Active waiting. um which also suggests another set of things for serotonin that it's uh learning about negative things. Dopamine is learning about positive things or the absence of negative things or the Okay, so there's there's ambiguity in there because the experiments aren't all that clear yet. There's an enormous amount of work going on in humans. We are the only group who records sub-second levels of dopamine and serotonin in conscious human beings while they do things. Reward motivated tasks, social interactions with other people, uh various kinds of visual perceptual tasks, looking at emotional u pictures, positive, negative, and neutral and whatnot. The theme that emerges from that is dopamine and serotonin are opponent to one another. When dopamine goes up, serotonin goes down. When serotonin goes up, dopamine goes down. We could talk about those events as being for positive events or anticipation of positive events. Dopamine goes up and serotonin goes down and opponent see that. um at your own institution, Rob Malinka has a a set of beautiful results in rodents where the learning that they see in the animal requires that kind of opponency and I mean it's a definitive experiment in the rodent. Um, it's harder to do these things in humans because you can do simple things in humans. That's fine. But humans can sit and have an idea and it can generate these kinds of signals and they can run through the ideas. And so that that's a hard thing to both get our hands around and to do in a controlled setting. And so that's why it's been ambiguous. But the first time we were able to measure dopamine and serotonin concurrently, they look opponent and they look opponent all over the place. They're old ideas uh from the 60s and 70s about opponent systems in this sort of a effective processing space. Dopamine has now inherited the positive part of that and serotonin the negative part of that. Opponent as you know is a a theme in the nervous system. In the retina you have color opponency, you have light and dark opponency. These kinds of information channels go all the way through to the visual cortex. One other thing that's interesting is that when you put SSRIs on people um you prevent ser selective serotonin reuptake inhibitors KAC fluoxitine luxro um it blocks the re-uptake of serotonin in the serotonin terminals over a few weeks period you have a clinical effect and you know for some people it's a life changer It's very heterogeneous. Um, but it pushes serotonin into the dopamine terminals, too. This is less well understood, but you know, if you were a system and you thought that the positive juice was dopamine and the negative juice was serotonin and you put the negative juice in the positive terminals, then the cells that control the release of that are going to chatter for positive things. You might start negatively conditioning on things that you should actually pursue and learn about. SSRIs have helped a great number of people. There have also been some devastatingly tragic circumstances where SSRIs have the theory is that they've accelerated uh suicidality. They've accelerated ahidonia. They they've created a lot of problems. If we were to just take a step back in terms of serotonin as learning about negative things, if you could just summarize these results for me AC animals and and what the expectation would be in humans. So, let's say that somebody or an animal is learning a a task where they get shocked. If one were to artificially increase serotonin, does that make somebody or an animal more or less likely to code something as negative? Well, the idea would be it makes you negative because you have less serotonin in the serotonin terminals. And so if they're communicating this information about more serotonin in the serotonin terminals. Gotcha. So if somebody takes an SSRI, serotonin is increased and they have a tough interaction at work. Uh the idea is that they would encode that cognitively as less bad because there's an abundance of serotonin or worse than it would be had they not been on this drug. When you increase serotonin in your brain because you won't let it be vacuumed out by the normal mechanisms that clear it from your brain, then it has the opportunity to be there longer and it has the opportunity to go into the dopamine terminals. This is something we know. The the mechanisms that suck dopamine out of the spaces of your brain um will also bind to serotonin and suck it out. Not quite as well because it's tuned. It's called a dopamine transporter. Um, and so depending on what the downstream parts of your brain think, then in fact increasing serotonin could uh decrease the serotonin in the serotonin terminals by blocking the reuptake. I see. So that's why you said it earlier. I tried to correct you saying no, it's going to increase serotonin because you're blocking reuptake. You're saying no, it pushes serotonin into the dopamine terminals and this is why people might not get as much reward from a positive event. Correct. When serotonin is elevated pharmacologically, there was a killer paper 20 years ago on that where they showed they gave rodents um some common SSRI they waited this number of weeks and they went in there to say where is the serotonin. Okay. And what they showed was that the dopamine transporter pathway was the thing that was taking it into the dopamine terminals because that's where the dopamine transporters are. And so I don't know where that's gone since then, but that's a 20-year-old result. It's a very clear result. It was in a journal called Neuron. John Danny was the senior author. He's at Penn. Um was a remarkable paper. I don't know that people have followed up in humans. I actually think the only way to follow up in humans is to kind of do what we've been trying to do, which is develop methods of measuring these things in humans directly. Uh we've been able to do it in people that are having brain surgeries and they have an affliction. They're going to have a electrode put in their brain for various reasons and they let us piggyback on that. They consent obviously under strict ethical guidelines. Um but we can measure serotonin and dopamine when they do a rewarding task or they play a game that has a series of things that go on back and forth with another person. um which I like better in the sense that that's a more natural reward. Somebody does something to you and you do something back to them. Usually in our case they're economic games. This is encoded in money or the expectation of the money that's going to come and you can see strong opponency in dopamine and serotonin signaling in the amig deep structures in your brain. these experiments, if people positively anticipate um because things are quote unquote going well uh for them, uh you see dopamine going up and you see serotonin going down. And if they're losing at this game or they feel like the game isn't going well for them in some way, um there's more uncertainty perhaps. Serotonin goes up and dopamine goes down. Yes. Interesting. And then there's state changes in your brain that can be induced by, for example, making somebody hungry where we don't really know how to explain what we're seeing, but they still show opponency. What would you say uh being hungry does to the dynamics for let's just take them one at a time, dopamine, does dopamine still increase for positive events when people are hungry? No. No. Not in rodent in rodent model. I can talk about rodent models. We are actually in the middle of doing something like that now where people come in in the morning hungry. Uh in this case, these are people with epilepsy that have wires in their head. Um and we do an experiment on them when they're right before they're going to eat. And then we repeat the experiment after they've eaten. But in rodents it's very clear uh I guess at the level of the amydala if you make a rodent hungry then you can show that dopamine will encode um something like punishment prediction errors not reward prediction errors. In other words it does it's like it flips its role. It's like if you're in a how hungry do you have to be? I don't know how it feels to be a hungry rat but um imagine that it put it in an emergency state. Okay. So, it's not just a kind of like like I mean I don't do any formal intermittent fasting, but I usually eat my first meal somewhere around between 10:00 and noon. Uh, and at 9:00 a.m. I'm like mildly hungry. I could eat, but I'm by four. You would be hungry. I'd be really hungry. You'd be you'd feel it. You'd feel what we've all felt when we're hungry. And um this is a guy called Mark Anderman at Harvard. Oh, yeah. I know Mark. Yeah. So, he puts animals in starvation states and he shows that dopamine will encode aversive events, aversive errors. very clear result. So folks, I know this because he called me. I mean, we we we met. So when your kid boyfriend or girlfriend is hungry and you're going to a show or you're going someplace, you got to feed them if they want to uh if you want them to enjoy the time. I mean, that's sort of obvious on the one hand, but I don't think we really Oh, it's even better than that. There's an Israeli paper from I don't know about 10 years ago where they looked at judges and the judgments that were made if you hadn't eaten versus judgments that you made that you had eaten and you really want a judge that's had a good lunch. Very interesting. So general state of stress because hunger is a form of stress. uh drives the direction of the dopamine um to either reinforce positive things or reinforce negative. Yeah. Cuz think about it. If you get to a state where you're really starving, things have not been going well for a long time. You've been making really bad decisions. The creek dried up. The, you know, some forest fire came through and ruined your your foraging area or whatever. things are going really really bad, are you going to really sit around and wait for the the rewards? The main thing you want to do is stay alive. If you don't stay alive, it doesn't matter what rewards you chase. And so, in a sense, flipping dopamine's meaning is exactly what you'd want to do. You're in an emergency state, and you want to use this reinforcement system, this expectation system to stay alive. You want to pay attention mainly to those things. You want to pay attention to them. You want to be motivated by them. We want to be motivated and pay attention and avoid the negative things. But that's an emergency state. When I talk to people about how um reinforcement learning models say have an impact on how you should train an animal, uh typically in my case, it's in the laboratory setting, but you could use this other dogs for example. Training animals with really negative feedback is a really bad thing to do because what happens when you get really negative feedback. You're in a mall, somebody shot beside you. That's negative feedback. What happens? You have in the extreme case, you have PTSD. But what you do is you overgeneralize. That was so bad it's rational for your nervous system to think anything that looks like the mall, the the fear will start to come. It'll move out to the curb. It'll eress. This is the whole PTSD cycle. But that's rational. That's rational. That was a that was an absolutely unexpected cataclysmic event. You better and you don't know what could have caused it really as as far as events leading to it. So you overgeneralize and all. So you don't learn very well like that. So you know a teacher that instead of when you miss when you're trying to add fractions and you don't get a common denominator quite right. Um, when she takes a ruler and slaps you over the hand. They could still do that when I was in school. This is a generational shift. A good one. Uh, that's a really bad way to teach me to find a common denominator. Instead, you could just say, you know, nudge, nudge, nudge. Anytime someone says, I have a friend, it's like code on the internet for like it's actually you and that's like the I have a friend, you know, but so I have a friend. Um, people might be surprised to hear that I have friends. Perhaps not. I have a lot of friends and um he's a lawyer and prior to becoming a lawyer he studied torture. In what context? Yeah. He was going to be torture 101. No, he was going to become a psychiatrist and he did a rotation with former victims of of torture and then it took him down this rabbit hole of political, you know, political torture and the history of that. He's a real history buff. He's a very benevolent person, very very very kind. Uh but he told me something interesting that I I think tells me that some people figured out this um thing that if somebody is stressed enough it um contorts the dopamine reward contingency um so that dopamine no longer encodes positive things. It just tries to prevent things from getting worse is what we're basically saying here. He said that the way that people torture people to get information from them is actually pretty surprising, at least it was to me, which is they hurt them a little bit and then they tell them they're going to hurt them a lot and then they don't. Rather than hurting them a lot, somehow what they by hurting them a little bit and then telling them this is going to get much worse unless people give up more information is it's interesting. And I think it speaks exactly to this mechanism where the mechanism speaks. If you hurt a person a lot, that's cataclysmic. That's categorical. I'm going to thank you for not breaking my arms again on Tuesday, right? I mean, if you you you break limb and you do these cataclysmic things which leave them near death. There's nothing left. It's a bad way to train someone. So, I mean, what I'm what I'm trying to say is I understand that. And the odd thing is when you stress someone enough, it's remarkable what becomes re rewarding. You know, the incremental removal of threat um given that you've made good on a little promise could be a lot. I I mean I Oh, I I've seen that. That doesn't even have to be as extreme as torture, right? read uh doses in family read dos jeski and look at the family dynamics and go you know they're dialing knobs on you know degrees of punishment and and it's very effective let's take the inverse of this let's shine some light in the room so to speak what if dopamine gets too high and I'm not talking about methamphetamine which will really skyrocket dopamine um I would say when people are on uh very high levels of dopamineergic drugs like like methamphetamine or cocaine. Everything seems like a good idea to them and they become very self-obsessed. In fact, um there's a wonderful documentary about the Grateful Dead that I watched recently before Bob Weir died um which they someone was saying, you know, at some point in the mid80s uh it got a lot harder to to make great music. And someone said, "What happened?" And they said, "Cocaine." He said, "Why would cocaine do that?" and he said because it's a me drug. Dopamine and cocaine are synonymous with one another. But there are a lot of situations where people are overindulging themselves with food, overindulging themselves with um dopamineergic activities. Um what does that do to the reward? If you look at it on the average, it resets expectations where very few if any natural events can exceed them. I'd like to take a quick break and acknowledge one of our sponsors, Function. Last year, I became a Function member after searching for the most comprehensive approach to lab testing. 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Again, that's functionhealth.com/huberman to get early access to function. So, I rescued a dog once. Um, back I mean when I was a kid, I I kept lots of animals when I was a kid. I had um my father told me at the end, oh no, you had over 30 cats. Oh my god. They stayed outside. That was back when animals I just kind of 30 cats. I had a cat. The cat had a litter. There were seven in the litter. They all survived. Then uh a good for you, man. I wasn't really a budding scientist then, but I realized in retrospect that I really watched them. Okay. And understood the behavior. And there was this dog, this little dog that I rescued that had been beat up and stuff. And um that dog was never right. It was it had been so abused that basically it started out by biting you, right? And that's what that's what happens when you hurt a animal, you know, when you take it past the edge. Of course, then then you take it even further and you have learned helplessness where you just sit and don't do anything. It was tragic. Um I couldn't get that dog to lighten up those cats and but her world was inverted permanently. Had just been completely inverted. Up was down, down was down was up. Basic safety was reward. Uh-huh. Everything else, you were in an emergency state. It's just a lot easier as a as a behavioral commitment to just start out by biting because you're going to have to bite at some point anyway. And yeah, well, I think we've all known some people like this. And it's it's tragic to see. Yeah. hurt. People have a and and um it's interesting as we get more and more knowledge about how to hack that and intervene on that that um it'd be nice to be able to fix people like that. I think they would like to be fixed. I think of some people I know um a cousin in particular. Um drugs of abuse, you know, do this to people. They just, you know, they get people into these states where they just um people make decisions that they know are going to lead to, you know, they've done it before and they're just going to go down the hole again. I have lots of family members where that would be true. I think nowadays we all know or or are aware of people that did that because of the incredible expansion of availability of drugs of abuse including prescription drugs. Um I think if I may, I just want to just to make sure that I'm I'm staying oriented here. Here's where we've gotten. It seems dopamine encodes positive expectation and rewards and it's graded. You can have low levels, medium or high levels depending on how much positive anticipation. Um serotonin seems to encode negative events. Um if a human or an animal um sadly uh is raised in conditions or spends enough time in conditions where true rewards aren't there and survival itself becomes the reward, the dopamine system…

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