Dr. Read Montague on Huberman Lab: How dopamine learns

1. 0:00 – 2:54

   Read Montague

   1. RMDr. Read Montague0:00

      If any goal that you achieved, whatever it is, taking a drug, eating a food, um, 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. [upbeat music]

   2. AHAndrew Huberman0:24

      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 ophthalmology at Stanford School of Medicine. My guest today is Dr. Read Montague. Dr. Read Montague 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 neuromodulators 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 Read 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, et cetera, 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 seesaw 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 Read 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 neuromodulators 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

2. 2:54 – 8:49

   Dopamine, Motivation & Learning

   1. AHAndrew Huberman2:54

      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 zero cost 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. Read Montague. Dr. Read Montague, great to see you after all these fifteen years.

   2. RMDr. Read Montague3:22

      Fifteen years, um, you turned us down for a job offer then.

   3. AHAndrew Huberman3:26

      I did, um, but we both turned out okay, so-

   4. RMDr. Read Montague3:29

      Well, I hope so.

   5. AHAndrew Huberman3:30

      Yeah.

   6. RMDr. Read Montague3:30

      We'll see.

   7. AHAndrew Huberman3:31

      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 then maybe, uh, your athletic life a little bit later, but I wanna 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, [lips smack] such as motivation, movement, et cetera. How do you think about dopamine, the neuromodulator? 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?

   8. RMDr. Read Montague4:17

      Ah, 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 un- 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.

   9. AHAndrew Huberman5:12

      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?

   10. RMDr. Read Montague5:24

       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 thirty years. The algorithms are well understood. What wasn't well understood thirty years ago was the kind of remarkable things those same algorithms can learn. I, I'll come back to that.

   11. AHAndrew Huberman6:41

       Mm-hmm.

   12. RMDr. Read Montague6:41

       I mean, there've been a, 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 an area of science, and so what happens when you have a, a big finding, and it 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, in 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-- uh, the example is the, uh, so today is Wednesday. Suppose, and this is Rich Sutton's example. Suppose I make a prediction today that it's gonna rain two inches on Saturday, okay? Now, we're gonna fast-forward to tomorrow, and I'm gonna update my prediction because I have new knowledge, and it's gonna say, "I mean, it's gonna rain ten inches on Saturday." Okay, there's been no reinforcing feedback. It hasn't rained yet, 'cause it's not 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, a 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, forty 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 gonna 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

3. 8:49 – 12:24

   Reward Prediction Error, Expectations

   1. RMDr. Read Montague8:49

      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 to position, but you're learning, and dopamine is encoding those signals.

   2. AHAndrew Huberman9:12

      I'm so glad you said the word foraging, 'cause I want to hover on the theme of foraging, uh, in the context of human decision-making and learning and behavior. [lips smack] 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. [chuckles] Uh, they want to go to the beach on Saturday.

   3. RMDr. Read Montague9:35

      Mm-hmm.

   4. AHAndrew Huberman9:36

      Now, we can talk about re- reward prediction error, right? The difference between the expectation when it actually happens.

   5. RMDr. Read Montague9:41

      Okay, let me, let me interrupt-

   6. AHAndrew Huberman9:42

      Mm-hmm

   7. RMDr. Read Montague9:42

      ... 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.

   8. AHAndrew Huberman9:59

      Mm-hmm.

   9. RMDr. Read Montague9:59

      It may be positive, negative, or zero.

   10. AHAndrew Huberman10:01

       Mm-hmm.

   11. RMDr. Read Montague10:01

       And what you do is you make an error there. That was understood in the '60s and '70s. It's called the Rescorla-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. Th- 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 our learning rule." Obviously, it's a learning rule with an outcome when you get an outcome, when it's not zero, but it's successive predictions. It's like s- 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 bee brains, uh, sea 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-

   12. AHAndrew Huberman11:08

       Yeah

   13. RMDr. Read Montague11:08

       ... which is s- people say in a kind of, uh, vernacular way, "Oh, it's the difference between your expectations and your 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 DeepMind guys in London, who s- beat the world Go playing champion and made AlphaFold 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, uh, the players, the 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're, they threw other tricks into it. I'm not gonna get technical about it.... So there's a difference. It's not just expectation and outcome, it's expectation, next expectation, current outcome.

   14. AHAndrew Huberman12:14

       Mm-hmm.

   15. RMDr. Read Montague12:15

       And that is what rolls through, and that is what we see installed. And we have a paper, uh, this week coming out on honeybee brains, where you can show

4. 12:24 – 14:54

   Sponsors: David & Joovv

   1. RMDr. Read Montague12:24

      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 neuromodulators-

   2. AHAndrew Huberman12:38

      Sure

   3. RMDr. Read Montague12:38

      ... like that-

   4. AHAndrew Huberman12:39

      Sure

   5. RMDr. Read Montague12:39

      ... are fluctuating with learning and motivation, and it's probably the whole symphony of them that creates motivation states and things like that.

   6. AHAndrew Huberman12:48

      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 twenty grams of protein, only one hundred and fifty 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, et cetera, 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 one gram of protein per pound of body weight, and that allows me to take in the protein I need without consuming excess calories. I love all the David Bronze Bar flavors, including cookie dough, caramel chocolate, double chocolate, peanut butter chocolate. They all actually taste like candy bars. Again, they're amazing, but again, they have no sugar, and they have twenty grams of protein with just one hundred and fifty calories. If you'd like to try David, you can go to davidprotein.com/huberman. Right now, David is offering a deal where if you buy four cartons, you get the fifth carton for free. You can also find David on Amazon or in stores such as Target, Walmart, and Kroger. Again, to get the fifth carton for free, go to davidprotein.com/huberman. Today's episode is also brought to us by Joovv. Joovv makes medical-grade red light therapy devices. Now, if there's one thing that I have consistently emphasized on this podcast, it is the incredible impact that light can have on our biology. Now, in addition to sunlight, red light and near-infrared light sources have been shown to have positive effects on improving numerous aspects of cellular and organ health, including faster muscle recovery, improved skin health and wound healing, improvements in acne, reduced pain and inflammation, even mitochondrial function, and improving vision itself. What sets Joovv lights apart and why they're my preferred red light therapy device is that they use clinically proven wavelengths, meaning specific wavelengths of red light and near-infrared light in combination to trigger the optimal cellular adaptations. Personally, I use the Joovv whole body panel about

5. 14:54 – 23:36

   Foraging, Dating, Expectations vs Outcomes; AI

   1. AHAndrew Huberman14:54

      three to four times a week, and I use the Joovv handheld light both at home and when I travel. If you'd like to try Joovv, you can go to Joovv, spelled J-O-O-V-V, .com/huberman. Joovv is offering an exclusive discount to all Huberman Lab listeners with up to four hundred dollars off Joovv products. Again, that's Joovv, spelled J-O-O-V-V, .com/huberman to get up to four hundred dollars off. Okay, so I want to pin up a f- a few rules, uh, so that, um, people can move along this because I think, um, most people, a- 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-

   2. RMDr. Read Montague15:40

      Outcome

   3. AHAndrew Huberman15:40

      ... or lack of reward, expectation and outcome. So r- 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 gonna have a great meal someplace, and it 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, uh, on the dating market now. She will occasionally call me and ask me, you know, like: "How do I decode [chuckles] 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?" I'm like: "All right, well," you know, and I give my, my interpretation. I say, "Well, you know, it'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 gonna say I'm always right, but almost inevitably, it's three days later or three weeks later, it's like, "Oh, my goodness, how do I get out of this thing [chuckles] , 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.

   4. RMDr. Read Montague17:47

      Mm-hmm.

   5. AHAndrew Huberman17:48

      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 i- 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 gonna go. Then finds out, it, as life goes, that, "Oh, they're not perfect. There's this thing. Can I live with that?" So there, the, I- thinking of this as, like, a sawtooth of dopamine-

   6. RMDr. Read Montague18:21

      Mm-hmm

   7. AHAndrew Huberman18:21

      ... going through their system. Is that statement accurate, that dopamine and other neuromodulators are encoding the sort of expectation of success or lack of success, without actually knowing what the final endpoint is?

   8. RMDr. Read Montague18:33

      It's 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 Dayan when I was a postdoc, and we both arrived at the Salk 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 Y, that's less. You expected it to be low, it was more, that's, uh, but that's really rare.

   9. AHAndrew Huberman19:09

      I studied hard, I wanted an A, I got an A minus.

   10. RMDr. Read Montague19:12

       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.

   11. AHAndrew Huberman19:36

       Mm-hmm.

   12. RMDr. Read Montague19:37

       You, you, you have an expectation for an outcome, and either high or low of that, every learning rule should do that, and the psychologists had that f- kind of figured out 40 years ago, 50 years ago. But it doesn't quite work, 'cause 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, on an outcome, and I use the a- r- expectation outcome learning rule, it won't chain back to something that predicts a light. Suppose a sound [snaps fingers] 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.

   13. AHAndrew Huberman20:15

       It's Pavlovian.

   14. RMDr. Read Montague20:16

       Yeah, but those learning rules won't do that. They learn the wrong thing. They just do. It's just not well appreciated. Now-

   15. AHAndrew Huberman20:23

       Mm-hmm

   16. RMDr. Read Montague20:23

       ... back when we were trying to associate that learning rule with dopamine, there was [lip smack] 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 advisor, Terry Sejnowski, who's been on your show, I think he said something like, "There are these diffuse ascending systems that deliver these transmitters. You guys go work on that." [chuckles]

   17. AHAndrew Huberman20:51

       Sounds like-

   18. RMDr. Read Montague20:52

       Yeah

   19. AHAndrew Huberman20:52

       ... like Terry.

   20. RMDr. Read Montague20:52

       And he just sort of- [chuckles]

   21. AHAndrew Huberman20:53

       Love Terry.

   22. RMDr. Read Montague20:53

       And he just-

   23. AHAndrew Huberman20:53

       And his episode was spectacularly received.

   24. RMDr. Read Montague20:55

       Oh, great!

   25. AHAndrew Huberman20:56

       Yeah.

   26. RMDr. Read Montague20:56

       Well, I mean-

   27. AHAndrew Huberman20:56

       People love Terry

   28. RMDr. Read Montague20:56

       ... he, he was, it was the most open-

   29. AHAndrew Huberman20:58

       Mm-hmm

   30. RMDr. Read Montague20:59

       ... inviting environment, but of course, all the problems given out were impossible to solve, and I, I remember just thinking, "What?" Uh, but, um, the first, um, inroad was realizing that it w- 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 '84. Um, I was d- we were doing this in 1990, and we ran into a guy's data on dopamine, it's like looking at Wolfram 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 gonna 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 gonna fire, when they're gonna 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 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. [chuckles]
6. 23:36 – 29:58

   Dopamine, Expectation, Motivation; Forward Drive; Dopamine “Hits”

   1. RMDr. Read Montague23:37

      They've f- now been externalized and put into a computer program that now does things that supersede us. It's a little interesting convergence. Um, 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 Drosophila and whatnot, so.

   2. AHAndrew Huberman24:00

      Okay, so a couple of things. Uh, one, comment, and, uh, couple questions. Uh, first comment, um, I'm just gonna say, uh, so that you don't feel you have to, um, everyone should know that when Read says dopamine is responsible for X, Y, and Z, there are many other-... chemicals in the brain likely involved as well. Uh [clears throat]

   3. RMDr. Read Montague24:22

      Other chemicals, and dopamine has multiple functions.

   4. AHAndrew Huberman24:25

      Yeah. Yeah, I, I just want-

   5. RMDr. Read Montague24:27

      Like anything in biology.

   6. AHAndrew Huberman24:27

      Yeah, we should just embed, that's up on the chalkboard now, so that i- if you wanna 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.

   7. RMDr. Read Montague24:43

      Yeah.

   8. AHAndrew Huberman24:43

      Dopamine is clearly a major player. I wanna step back to a, um, [tsks] a human example, a non-AI 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 brainstem are using to deploy dopamine.

   9. RMDr. Read Montague25:05

      Which I, I don't know of an example like that in the world. Do you?

   10. AHAndrew Huberman25:10

       I don't. I mean, I can-

   11. RMDr. Read Montague25:11

       Where we've discovered the nature of an algorithm, once we externalize it-

   12. AHAndrew Huberman25:14

       Mm-hmm

   13. RMDr. Read Montague25:15

       ... we write code, and then it takes a few very special groups to all of a sudden have giant breakthroughs using that same algorithm.

   14. AHAndrew Huberman25:22

       Mm-hmm.

   15. RMDr. Read Montague25:23

       And those breakthroughs are gonna end up pumping information in, back into our head, and so we live in an intr- it's an interesting recursion there.

   16. AHAndrew Huberman25:32

       Mm-hmm.

   17. RMDr. Read Montague25:33

       Um, I don't know what will come about.

   18. AHAndrew Huberman25:34

       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.

   19. RMDr. Read Montague25:48

       Yeah.

   20. AHAndrew Huberman25:48

       And I think it's a little scary, but I wanna shelve that for, for la-

   21. RMDr. Read Montague25:50

       It is a little scary

   22. AHAndrew Huberman25:51

       ... later in the discussion.

   23. RMDr. Read Montague25:52

       Okay.

   24. AHAndrew Huberman25:52

       I, I wanna return to, um, [tsks] the dating example.

   25. RMDr. Read Montague25:56

       You're gonna hang this dating example around my neck, aren't you? [chuckles]

   26. AHAndrew Huberman25:58

       No, I think that, um, and, and we can, uh, partner it with another example, which would be-

   27. RMDr. Read Montague26:02

       Dating example is good. You, 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 coworker 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 view of it.

   28. AHAndrew Huberman26:22

       Changes your, 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?

   29. RMDr. Read Montague26:47

       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 Botvinick, 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, a- across those kinds of signals?

   30. AHAndrew Huberman27:18

       Mm-hmm.
7. 29:58 – 34:36

   Baseline Dopamine & Fluctuations; Parkinson’s Disease

   1. RMDr. Read Montague29:58

      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.

   2. AHAndrew Huberman30:22

      ... I'm gonna 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, a drug of, of abuse, like methamphetamine or something, but, you know, we throw a little bit of a dopaminergic stimulant into the picture. Does that just raise the, the kind of the height of the sawtooth? 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 p- it's now there's an association with this person or an event, but let's say that they're flooded with dopamine. Let's take a drug out of the picture. The dr- the, the experience generated more dopamine. Does it shape their expectation and motivation around that person?

   3. RMDr. Read Montague31:24

      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, phasic question.

   4. AHAndrew Huberman31:34

      Can you explain tonic? Most people are gonna think gin and tonic.

   5. RMDr. Read Montague31:36

      I will, I will. 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-

   6. AHAndrew Huberman31:54

      Yeah

   7. RMDr. Read Montague31:54

      ... dopamine.

   8. AHAndrew Huberman31:55

      Or they went to a play, and it sucked.

   9. RMDr. Read Montague31:57

      Yeah. It's disappointing, or it's sad-

   10. AHAndrew Huberman31:59

       He's got bad taste.

   11. RMDr. Read Montague32:01

       Y- yeah, yeah.

   12. AHAndrew Huberman32:02

       Yeah.

   13. RMDr. Read Montague32:02

       It just runs in your mind, and so, so, so that can lower the levels, and that changes the way in which, um, [lips smack] 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 seventy to seventy-five percent of your dopamine neurons in your brain stem. Those are only source of dopamine in your brain, except for a tiny pathway in your hypothalamus and pituitary axis.

   14. AHAndrew Huberman32:30

       A couple in the retina.

   15. RMDr. Read Montague32:32

       Well, there's-

   16. AHAndrew Huberman32:32

       Sorry.

   17. RMDr. Read Montague32:32

       Yeah.

   18. AHAndrew Huberman32:33

       The retinal biologist in me. Yep, they, they're doing things totally unrelated to any of this.

   19. RMDr. Read Montague32:36

       Yeah.

   20. AHAndrew Huberman32:36

       They're controlling adap- like, adaptational light levels.

   21. RMDr. Read Montague32:38

       Yeah, light level adaptations-

   22. AHAndrew Huberman32:39

       Yeah

   23. RMDr. Read Montague32:39

       ... and, um, certainly in goldfish.

   24. AHAndrew Huberman32:41

       Yeah.

   25. RMDr. Read Montague32:42

       Uh, um, yeah, those are actually very interesting. [laughing]

   26. AHAndrew Huberman32:46

       We'll get back to those.

   27. RMDr. Read Montague32:46

       I won't talk, I won't talk about them.

   28. AHAndrew Huberman32:47

       So you had the, the dopaminergic brainstem neurons that degenerate in, uh, Parkinson's.

   29. RMDr. Read Montague32:51

       By the time you're feeling so stiff, uh, y- y- starting to have tremors, all, all the parts, the flat facey, flat affect, and, um, [lips smack] and somebody gets you to a doctor, you're, you're in the seventy to seventy-five percent loss, okay?

   30. AHAndrew Huberman33:10

       Mm-hmm.
8. 34:36 – 42:29

   Movement, Urgency; ADHD, Bee’s Dance, Explorer vs Focus Mode

   1. RMDr. Read Montague34:36

      I've always thought about Parkinson's as an active freezing disease. The, the nervous system is doing exactly what it would do if... 'Cause it takes energy to transition from where you are to doing the next thing. S- 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 'cause it has to keep your behavior going, or else you're gonna die.

   2. AHAndrew Huberman35:00

      I don't think it's a coincidence, uh, in fact, I know it's not, that dopamine is involved in learning, motivation, feelings, and movement, among a few other m- 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, w- a- and what you're referring to as the tonic kind of, um, baseline, what I call baseline levels of dopamine-

   3. RMDr. Read Montague35:32

      Mm-hmm

   4. AHAndrew Huberman35:33

      ... as opposed to spikes on top of that, um, predict whether or not you'll move forward, w- uh, how much re- 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, 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, we're procrastinating. Whereas motivation is this just kinda, like, catch-all term for how motivated are you and anything like that, 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-making in a particular direction?

   5. RMDr. Read Montague36:47

      We exactly think that.

   6. AHAndrew Huberman36:48

      Okay, thank you. I wasn't asking you to validate my, my non-theory theory. I just w- 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 key role.

   7. RMDr. Read Montague37:00

      It, it's very clear dopamine and the other neuromodulators 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 a brain state is kind of hold onto it a bit. It's got to have a dwell time, right?

   8. AHAndrew Huberman37:19

      Mm-hmm.

   9. RMDr. Read Montague37:19

      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 tied 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 awry, where you keep feeding a system, um, uh, a level of dopamine by putting a drug in that c- blocks its reuptake, that it can't anticipate right, and so it keeps chasing that, and it never gets there.

   10. AHAndrew Huberman38:51

       When people have ADHD, even low, w- 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, 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 dopaminergic systems are dysregulated. These drugs, almost all of them, right, whether or not it's Ritalin or Adderall or these other drugs, they raise levels of dopamine and norepinephrine-

   11. RMDr. Read Montague39:38

       Oh, yes

   12. AHAndrew Huberman39:38

       ... 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.

   13. RMDr. Read Montague39:48

       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.

   14. AHAndrew Huberman39:58

       Does that surprise you-

   15. RMDr. Read Montague39:59

       No

   16. AHAndrew Huberman39:59

       ... that increasing dopamine would do that?

   17. RMDr. Read Montague40:01

       No. Bees do this. Okay, so when you're a forager bee, uh, a, a, you come back and you do a little dance in the hive, and it tells the hive, uh, f- other foragers where to go find the nectar source.

   18. AHAndrew Huberman40:13

       Mm-hmm.

   19. RMDr. Read Montague40:14

       Okay, and it's a, it's a whole language. People have worked that out. It tells you, "Fly this far w- with the sun here, and there's a polarization"-

   20. AHAndrew Huberman40:21

       It's an amazing phenomenon.

   21. RMDr. Read Montague40:22

       Yeah. Yes, it is.

   22. AHAndrew Huberman40:23

       That the bees go back, and they literally, they do this dance, the waggle dance.

   23. RMDr. Read Montague40:26

       And they feel the, the, the waggle dance on the bee, and by feeling it, they know where to go. They-

   24. AHAndrew Huberman40:32

       Wild.

   25. RMDr. Read Montague40:33

       Well, it's a language. You can deco- I mean, it's been decoded-

   26. AHAndrew Huberman40:35

       Yeah, it's very cool

   27. RMDr. Read Montague40:36

       ... to some degree.

   28. AHAndrew Huberman40:37

       Yeah. Yeah.

   29. RMDr. Read Montague40:37

       When you look at bees, I know this because I've been working with a bee guy, Brian Smith, at Arizona State University for, uh, the last few years. I've known him my whole career, but I've, I've... Now he 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.

   30. AHAndrew Huberman41:05

       Mm-hmm.
9. 42:29 – 43:40

   Sponsor: AG1

   1. RMDr. Read Montague42:29

      and, uh, you know, and 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.

   2. AHAndrew Huberman42:38

      Mm-hmm.

   3. RMDr. Read Montague42:38

      You need all that. And this distribution of abilities-... it's 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, "M- w- what about this little wiggle?" It's, it's the wiggle in our software design for motivation and learning.

   4. AHAndrew Huberman42:55

      Mm-hmm.

   5. RMDr. Read Montague42:56

      Um, it's very effective-

   6. AHAndrew Huberman42:58

      Mm-hmm

   7. RMDr. Read Montague42:58

      ... to sometimes be the explorer, and other times, you have to be able to f- follow the chain of, "This is gonna lead you to the thing that you want. Stay on course."

   8. AHAndrew Huberman43:13

      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's 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

10. 43:40 – 50:54

    Social Media, ADHD; Explorers vs Task-Based, Combat

    1. AHAndrew Huberman43:40

       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 drinkag1.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, uh, 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, s-

    2. RMDr. Read Montague44:31

       Or task-based.

    3. AHAndrew Huberman44:33

       Task-based.

    4. RMDr. Read Montague44:33

       They can really, uh, form a task, hold it in mind. A task stays there.

    5. AHAndrew Huberman44:39

       Mm-hmm.

    6. RMDr. Read Montague44:39

       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 wanna be in two years. Okay, to get there, I'm gonna have to do... You know, I'm gonna have to crawl through, you know, hell to get there in two years, and I have to do these things, and I'm gonna 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, s- six months into that, you decide you wanna go do ice hockey, well, that's a problem. That's a person who can't-

    7. AHAndrew Huberman45:12

       Mm-hmm

    8. RMDr. Read Montague45:14

       ... can't focus down.

    9. AHAndrew Huberman45:14

       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 wanna knock it. I teach and learn on social media. I, what I m- mainly thinking about is, um, [lips smack] 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, 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 stimuli, like you get when you scroll, uh, a TikTok 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 en 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.

    10. RMDr. Read Montague46:36

        Yeah, you build your ADHD muscle.

    11. AHAndrew Huberman46:38

        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?

    12. RMDr. Read Montague46:59

        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 over-train on some, on one of these two possibilit- if we're gonna divide these two possibilities, chase a goal, chase everything that flies along, right?

    13. AHAndrew Huberman47:16

        Mm-hmm.

    14. RMDr. Read Montague47:16

        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 where being ADD is an absolute requirement. [chuckles]

    15. AHAndrew Huberman47:34

        Can you give me a few examples?

    16. RMDr. Read Montague47:35

        Combat.

    17. AHAndrew Huberman47:36

        Hmm.

    18. RMDr. Read Montague47:37

        Combat, rapid decision-making, kind of the fighter pilot, uh, uh, situational knowledge. Now, w- what do they do to prepare for that? Uh, 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 then, you know, they str- 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.

    19. AHAndrew Huberman48:13

        That'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.

    20. RMDr. Read Montague48:44

        Anytime you have to do rapid-fire decision-making, I think you would want somebody who is able to at least train up-... to that level there.

    21. AHAndrew Huberman48:52

        Do you worry about the overexposure to, um, you know, -

    22. RMDr. Read Montague48:58

        These-

    23. AHAndrew Huberman48:58

        Frequent media-

    24. RMDr. Read Montague49:00

        Yeah, the short media.

    25. AHAndrew Huberman49:01

        Uh, content? Yeah.

    26. RMDr. Read Montague49:01

        I have a lot of kids, and so, uh, 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, uh, y- y- you know, and basically, my kids are smarter than me, and they're, they're more nimble, and they, they move faster than [chuckles] I can. 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-

    27. AHAndrew Huberman49:34

        Mm-hmm

    28. RMDr. Read Montague49:34

        ... 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." Po- p- I mean, it, it's mind-numbing to me, right?

    29. AHAndrew Huberman49:46

        Well, there isn't a lot of long-term learning. I... You know, one of the things that I define learning by is, 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, 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, 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.

    30. RMDr. Read Montague50:20

        [chuckles]
11. 50:54 – 1:01:36

    Effort, Learning; Social Media & Phones, Resisting Behaviors

    1. AHAndrew Huberman50:54

       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.

    2. RMDr. Read Montague51:09

       It takes a while to read a book.

    3. AHAndrew Huberman51:11

       Mm-hmm.

    4. RMDr. Read Montague51:11

       That's the thing. You... It takes a deliberative set of intentional actions to read a book. That's the difference in the modality.

    5. AHAndrew Huberman51:18

       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?

    6. RMDr. Read Montague52:15

       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. L- 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 'cause it slows you down. I don't know whether effort is itself the cause or whether the fact that effort is slow-

    7. AHAndrew Huberman52:40

       Mm-hmm

    8. RMDr. Read Montague52:40

       ... and so it slows it down. So may-

    9. AHAndrew Huberman52:42

       We could do- we could design an experiment to separate-

    10. RMDr. Read Montague52:43

        Yeah, maybe slowing it down-

    11. AHAndrew Huberman52:44

        ... effort and speed

    12. RMDr. Read Montague52:45

        It, it, it immediately gave me this idea.

    13. AHAndrew Huberman52:48

        Mm.

    14. RMDr. Read Montague52:49

        Um, so that's true in s- 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-

    15. AHAndrew Huberman53:01

        Mm-hmm

    16. RMDr. Read Montague53:01

        ... very well. And the, you know, even the rodents that can read are kind of flat affectively and all. I mean, rodent is a terrible model for this, really.

    17. AHAndrew Huberman53:08

        Mm-hmm.

    18. RMDr. Read Montague53:08

        I, I, I, I wouldn't even do the experiment on a rodent. I'd do the experiment on a human-

    19. AHAndrew Huberman53:11

        Yeah

    20. RMDr. Read Montague53:12

        ... where you can, with a few words, set a human in a certain state and, you know, go out, 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 th- th- th- the generation we're concerned about... I've just read this book, The Anxious Generation.

    21. AHAndrew Huberman53:35

        Oh, yeah, Jonathan was on this podcast.

    22. RMDr. Read Montague53:37

        And I was on a MacArthur network, um, neuroscience and law with him for a while, and he, he's just a v- extremely clear-headed 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 them 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, it's like we're trying to hold back a tsunami. I mean, it's just the water is going past us, and so I, I think the only way to, uh, deal with it is kind of fly by wire. Um, w- you know, when a little fire starts over here, and somebody says, "Oh, this really causes a depression and mood," and it's these features of it, then we can go react to that and all, but it, it's very hard to know what it's gonna do globally. It's, it's, it's, it's evolving with its own... It feels like it's independent-

    23. AHAndrew Huberman54:49

        Mm-hmm

    24. RMDr. Read Montague54:49

        ... of anything we do, and so I, I, I, I think it's gonna have to be a react- uh, 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, uh, 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 f- the raw fact was, uh, she, "I'm being left out of all the discussions and whatnot." I mean, the, the answer was that that is true. She is being left out. Their, their, uh, 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, and so, um, uh, Jonathan has real prescriptions for how to fix that. He has good suggestions for how to fix that, but, uh, 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.

    25. AHAndrew Huberman56:04

        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 y- I could click entertainment, and 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 differ- a couple of different lenses. We're obviously not gonna solve this problem. I am curious about speed versus effort when foraging. Uh, let's take it back to the dating example. This person's gonna kill me for, uh, I'm not gonna 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 kinda s- kind of ends up in the same place, where you're like, 'Ugh, 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 over time," you know? So, um, we can change our, our mode of foraging. Uh, 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.

    26. RMDr. Read Montague57:37

        You do that to yourself?

    27. AHAndrew Huberman57:38

        I do, and not because-

    28. RMDr. Read Montague57:39

        You're like the person that can't avoid eating the chocolate cake.

    29. AHAndrew Huberman57:41

        No, it, it-

    30. RMDr. Read Montague57:41

        You lock the chocolate cake up
12. 1:01:36 – 1:11:21

    Serotonin & Dopamine, Opponency, SSRIs

    1. RMDr. Read Montague1:01:36

       Um, and it's off. It's off. See, fant- the be- well, I like the head of school.

    2. AHAndrew Huberman1:01:42

       Mm-hmm.

    3. RMDr. Read Montague1:01:43

       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 gonna let these kids interface with these systems that are smarter than us? More interesting, no less. [chuckles]

    4. AHAndrew Huberman1:02:01

       I want to talk about AI, um, but before we go there, um, I think, uh, 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 [chuckles] 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 seem-- these are some interesting data.

    5. RMDr. Read Montague1:02:42

       In human studies, too.

    6. AHAndrew Huberman1:02:43

       Great, so educate us about serotonin in this context-

    7. RMDr. Read Montague1:02:47

       Okay

    8. AHAndrew Huberman1:02:47

       ... because I know it's a huge topic, right?

    9. RMDr. Read Montague1:02:49

       A habit that people that work on neuromodulators, I'll name a few, dopamine, serotonin, norepinephrine, acetylcholine, histamine, um, [lips smack] probably on the order of, let's say, fifteen to twenty-

    10. AHAndrew Huberman1:03:03

        Mm

    11. RMDr. Read Montague1:03:03

        ... I'd 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. Epine-- norepinephrine and epinephrine are, uh, uh, 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 ch- it's a rodent. Uh, they see the cheese, they want the cheese, [lips smack] but the light is on. That means that the grid 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's learning about positive things or the absence of negative things or the-

    12. AHAndrew Huberman1:04:07

        Mm.

    13. RMDr. Read Montague1:04:07

        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, uh, only group who record subsecond 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, um, [lips smack] 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, an opponency to that. Um, at your own institution, Rob Malenka has a, a, a set of beautiful results in rodents, where the learning that they see in the animal requires that kind of opponency, and so, 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. There are old ideas, uh, from the '60s and '70s, about opponent systems in this sort of affective processing space. Dopamine has now inherited the positive part of that and serotonin, the negative part of that. Opponency, 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, [lips smack] you prevent, uh, ser- selective serotonin reuptake inhibitors-

    14. AHAndrew Huberman1:06:19

        Prozac

    15. RMDr. Read Montague1:06:20

        ... Prozac, fluoxetine, uh, Lexapro. Um, it blocks the reuptake 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. Uh, it's very heterogeneous, um, but it pushes serotonin into the dopamine terminals, too. This is less well understood.

    16. AHAndrew Huberman1:06:43

        Hmm.

    17. RMDr. Read Montague1:06:44

        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 gonna chatter for positive things. You might start negatively conditioning on things that you should actually pursue and learn about.

    18. AHAndrew Huberman1:07:04

        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 anhedonia, 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 acr- uh, 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?

    19. RMDr. Read Montague1:07:47

        Well, the idea would be it makes you less likely to code something as negative-

    20. AHAndrew Huberman1:07:51

        Okay, so-

    21. RMDr. Read Montague1:07:51

        -because you have less serotonin in the serotonergic terminals.

    22. AHAndrew Huberman1:07:55

        Mm-hmm.

    23. RMDr. Read Montague1:07:55

        And so if they're communicating this information about learning about-

    24. AHAndrew Huberman1:07:59

        More serotonin in the serotonergic terminals?

    25. RMDr. Read Montague1:08:02

        Yep.

    26. AHAndrew Huberman1:08:02

        Gotcha. So if somebody takes a, 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?

    27. RMDr. Read Montague1:08:27

        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, s- will also bind to serotonin and suck it out. Not quite as well, 'cause 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, the serotonin in the serotonin terminals by blocking the reuptake.

    28. AHAndrew Huberman1:09:12

        I see. So that's why you said it earlier. I tried to correct you, saying, "No, it's gonna 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-

    29. RMDr. Read Montague1:09:25

        Correct

    30. AHAndrew Huberman1:09:26

        ... when serotonin is-
13. 1:11:21 – 1:18:34

    Hunger, Dopamine; Negative Feedback, Learning, Trauma; Torture

    1. AHAndrew Huberman1:11:21

       going down.

    2. RMDr. Read Montague1:11:21

       Yes. Right.

    3. AHAndrew Huberman1:11:22

       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?

    4. RMDr. Read Montague1:11:33

       Yes.

    5. AHAndrew Huberman1:11:34

       Interesting.

    6. RMDr. Read Montague1:11:34

       Yeah, and then there's state changes-

    7. AHAndrew Huberman1:11:36

       Mm-hmm

    8. RMDr. Read Montague1:11:36

       ... in your brain that can be induced by, for example, making somebody hungry-

    9. AHAndrew Huberman1:11:39

       Mm-hmm

    10. RMDr. Read Montague1:11:40

        ... where we don't really know how to explain what we're seeing, but they still show opponency.

    11. AHAndrew Huberman1:11:45

        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?

    12. RMDr. Read Montague1:11:56

        No. No, not in rodent, in rodent model. I can talk about rodent models. We're actually in the middle of doing something like that now, where people come in in the morning, hungry. Uh, uh, i- 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 gonna eat, and then we repeat the experiment after they've eaten. But in rodents, it's very clear, uh, I guess at the l- level of the amygdala, if you make a rodent hungry, then you can show that dopamine will encode, um, something like punishment prediction error, it's not reward prediction error. In other words, it does- it's like it flips its role. It's like if you're in a-

    13. AHAndrew Huberman1:12:37

        How hungry do you have to be?

    14. RMDr. Read Montague1:12:38

        I don't know how it feels to be a hungry rat, but, um, imagine that it put it in an emergency state.

    15. AHAndrew Huberman1:12:46

        Okay, so it's not just a kind of like, like, me, I don't do any formal intermittent fasting, but I usually eat my first meal somewhere around, um, between 10:00 and noon. Uh, and at 9:00 a.m., I'm, like, mildly hungry. I could eat, but I'm not-

    16. RMDr. Read Montague1:12:59

        But by 4:00, you would be hungry.

    17. AHAndrew Huberman1:13:00

        I'd be really hungry.

    18. RMDr. Read Montague1:13:01

        You'd be pr- you'd feel it. You'd feel what we've all felt when we're hungry.

    19. AHAndrew Huberman1:13:04

        Mm-hmm.

    20. RMDr. Read Montague1:13:04

        And, um, this is a guy called Mark Anderman at Harvard?

    21. AHAndrew Huberman1:13:08

        Oh, yeah, I know Mark. Yeah.

    22. RMDr. Read Montague1:13:09

        So he puts animals in starvation states, and he shows that dopamine will encode aversive events, aversive errors.... very clear result.

    23. AHAndrew Huberman1:13:17

        So, folks-

    24. RMDr. Read Montague1:13:18

        I, I know this because he called me. I mean, we, we, we met, um-

    25. AHAndrew Huberman1:13:21

        So when your kid boyfriend or girlfriend is hungry, and you're going to a show, or you're going someplace, you gotta feed 'em 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-

    26. RMDr. Read Montague1:13:34

        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.

    27. AHAndrew Huberman1:13:52

        Very interesting. So general state of stress, 'cause hunger is a form of stress-

    28. RMDr. Read Montague1:13:58

        Yes

    29. AHAndrew Huberman1:13:58

        ... uh, drives the direction of the dopamine, um, to either reinforce positive things or reinforce negative things.

    30. RMDr. Read Montague1:14:09

        Yeah, 'cause think about it. If you get to a state where you're really starving, things have not been going well for a long time. Y- 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 gonna really sit around and wait for the, the rewards? The main thing you wanna 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 wanna do. You're in an emergency state, and you wanna use this reinforcement system, this expectation system, to stay alive. You wanna pay attention mainly to those things. You wanna pay attention to 'em, you wanna be motivated by 'em, you wanna be motivated and pay attention, and avoid the negative things. But that's an emergency state. When I talk to people about how, [lips smack] um, reinforcement learning models s- say, uh, have an impact on how you should train an animal, uh, i-i- typically, in my case, it's in a laboratory setting, but you could use this with, uh, other, uh, 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's shot beside you. That's negative feedback. What happens, you have, uh, 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 egress. This is the whole PTSD cycle, but that's rational. That's rational. That was a, th- that was an absolutely unexpected, cataclysmic event. You better... Y- and you don't know what could have caused it, really, um, as, as far as events leading to it, so you overgeneralize and all, and so you don't learn very well like that. So a- 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, it- 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 [chuckles] 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."
14. 1:18:34 – 1:19:48

    Drugs of Abuse & High Dopamine

    1. RMDr. Read Montague1:18:34

       know, the incremental removal of threat, um, given that you've made good on a, a little promise-

    2. AHAndrew Huberman1:18:39

       Mm-hmm

    3. RMDr. Read Montague1:18:39

       ... could be a lot. I, I mean, I-

    4. AHAndrew Huberman1:18:42

       Oh, I, I've, I've seen that.

    5. RMDr. Read Montague1:18:43

       That doesn't even have to be as extreme as torture.

    6. AHAndrew Huberman1:18:46

       Right.

    7. RMDr. Read Montague1:18:46

       Read, uh, Dostoevsky [chuckles] -

    8. AHAndrew Huberman1:18:48

       Yeah, sure

    9. RMDr. Read Montague1:18:48

       ... and family dy- read Dostoevsky and look at the family dynamics and go, "You know, they're dialing knobs on, you know, degrees of punishment, and, and, and it's very effective."

    10. AHAndrew Huberman1:18:58

        Let's take the inverse of this. Let's shine some light in the room, [chuckles] 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 v- uh, very high levels of dopaminergic 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 s- someone was saying, you know, at some point in the mid '80s, uh, it got a lot harder to, to make great music. And someone said, "What happened?" And they said, "Cocaine." Said, "Why would cocaine do that?" And he said, "Because it's a me drug."

    11. RMDr. Read Montague1:19:47

        Hmm.

    12. AHAndrew Huberman1:19:47

        Dopamine

15. 1:19:48 – 1:21:35

    Sponsor: Function

    1. AHAndrew Huberman1:19:48

       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, dopaminergic activities. Um, what does that do to the reward?

    2. RMDr. Read Montague1:20:02

       If you look at it on the average, it resets expectations where very few, if any, natural events can exceed them.

    3. AHAndrew Huberman1:20:12

       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. Function provides over one hundred advanced lab tests that give you a key snapshot of your entire bodily health. This snapshot offers you with insights on your heart health, hormone health, immune functioning, nutrient levels, and much more. They've also recently added tests for toxins, such as BPA exposure from harmful plastics, and tests for PFAS, or forever chemicals. Function not only provides testing of over a hundred biomarkers key to your physical and mental health, but it also analyzes these results and provides insights from top doctors who are expert in the relevant areas. For example, in one of my first tests with Function, I learned that I had elevated levels of mercury in my blood. Function not only helped me detect that, but offered insights into how best to reduce my mercury levels, which included limiting my tuna consumption, I'd been eating a lot of tuna, while also making an effort to eat more leafy greens and supplementing with NAC, N-acetylcysteine, both of which can support glutathione production and detoxification. And I should say, by taking a second Function test, that approach worked. Comprehensive blood testing is vitally important. There are so many things related to your mental and physical health that can only be detected in a blood test. The problem is, blood testing has always been very expensive and complicated. In contrast, I've been super impressed by Function's simplicity and

16. 1:21:35 – 1:27:34

    Trauma & Dopamine Adaptation

    1. AHAndrew Huberman1:21:35

       at the level of cost. It is very affordable. As a consequence, I decided to join their scientific advisory board, and I'm thrilled that they're sponsoring the podcast. If you'd like to try Function, you can go to functionhealth.com/huberman. Function currently has a waitlist of over two hundred and fifty thousand people, but they're offering early access to Huberman podcast listeners. Again, that's functionhealth.com/huberman to get early access to Function.

    2. RMDr. Read Montague1:22:00

       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 thirty cats."

    3. AHAndrew Huberman1:22:13

       Oh, my God!

    4. RMDr. Read Montague1:22:14

       They stayed outside.

    5. AHAndrew Huberman1:22:15

       Why?

    6. RMDr. Read Montague1:22:15

       That was back when animals, oh, I just kind of-

    7. AHAndrew Huberman1:22:17

       Thirty cats?

    8. RMDr. Read Montague1:22:18

       I had a cat, the cat had a litter. There were seven in the litter, they all survived. [laughing] Then, uh-

    9. AHAndrew Huberman1:22:25

       Ah, good for you, man.

    10. RMDr. Read Montague1:22:26

        I wasn't really a s- budding scientist then, but I realize in retrospect-

    11. AHAndrew Huberman1:22:30

        Mm

    12. RMDr. Read Montague1:22:30

        ... that I really watched them.

    13. AHAndrew Huberman1:22:31

        Mm-hmm.

    14. RMDr. Read Montague1:22:32

        Okay, and understood their behavior, and there was this dog, this little dog, that I rescued that had been beat up and stuff, and-

    15. AHAndrew Huberman1:22:38

        Mm

    16. RMDr. Read Montague1:22:39

        ... um, that dog was never right. It was s- 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.

    17. AHAndrew Huberman1:23:01

        It was tragic.

    18. RMDr. Read Montague1:23:02

        Um, I couldn't get that dog to lighten up with those cats and... But her world was inverted, permanently. Had just been completely inverted. Up was down, down was, uh, down was up.

    19. AHAndrew Huberman1:23:16

        Basic safety was reward.

    20. RMDr. Read Montague1:23:18

        Uh-huh.

    21. AHAndrew Huberman1:23:19

        Everything else above that was off the table.

    22. RMDr. Read Montague1:23:20

        You were in an emergency state. It's just a lot easier as a, as a behavioral commitment to just start out by biting, 'cause you're gonna have to bite at some point anyway.

    23. AHAndrew Huberman1:23:29

        Hmm.

    24. RMDr. Read Montague1:23:30

        And-

    25. AHAndrew Huberman1:23:31

        Yeah, well, I think we've all known some people like this-

    26. RMDr. Read Montague1:23:32

        Yeah

    27. AHAndrew Huberman1:23:33

        ... and it's, it's, it's tragic to see. Yeah.

    28. RMDr. Read Montague1:23:35

        Hurt people have a, uh... And, and, um, it's interesting, as we get more and more knowledge about how to hack that and intervene on that, that w-, 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, um, people make decisions that they know are gonna lead to... You know, they've done it before, and they're just gonna go down the hole again. I have lots of family members where that would be true.

    29. AHAndrew Huberman1:24:16

        I think nowadays we all know or, or are aware of people that-

    30. RMDr. Read Montague1:24:21

        Yes
17. 1:27:34 – 1:29:50

    SSRIs, Dopamine, Positive Experiences

    1. RMDr. Read Montague1:27:34

       probes that we have done, um, it's opponent, it's opponent. It, it is, uh, going the opposite direction. Some of the best data is from humans, not rodents. It's, it's a minority observation in rodents. I mean, they're- it's scattered.

    2. AHAndrew Huberman1:27:49

       Mm-hmm.

    3. RMDr. Read Montague1:27:49

       Um, it's quite hard to engineer the behavior in a rodent. I think it's, uh, uh-

    4. AHAndrew Huberman1:27:54

       Oh, I love that we're talking about humans. I mean, most people listening are interested in humans. Uh, I am totally fascinated to the point of being blown away by this SS- SSRI thing, that if serotonin reuptake inhibitors, uh, drive up serotonin, which they do, they prevent reuptake, that some of that serotonin gets into the dopamine synapses-

    5. RMDr. Read Montague1:28:15

       A lot of it does.

    6. AHAndrew Huberman1:28:16

       A lot of it does.

    7. RMDr. Read Montague1:28:17

       So it prevents re-

    8. AHAndrew Huberman1:28:17

       Why haven't we been told this? And then it lowers the rewarding properties of good stuff.

    9. RMDr. Read Montague1:28:23

       That's the best way to explain it. And, you know, it's science. Somebody doesn't think that's the explanation. But the fact is, when you put an SSRI on, the serotonin that's released, due to activity in serotonin neurons, it's not going back into serotonin terminals. Where does it go? This paper by John Dani in 2005 showed it goes into the dopamine system, and he knows that because he could block the dopamine reuptake-

    10. AHAndrew Huberman1:28:49

        Sure

    11. RMDr. Read Montague1:28:49

        ... and you, and it, it was a 40% difference. So there's all this serotonin sitting there in these terminals they're gonna be releasing. Now, that's the negative juice, let's say.

    12. AHAndrew Huberman1:28:59

        Mm-hmm.

    13. RMDr. Read Montague1:28:59

        Let's say that on the other side of this signaling pathway, um, electrical activity comes through, you release this transmitter, it has an impact, and the receiver goes, "Oh, I'm getting a lot of negative stuff here." But in fact, it's because it's sitting in neurons that chatter for positive things. [exhales] You would have a hard time learning about positive things. You might also register negative events as being rewarding, and you learn yourself into a kind of depression that way. That's an interesting set of possibilities, physical possibilities.

    14. AHAndrew Huberman1:29:29

        Mm-hmm.

    15. RMDr. Read Montague1:29:29

        Um, yeah, that was a fantastic paper. I don't know why it didn't sort of catch on. I think there, um, I don't remember, but I know John Dani quite well, and he did hard experiments, and they took a long time.

    16. AHAndrew Huberman1:29:42

        We'll put a reference to the paper. I think, uh, I'll answer my own question by saying that I think that really good scientific

18. 1:29:50 – 1:36:16

    Deep Brain Stimulation; Measuring Dopamine & Serotonin in Humans

    1. AHAndrew Huberman1:29:50

       findings and theories need advocacy to get lens-

    2. RMDr. Read Montague1:29:54

       They need a shepherd.

    3. AHAndrew Huberman1:29:55

       They need a shepherd. I mean, it's part of the reason I started the podcast and invite amazing guests like you and like Terry on, and people who really think deeply about the wh- the whole field. And, uh, you're changing the way that I think about serotonin, SSRIs, dopamine. You're expanding all of it, truly. Um, and I know for those listening, it's- that's also true. I know you're chomping at the bit to talk about learning algorithms and AI [laughing] , but I want to know first about the experiments where you stuck wires up people's noses and recorded-

    4. RMDr. Read Montague1:30:23

       Ah

    5. AHAndrew Huberman1:30:23

       ... uh, dopamine signals in their noses, because, um, these are wild and cool experiments.

    6. RMDr. Read Montague1:30:29

       They are, and they're not wild and cool because of me. They're wild and cool because of Cristina Zelano at Northwestern. But let me say one thing about how we do measure dopamine in human brains. We do it in very specialized circumstances, where you are having a deep brain stimulating electrode put into your brain to treat a movement disorder, like Parkinson's disease or essential tremors. So when you have that, and a minority of patients choose to have a small burr hole put in their head, and under careful, uh, operating room procedures, it's put down into different structures in your brain, we won't name them, and then turned on. Okay? And it's symptom relieving. Essential tremors is like Parkinson's disease. You have tremors, and you have difficulty with movement and whatnot. I don't think you have the emotional problems the Parkinson's patients do, but it's not Parkinson's. You have not lost dopamine. If you give an essential tremor patient, um, dopamine drugs, like they do Parkinson's patients, th- they get much worse, okay? The tremors are typically just really irritating for people, and so they do elective neurosurgery to have, uh, microwires put in their brain, and it's a very active area of clinical-... neuroscience and clinical treatment. Parkinson’s disease, also, you can have a stimulating electrode put in. When you do that, you put a little tiny, and I mean tiny, um, guide tube down, and they drop the electrodes in there, and under those circumstances, we ask to put, uh, an electrode in, equipped with a neural network model that knows how to interpret electrical signals on the electrode as dopamine, serotonin, norepinephrine, pH, and peroxide fluctuations. Um, [lips smack] this isn’t exactly, you know, you don’t go into Walmart and find this kind of stuff. I mean, the reason nobody’s heard about it is because it’s a very specialized area right on the edge of translational neuroscience, and so it’s there that we’ve gotten recordings from deep in the brain. What’s amazing is when you ask people: Would you let us piggyback on your electrodes? Because the electrodes that they use have research contacts, and we can make measurements of these transmitters without sitting on any of the clinical bandwidth. In other words, we don’t eat up any of the ability of the neurologist to use the electrode output, um, to make decisions about the [deep breath] treatment. Okay, there are a lot of moving parts in that. These, these are... I’ve been doing this for a while, and so for about the last twelve years, I’ve, I, I got very motivated to measure dopamine in human beings at timescales that were physiological and during cognitive events that we find meaningful. Okay, so it’s- I thought the method was very clever. I won’t even go into talking about the method. It kind of worked right away. Um, but the th- the entire process didn’t work right away, and it’s taken way over a decade. I mean, it took a lot of work. Um, so we have sites set up around the world where we do these things. Okay, it’s in that context that we have got knowledge about how to use these depth electrodes to, instead of just measuring electrical activity, to do neurochemistry. Okay. Then I ran into Christina Zelano, who’s an olfactory physiologist at Northwestern Uni- full, full professor at Northwestern University, very gifted. What Christina was doing was taking these depth electrodes that are FDA-approved, normally used to be put carefully down into the tissue of your brain, they’re basically just rubbery little tubes about a millimeter in diameter, and snaking it up people’s nose and just laying it up against a region of the olfactory epithelium, the part of your [sniffs] tissue inside your nose, way up high, basically around here.

    7. AHAndrew Huberman1:34:17

       Near your eyeball.

    8. RMDr. Read Montague1:34:18

       Uh, near your eyeball. Above your eyeball.

    9. AHAndrew Huberman1:34:20

       Above your eye, yeah.

    10. RMDr. Read Montague1:34:20

        Above and northwest of your eyeball, if you know how to put the-

    11. AHAndrew Huberman1:34:23

        [chuckles]

    12. RMDr. Read Montague1:34:23

        Okay. Um, and doing electrophysiology, listening to the electrical activity, and she already had, she had rodent model stuff that... Okay. And I went: I can totally get the chemistry off of that, and why is that important? Well, other than being weird, you can consent healthy people into doing this. You can snake this thing up there and clip it to their nostril, set up the electronics beside them, and then you can do all kinds of stuff, including letting them eat, letting them do mindfulness meditation, breathing exercises, uh, letting them do decision-making tasks with and without other people. You can do simple things like just a con- uh, uh, a stimulus, and then squirt odor in there, a rewarding smell.

    13. AHAndrew Huberman1:35:09

        And measure dopamine and serotonin.

    14. RMDr. Read Montague1:35:11

        Oh, yeah, and so we’re giddy about this, mainly because we can consent healthy people into doing this. One of the complaints, of course, of doing it in people with epilepsy and Parkinson’s and whatnot, is they have epilepsy and Parkinson’s. They have an affliction on board.

    15. AHAndrew Huberman1:35:26

        Could you just share with us, are there any, um, top contour statements that we can make about brain state, um, dopamine, and serotonin as measured off, uh, th- through the nose? Like, like, for instance, if you see a fluctuation in dopamine through one of these nasal probes-

    16. RMDr. Read Montague1:35:43

        The, okay, what we see, uh, in the nasal recordings looks very much i- like exactly what we would expect if we were recording from the neurons in the midbrain, based on what people have recorded on the simple experiments. You know, there’s a cue-

    17. AHAndrew Huberman1:36:00

        Mm-hmm

    18. RMDr. Read Montague1:36:00

        ... there’s a reward, there’s this, it went up, it went down, that kind of thing. There, this is a positive picture. This is a negative picture. This is positive affect. This is negative affect.

    19. AHAndrew Huberman1:36:09

        Okay, so d- dopamine increases when there’s a positive expectation.

    20. RMDr. Read Montague1:36:13

        Uh-huh.

    21. AHAndrew Huberman1:36:13

        Serotonin increases when there’s a negative expectation.

19. 1:36:16 – 1:45:14

    Sleep; Divorce; Science is a Contact Sport

    1. RMDr. Read Montague1:36:16

       Yes.

    2. AHAndrew Huberman1:36:16

       And you’re recording that from the nose, essentially noninvasively, except some- somebody has to put a wire-

    3. RMDr. Read Montague1:36:20

       Uh, apparently, the-

    4. AHAndrew Huberman1:36:22

       ... pseudoinvasively

    5. RMDr. Read Montague1:36:22

       ... language is minimally invasive.

    6. AHAndrew Huberman1:36:24

       All right, well, cool. I’ll, I can live with minimally invasive.

    7. RMDr. Read Montague1:36:28

       So I haven’t done it yet myself-

    8. AHAndrew Huberman1:36:29

       Mm-hmm

    9. RMDr. Read Montague1:36:29

       ... because when I, when I, when I was scheduled to do it, we realized we, uh, clipped the age at sixty-five, and I had had a birthday on Sunday, and I aged out, so I’m-

    10. AHAndrew Huberman1:36:39

        You’re... How old are you now?

    11. RMDr. Read Montague1:36:40

        I’m sixty-six.

    12. AHAndrew Huberman1:36:42

        You’re looking good, man.

    13. RMDr. Read Montague1:36:43

        Well. [chuckles]

    14. AHAndrew Huberman1:36:43

        People are gonna be like: What are your, what are your protocols?

    15. RMDr. Read Montague1:36:45

        [chuckles]

    16. AHAndrew Huberman1:36:46

        You know, raise five kids, run a big lab.

    17. RMDr. Read Montague1:36:48

        Right. So never sleep.

    18. AHAndrew Huberman1:36:49

        Never sl- do you not sleep?

    19. RMDr. Read Montague1:36:50

        Never sleep. Not really.

    20. AHAndrew Huberman1:36:51

        Do you not sleep well, or you just work all the time?

    21. RMDr. Read Montague1:36:54

        You know, my dad, who died at ninety-one in 2021, uh, he, he didn’t sleep.

    22. AHAndrew Huberman1:37:00

        Well, take that, Matt Walker-

    23. RMDr. Read Montague1:37:01

        He-

    24. AHAndrew Huberman1:37:01

        ... Brian Johnson.

    25. RMDr. Read Montague1:37:02

        He-

    26. AHAndrew Huberman1:37:02

        You don’t have to sleep to live to ninety-one.

    27. RMDr. Read Montague1:37:03

        Well, it may be that-

    28. AHAndrew Huberman1:37:04

        There are a lot of that’s genetics, too.

    29. RMDr. Read Montague1:37:05

        It’s a set.

    30. AHAndrew Huberman1:37:06

        Yeah.
20. 1:45:14 – 1:54:14

    Long-Term Motivation, Learning How to Fail, Tool: Kids & Sports

    1. AHAndrew Huberman1:45:14

       public-facing person. [laughing] But science made, made all of this feel much easier.

    2. RMDr. Read Montague1:45:20

       Oh.

    3. AHAndrew Huberman1:45:20

       Like, there's... Much easier. I mean, it's different, right? But science, I mean, I don't wanna get into war stories about long hours 'cause no one's interested in that, but yeah, science is a thorough ass-kicking with the occasional reward.

    4. RMDr. Read Montague1:45:32

       Plus, it's biology.

    5. AHAndrew Huberman1:45:33

       Plus, it-

    6. RMDr. Read Montague1:45:33

       Meaning, even when you're right on Tuesday-

    7. AHAndrew Huberman1:45:35

       Sure

    8. RMDr. Read Montague1:45:36

       ... eventually, it's like, "Oh, well."

    9. AHAndrew Huberman1:45:38

       Totally. Uh, but this gets us back to dopamine and rewards, which is one thing I will say is very... I- in my experience, was very valuable about doing a PhD, um, about working in a lab, doing biology experiments, is that it teaches you to set up a reward, expectation, motivation, contingency loop that is based on everyday things and long-term goals. I mean, I think one of the features of being a healthy human is being able to like, "Oh," like, "Hey, you know, it was a great cup of coffee this afternoon," but also, um, register the serotonergic, like, "Ah, that experiment failed again." But then, when things are working again, you can kind of feel, like, get some motivation from that and not just think about the PhD as the reward, right? So I go through life now not expecting great things to happen every day or even every week because I was trained in a system where the big rewards came every couple of years in terms of publishing papers, sometimes more frequently-

    10. RMDr. Read Montague1:46:40

        Mm

    11. AHAndrew Huberman1:46:41

        ... but, you know-

    12. RMDr. Read Montague1:46:41

        Mm

    13. AHAndrew Huberman1:46:41

        ... it's a long-term thing. But what about for the more typical example in people, where, you know, you grow up and things are either really easy, really hard, or for most people, it's kind of a mix. Do you think that that's part of us learning how to navigate life going forward? Like, you gotta register your wins in order to continue to have motivation. Um, you also need to register your losses-

    14. RMDr. Read Montague1:47:04

        You have to sustain your-

    15. AHAndrew Huberman1:47:04

        ... in order to not make the same stupid mistakes.

    16. RMDr. Read Montague1:47:07

        You have to sustain your losses, right, and get up again. Um, th- this is why I like sports for kids, okay? So I've made all my kids do sports, and one of them did competitive dance.

    17. AHAndrew Huberman1:47:18

        So sports as a means to-

    18. RMDr. Read Montague1:47:19

        It-

    19. AHAndrew Huberman1:47:19

        ... understand effort, reward, contingency over time.

    20. RMDr. Read Montague1:47:21

        And learning how to lose-

    21. AHAndrew Huberman1:47:23

        Mm-hmm

    22. RMDr. Read Montague1:47:24

        ... even though you've brought everything you could do that day, the best you could possibly do. Yeah, somebody's better than you. You know, what are you gonna do now? You know, that, that is a template for a lot of lessons. Um, same thing for students in science labs, especially mine. Students do things, they come, they show me something, and I go, "Pshew!" You know, and then they feel sad [chuckles] and... But I watch them evolve. They evolve. You know, they all, they all get better at it, and then they do this transition. You know, graduate students, I mean, maybe this is a little academic, graduate students are completely worthless to you for a long time, and then-

    23. AHAndrew Huberman1:48:07

        Not in my experience-

    24. RMDr. Read Montague1:48:07

        Well, in my, in my, in my world-

    25. AHAndrew Huberman1:48:09

        Yeah

    26. RMDr. Read Montague1:48:09

        ... they have so much to learn before-

    27. AHAndrew Huberman1:48:11

        Well

    28. RMDr. Read Montague1:48:11

        ... they can do anything. That's what I mean. No, I mean, as people, they're valuable. They're there. You're, they're your grad, your-

    29. AHAndrew Huberman1:48:16

        You mean in terms of data output? Yeah, well, they don't-

    30. RMDr. Read Montague1:48:18

        Yeah
21. 1:54:14 – 1:55:34

    Sponsor: LMNT

    1. RMDr. Read Montague1:54:14

       unmanageable, but, you know, they're all out there, and they compete at the level they can compete at, and they win and lose, and it's just a great le- I can't teach a kid a, a lesson that good.

    2. AHAndrew Huberman1:54:24

       Mm-hmm.

    3. RMDr. Read Montague1:54:24

       So, and that's training these same systems. It is. Expectations, disappointment, elation, recovery, do it again. It's all built in. I'd like to take a quick break and acknowledge one of our sponsors, LMNT. LMNT is an electrolyte drink that has everything you need and nothing you don't. That means the electrolytes, sodium, magnesium, and potassium, all in the correct ratios, but no sugar. Proper hydration is critical for brain and body function. Even a slight degree of dehydration can diminish your cognitive and physical performance. It's also important that you get adequate electrolytes. The electrolytes, sodium, magnesium, and potassium, are vital for the functioning of all cells in your body, especially your neurons or your nerve cells. Drinking LMNT makes it very easy to ensure that you're getting adequate hydration and adequate electrolytes. My days tend to start really fast, [chuckles] meaning I have to jump right into work or right into exercise, so to make sure that I'm hydrated and I have sufficient electrolytes, when I first wake up in the morning, I drink 16 to 32 ounces of water with an LMNT packet dissolved in it. I also drink LMNT dissolved in water during any kind of physical exercise

22. 1:55:34 – 2:04:38

    Meditation, Breathing, Learning; Dopamine as a Currency

    1. RMDr. Read Montague1:55:34

       that I'm doing, especially on hot days when I'm sweating a lot and losing water and electrolytes. LMNT has a bunch of great-tasting flavors. In fact, I love them all. I love the watermelon, the raspberry, the citrus, and I really love the lemonade flavor. So if you'd like to try LMNT, you can go to drinklmnt.com/huberman to claim a free LMNT sample pack with any purchase. Again, that's drinklmnt.com/huberman to claim a free sample pack.

    2. AHAndrew Huberman1:55:59

       I'm gonna come back to your athletic career, but I want to, uh, ask about meditation and breathing. Um, I think of meditation as some variant on close your eyes, focus on your internal state.... direct your attention to your breathing or the, your forehead. I know there are walking meditations, open monitoring meditations, but I think most laboratory and most people, when they think meditating, they're doing something like what I just described.

    3. RMDr. Read Montague1:56:23

       Mm-hmm.

    4. AHAndrew Huberman1:56:23

       And I think of it as a perceptual exercise first, like you're deliberately setting your perception internally, not externally. Uh, I understand there's these insights into consciousness, improved sleep, reduced stress, but that's all secondary and tertiary to me. What is the consequence of going into, of the, doing the practice of meditation, directing your state inward as opposed to outward, eyes closed, focusing inward, breathing in a controlled way? What does that do to dopamine and serotonin, and/or what are dopamine and serotonin just doing when you go from, like, a conversation that we're having to a meditation?

    5. RMDr. Read Montague1:57:02

       So we've been doing experiments on this with my graduate student, Nishka Raheja, who, um, went to The Ohio State University, and then worked in, um, [lips smack] a guy called Jeff Schoenbaum's lab at the intramural program in Baltimore. This is NIDA, National Institute of Drug Abuse. Um, came highly recommended to me, and so she wants to study the neural basis of mindfulness meditation. She's herself a meditator. Um, there's a whole bunch of narrative that you put on top of this thing, and I'm a little bit of a feet on the ground, real simple mind, simple. So I said, "I'll do that, but we're gonna do all these breathing experiments first." And so she's been, um, in two settings. One is recording f- from the amygdala, the anterior cingulate cortex, or the hippocampus, while people are doing structured breathing. This is her instructing them to breath, you know, inhale, one, two, three, four, hold, exhale, okay. I sit here, and I'm not instructed to do anything.

    6. AHAndrew Huberman1:58:01

       Mm-hmm.

    7. RMDr. Read Montague1:58:02

       I'm just breathing.

    8. AHAndrew Huberman1:58:03

       Just free form.

    9. RMDr. Read Montague1:58:03

       Free form breathing. So, um, well, it cycles with it. Norepinephrine and dopamine cycle with the breathing cycle. The most interesting-

    10. AHAndrew Huberman1:58:13

        On inhale, exhale, or overall, they change as you do this?

    11. RMDr. Read Montague1:58:16

        Well, I, that kind of granular detail-

    12. AHAndrew Huberman1:58:17

        Yeah

    13. RMDr. Read Montague1:58:18

        ... is waiting on-

    14. AHAndrew Huberman1:58:19

        Okay

    15. RMDr. Read Montague1:58:19

        ... numbers.

    16. AHAndrew Huberman1:58:20

        Okay.

    17. RMDr. Read Montague1:58:20

        Uh, but I can, the, the general gist now, this is from deep structures in the brain, is that, um, [lips smack] easy breathing, you can just see the co- you can, it, it, it is like a metronome. The amplitude of the neurotransmitter fluctuations follows the inhale, exhale cycles.

    18. AHAndrew Huberman1:58:41

        Wow!

    19. RMDr. Read Montague1:58:41

        It's right with it. It's very easy. You feel like you're watching the brain stem work.

    20. AHAndrew Huberman1:58:46

        Okay.

    21. RMDr. Read Montague1:58:46

        So when I tell you-

    22. AHAndrew Huberman1:58:47

        Mm-hmm

    23. RMDr. Read Montague1:58:49

        ... breathe in, two, three, four, hold, you know, da, da, and now exhale, okay. All hell doesn't break loose, but it becomes hard for them to follow, and the transmitters are kinda wiggling and wobbling, too. Okay, so that's in people that are in the epilepsy monitoring unit. Uh, this is taking place at Phoenix, at Banner Hospital, with our colleague, Robert Biiner. The most exciting stuff is using this probe that we can put up the nose of healthy people, uh, and do the same sort of thing, and we see generally the same sort of thing. The, the whole instructed breathing, you have to engage cognitive control over it, and you're, um, differentially adequate at doing that.

    24. AHAndrew Huberman1:59:33

        So they're, they're, they're doing structured breathing. Does dopamine track, uh, map onto the breathing?

    25. RMDr. Read Montague1:59:39

        Yes, but the interesting thing is, we have people playing, uh, an economic exchange game. It's called an ultimatum game. Ultimatum game should be labeled, "Take it or leave it." I have $20. I'm gonna offer you a split, eight to you, 12 to me, okay? Control passes to you. You're gonna either accept that, in which case, we walk away with eight for you and 12 for me, or you're gonna reject it, in which case, no one gets anything. What do people do? Well, you know, they tend to, they see the inequity across the players as a signal, and at about 80/20, you're indifferent. In other words, 80% to me, 20% offered to you, 50% of the time you're gonna say, "I'll take it," 50% of the time you're gonna send me a signal and say, you know, "Go home. I'm not taking that money." So nobody gets anything at a cost to you.

    26. AHAndrew Huberman2:00:28

        Mm-hmm.

    27. RMDr. Read Montague2:00:28

        When you reject it, it's at a cost to you. The pattern that we see, recording up the nose, uh, is reg- the breathing is registered cleanly with the peroxide signal, which is a, which is a proxy for mitochondrial function, and the dopamine signal, and the norepi signal. So the norepi- as, as this pattern of exchange is going on between the two of us, if you're gonna update a model, in other words, if the signal across the two of us is such that you have to do some learning, it's like your breath, your maximum breathing is tracking when you're gonna need oxygen in the mitochondria to produce ATP, to make an update that's gonna be, um, [lips smack] allowed by the dopamine signal. It's the most amazing looking data I've ever seen, and this is... In other words, your breathing and your dopamine signal in your nasal epithelium seems registered, depending on the demands of the task and the elements of the task.

    28. AHAndrew Huberman2:01:29

        Is this why you refer to dopamine as a currency?

    29. RMDr. Read Montague2:01:33

        Yes. I refer to it as a currency mainly for the reason that a currency is used. It's a way to take dissimilar objects and assign a common value scheme to them. Like, if I were gonna trade cups for windshields-

    30. AHAndrew Huberman2:01:46

        Mm-hmm
23. 2:04:38 – 2:13:18

    Function of Sleep, Motivation; Time Perception & Dopamine, Tracking Time

    1. AHAndrew Huberman2:04:38

       Mm-hmm

    2. RMDr. Read Montague2:04:38

       ... to make chips that run and do the same computing but on 40% of the power. I mean, server centers are amazingly, and just our computing machinery is amazingly inefficient, and so there's great things to come-

    3. AHAndrew Huberman2:04:53

       Mm-hmm

    4. RMDr. Read Montague2:04:53

       ... as people take on this problem. But w- we don't understand how it is that we get away to run our entire brain on 23 watts.

    5. AHAndrew Huberman2:05:03

       Well, earlier, when we were talking about sleep, and we talked about meditation, um, I wanna make sure that, um, [lips smack] I at least offer you the opportunity to speculate, what do you think the, um, kind of rejuvenative properties of sleep and meditation, um, are, uh, you know, for instance, if, uh, however little you need to sleep, if you don't sleep for two days, you are a different beast altogether. And sure, adenosine goes up, and the inflammatory markers go up. Uh, there are a lot of reasons for that, but motivation goes way down. Dopamine dynamics change completely, right? Um, [lips smack] so w- what do you think allows us to replenish this currency, uh, you know, in sleep? Like, what is it? Is it the slow breathing in meditation and sleep that allows-

    6. RMDr. Read Montague2:05:54

       You probably- it's a combination of physiological responses and the algorithmic cleaning up. It's a com- it's a computational device. At least we see it as a computational device. That's the modern metaphor for how we go in and un- understand it, and it has to erase stuff. You need a time off. You don't need in- you can't have information streams processing through when you need to be going, "Oh, I don't, not, I'm not gonna save all that, or I'm gonna consolidate that-

    7. AHAndrew Huberman2:06:21

       Mm-hmm

    8. RMDr. Read Montague2:06:21

       ... and I'm" a lot of it's about erasure and homeostasis and recovery. I mean, that translates physically into recycling transmitters-

    9. AHAndrew Huberman2:06:29

       Mm-hmm

    10. RMDr. Read Montague2:06:29

        ... and rebuilding all that, and-

    11. AHAndrew Huberman2:06:32

        'Cause there's nothing like the kind of motivation we feel after a great night's sleep, the way we interpret events and-

    12. RMDr. Read Montague2:06:37

        And all animals sleep. It used to be thought the echidna didn't have REM sleep, but that's no longer... That's false.

    13. AHAndrew Huberman2:06:43

        It's the first time the echidna's been mentioned on this podcast.

    14. RMDr. Read Montague2:06:45

        Okay, there we go.

    15. AHAndrew Huberman2:06:46

        You may not want to g- go here, so feel free to say pass, but I'm very, um, interested in the relationship between dopamine and other neuromodulators and time perception.

    16. RMDr. Read Montague2:06:55

        Ah.

    17. AHAndrew Huberman2:06:56

        Could we start with some, a general exploration of this? So really, like, in the simplest way, if dopamine levels are artificially increased with a drug, what happens to time perception?

    18. RMDr. Read Montague2:07:06

        It changes. [laughing]

    19. AHAndrew Huberman2:07:08

        [laughing]

    20. RMDr. Read Montague2:07:09

        Uh, one of the things that's latent in any description, um, of what dopamine is doing, either from a point of view of psychology or, uh, algorithms that I focus on, um, is timing. Okay, so you, to, to learn something is to suppress the statement. You learn something about what's going to happen w- when and how much.

    21. AHAndrew Huberman2:07:31

        Mm-hmm.

    22. RMDr. Read Montague2:07:31

        You know, what, where, when, and how, and so you have to have a lot of clocks in there.

    23. AHAndrew Huberman2:07:36

        Mm-hmm.

    24. RMDr. Read Montague2:07:37

        Okay? It us- as, as you well know, it used to be thought we had this one area, the suprachiasmatic nucleus, it set daylight cycles, et cetera, and all, and that was one of the main sources of clocks. Now, what we know is every cell in your body has clocks in it, and many, multiple clocks. Um, this is true for using these dopamine signals, too. You not only have to have clocks, you have to be able to register the time that something was happening. Now, I don't know exactly how that's done, but we just know that the system learns particular times and whatnot, and so, um, those almost certainly have to be rejuvenated and reset. There's a whole literature in rodents called the interval timing literature-

    25. AHAndrew Huberman2:08:19

        Mm-hmm

    26. RMDr. Read Montague2:08:19

        ... where you teach an animal to anticipate something at a particular time in the future, in the near, near future-

    27. AHAndrew Huberman2:08:24

        Mm-hmm

    28. RMDr. Read Montague2:08:24

        ... a few seconds. Um, and dopamine plays a critical role in that, and there's a group in London whose, I forget the PI's name, um-... who uses that and uses manipulations in humans of dopamine, dopaminergic drugs, to look at time perception changes, but these are whole body. They're like, "What did you perceive?"

    29. AHAndrew Huberman2:08:45

        Mm-hmm. Is there a simple statement that we can make? Like, if we, if you increase dopamine pharmacologically, and then you, does your perception of time shift to it moving faster or, uh, slower?

    30. RMDr. Read Montague2:08:57

        No.
24. 2:13:18 – 2:18:33

    LLMs, AI, Uses & Problem Solving

    1. RMDr. Read Montague2:13:18

       than the things, uh, that our kids are embedded in. I, I think it's different. I'm not sure it's also pathological.

    2. AHAndrew Huberman2:13:26

       Mm-hmm.

    3. RMDr. Read Montague2:13:26

       The adults in the room all share a worry over it, but we don't know really what to do. I don't think we do. Um, and then, you know, these large language models, I don't know if, how much you talk to them, but, you know, they speak 180 languages.

    4. AHAndrew Huberman2:13:43

       I use Claude.

    5. RMDr. Read Montague2:13:44

       I love Claude.

    6. AHAndrew Huberman2:13:45

       I love Claude AI. I, uh, you know, I love the interface. I think the-

    7. RMDr. Read Montague2:13:49

       Yep

    8. AHAndrew Huberman2:13:49

       ... answers it- I use it for research from time to time.

    9. RMDr. Read Montague2:13:52

       Do you ask it to summarize areas for you?

    10. AHAndrew Huberman2:13:55

        I ask it to direct me to literatures. I guess I've asked it for some summaries here and there, but I've asked it to compare and contrast things, which is really cool, 'cause I can't do that in PubMed. I can't go into PubMed and say, "Compare and contrast Read Montague's, uh, picture of dopamine, uh, to someone else's," uh, but Claude can, um, do that. It can set up a five-person panel of, uh, around a topic in Claude. I use it, uh, more and more these days, and I love it. I also really like the interface. It's very clean, and I'm, I, I care about aesthetics, um, [lips smack] and I think it's awesome.

    11. RMDr. Read Montague2:14:30

        The game I've been in isn't the artificial intelligence end or, or even the neurobiology end. I've been at the interface-

    12. AHAndrew Huberman2:14:36

        Mm-hmm

    13. RMDr. Read Montague2:14:36

        ... of those two, so I've lived in a, a narrow space that shuttles-... stuff from one world into the other world? I, I, I mean, I've used, uh, algorithms to organize biological observations, basically. I'm the, I'm the middleman in a way.

    14. AHAndrew Huberman2:14:51

        Mm-hmm.

    15. RMDr. Read Montague2:14:52

        I never thought this neural network training would scale the way it has. I just, I would never have guessed the way it does, and I know there are the, you know, the, the dissenting voices-

    16. AHAndrew Huberman2:15:03

        The doomsday people.

    17. RMDr. Read Montague2:15:04

        Yeah, "It doesn't really do very well. It doesn't..." Well, I mean, compared to who? Does anyone know anyone else that can speak 170 languages, that can translate 170 languages? I, I don't know anyone that can translate accurately 170 languages.

    18. AHAndrew Huberman2:15:18

        What do you use it for, things like Claude? Just, uh, do you use it as a kind of a search engine, or?

    19. RMDr. Read Montague2:15:24

        Well, I ask it: What's the relationship between the subjunctive mood and the use of complex numbers in quan- in non-relativistic quantum mechanics? I asked it that recently.

    20. AHAndrew Huberman2:15:34

        Just for fun.

    21. RMDr. Read Montague2:15:35

        In quantum mechanics, at, at least not quantum field theory, but in quantum mechanics, uh, [lips smack] the ways things m- might happen c- influence the probability of the way they actually turn out, okay? Whether or not you traverse that, you have to add up all those possibilities, right? It's like a counterfactual. It's, it's like a, um, mathematical rendering of a counterfactual, but it's based on experiments people have done in the, the real world for 100 years. And the subjunctive mood in conditional is the same sort of thing. We discovered in lang- once we discovered how to speak language, we discovered how to make reference to the thing that would be if something else had happened. That they're sort of the same. I didn't say anything, but just: What's the relationship between that? And it wrote this beautiful little essay, as it were, and I just thought, "Okay, I, I, I don't really care whether it maps onto some notion of consciousness or smart or..." That's-- I don't know anybody that could do that. I don't know any person that could do that, and it's a better writer than I am. I mean, maybe that's me, but, um, I'm just blown away by it, and I'm even... I'm more blown away by the reinforcement learning guys, uh, the David Silvers and the Go groups and the AlphaFold, and, you know, they solved the protein folding problem. Uh, DeepMind, the company that was in- owned by Google and, uh, and so I guess Google won one, two, three, four... There were three Nobel Prizes or something this time. Well, I, the, the thing that happened that AlphaFol- AlphaFold is the program that takes DNA sequences and predicts protein structure, and this is what Jumper and Hassabis got the Nobel Prize for. You know, that's a problem that the NIH has probably spent $100 billion on for the last 70 years, okay? They've also spent money on people crystallizing proteins and seeing where the atoms are and whatnot, and what they showed is they can develop a mapping between the sequence and the predicted protein structure, which is just... I mean, it was, it was, it was stunning to me! Now, it required all that crystallography data, but, um, their general approach was treating it like a game, like they had treated Go, where you do this reinforcement learning thing, and you say, you take a long sequence of moves, and the game ends, and you get an outcome, win or lose, and that's enough to train up the best player that's ever existed in history. And then they used AlphaGo Zero to train up to be a grandmaster chess player. Uh, back a few years ago, it took 30 or 40 days, I, and I think they're down to, I mean, from scratch. So I mean, if anybody's gonna write a history book on that, those are, those are historical breakthroughs, really, and those algorithms are installed in our

25. 2:18:33 – 2:25:57

    Future Projects, Commercial Brain-Machine Interfaces; Concentration

    1. RMDr. Read Montague2:18:33

       heads. Biology discovered that this is the way to handle the reality, that w- whatever it is, given the constructs that are generated by our brains, and, and it keeps us alive. That's just the start, is what I think. In other words, the neural reinforcement learning world, um, is going to continue to grow. It's gonna explode. We're gonna really start to understand that, and we may even understand how to engineer it.

    2. AHAndrew Huberman2:18:57

       Let's say somebody wants to get better at understanding where they're at in the whole learning, motivation, reward, contingency, dopamine thing. They're not gonna drop a wire into their brain. They may or may not be able to participate in one of these experiments, but let's say somebody wants to kind of just, uh, reflect on their, on where they are strong and where they are weak at the level of the algorithms they're running.

    3. RMDr. Read Montague2:19:23

       Ah.

    4. AHAndrew Huberman2:19:23

       I'm not suggesting you necessarily have anything for them right now, but aside from telling them to go play a competitive sport-

    5. RMDr. Read Montague2:19:30

       I have a postdoc that's making a company that's going to commercialize these things up people's noses, um, when it goes from skunk work to kinder and gentler, um, and you could, you could hack your own serotonin onto your cell phone. You could put it up there, and you could go do a thing, and you could watch it on your cell phone, and, um, we've never had anything like that before. Like, I wonder what happens when I do this. I know I feel... You know, what happens when I solve a Scrabble puzzle, or what happens when I... Uh, you can do it yourself. That's, that's his goal, is to take this company and put it into a commercial space where people could make personal use of it.

    6. AHAndrew Huberman2:20:15

       Oh, my God, I can give this to this person who's asking me about their dating life, and they can, uh, figure out how their dopamine reward expectation contingencies-

    7. RMDr. Read Montague2:20:22

       Well-

    8. AHAndrew Huberman2:20:22

       -are running them

    9. RMDr. Read Montague2:20:23

       ... it would be, it would be very interesting-

    10. AHAndrew Huberman2:20:24

        Mm-hmm

    11. RMDr. Read Montague2:20:24

        ... to sit and run scenarios through your mind and run them through again and ask yourself, ask whether you saw something like that going on with the mono- the signaling that's available in your nose. That's the kind of experiments we're doing now. We have sentences playing out to people that have-... um, w- as each word occurs, there's a probability that there's gonna be a valence change in the sentence, and we're looking at how it tracks this word by word.

    12. AHAndrew Huberman2:20:51

        Mm-hmm.

    13. RMDr. Read Montague2:20:51

        We have people playing social exchange games, um, thinking about themselves and others. I can imagine, there's probably somebody out there that has even better ideas about how you could use it, right? I mean, I sit and work on the other end of it, but, um, so I'm hoping he, uh, that's gonna hit the big time for him.

    14. AHAndrew Huberman2:21:13

        Could you give me an example of something that you're particularly excited about that would make one of your kids' lives easier?

    15. RMDr. Read Montague2:21:20

        L- learning how to concentrate. Like, if I had a pr- like, this company, uh, this is Seth Batten. His company's called Nebula Neuro. He, um, if he had a probe that we could put up there easily, like the little squishy things in your ears, um, then you could give him that, and you could ask him to servo on their neurotransmitter release.

    16. AHAndrew Huberman2:21:41

        So they would read a passage. You're getting real-time readout-

    17. RMDr. Read Montague2:21:46

        Uh-huh

    18. AHAndrew Huberman2:21:46

        ... of dopamine and serotonin.

    19. RMDr. Read Montague2:21:48

        And then you make a suggestion about how to learn something about it, pay attention to a component of it, or you could do something as simple as lower this, lower this thing right here, lower this signal right here. We just haven't had a way to measure that in real humans, in, in, in, in settings that are like the real world. S- so you take 1,000 people, and you say, "Oh, look, these people are really comprehending in a way that we want them to comprehend, and these are in the middle, and these are, wow, they're way off beam here." And then you train a neural network who looks at their performance step by step with the transmitters there, and it generates a picture of that. That kind of thing is gonna dominate neurobiology coming up. I mean, it's changed, whether or not people realize it or not. So many people are getting trained in it over here, but these are the important problems. These are the human behavior, human mind, human perception problems. That's what you really want to get at, e- especially for mental illness and stuff like that. It's not gonna be one... It's not gonna be a simple one thing. So the fact that these neural networks have had a, a big breakthrough, and how do we train them and how do we-- and there's still a ton of stuff we don't know. These networks often learn things that the designers don't know they know.

    20. AHAndrew Huberman2:23:02

        And I think that scares a lot of people, but I think there's excitement in it, uh, to be had in it also.

    21. RMDr. Read Montague2:23:08

        And they're very convincing. They can make very convincing arguments and things like that, and so I just think letting it look at data, I, I, I can't imagine a neuroscience experiment, certainly on humans, where you wouldn't do that, where you wouldn't shine these networks on that and feed them the data. So a lot of this is gonna be, how do you collect the data? How do you feed it to the n- networks and whatnot? So I'm very excited about that. I'm, I'm excited about it because it was made fun of so much 30 years ago. "Oh, reinforcement learning can't learn anything."

    22. AHAndrew Huberman2:23:36

        Everything in science was made fun of when... Now, these really sound like old, two old guys talking about it, but when I first started going to the ner- annual neuroscience meeting, two things were the dregs, like, no one attended those very few posters, which were AI and brain machine interface.

    23. RMDr. Read Montague2:23:53

        Ah.

    24. AHAndrew Huberman2:23:54

        Those were considered, like, the, like, really just, like, the, the bottom-of-the-pile stuff.

    25. RMDr. Read Montague2:23:58

        Now it's the hot thing.

    26. AHAndrew Huberman2:23:59

        Yeah.

    27. RMDr. Read Montague2:24:00

        Right.

    28. AHAndrew Huberman2:24:00

        And for a while there was the, you know, molecular tools and genetic tools, and those are still awesome, but now AI and, and brain, brain-machine interface-

    29. RMDr. Read Montague2:24:08

        Yeah

    30. AHAndrew Huberman2:24:08

        ... is, like, the all the rage.
26. 2:25:57 – 2:30:17

    Dopamine “Hits”?; Depression & Schizophrenia; Quitting

    1. AHAndrew Huberman2:25:57

       We've talked a lot about social media and reward contingencies and dopamine and stuff, but I also think that the human brain is adapted to conditions over and over and over again. So this younger generation that we're like, "How could you spend all this time on your phone?" We don't want them to destroy themselves. On the other hand, they're doing pretty well. Like, there, there are, there are examples of them doing spectacularly well, um, scrolling super fast and doing homework, playing sports, living their lives.

    2. RMDr. Read Montague2:26:19

       Mm-hmm.

    3. AHAndrew Huberman2:26:19

       So, um, you willing to answer some questions from the general public?

    4. RMDr. Read Montague2:26:23

       Sure, sure. Yeah.

    5. AHAndrew Huberman2:26:25

       Some great questions here. Um, some of them you've already answered, uh, but here's one I think is worth asking: How much of what the public hears about, quote, unquote, "dopamine hits" is neuroscience BS, meaning it's probably not real neuroscience, and how much has an evidence base when we hear this thing, dopamine hits?

    6. RMDr. Read Montague2:26:45

       Something unexpected and rewarding-

    7. AHAndrew Huberman2:26:47

       Mm-hmm

    8. RMDr. Read Montague2:26:48

       ... causes a dopamine fluctuation, and that's true.

    9. AHAndrew Huberman2:26:51

       ... Okay, but it's an incomplete story. Do you think it's an oversimplification to assign a serotonin hypothesis of depression and a dopamine hypothesis of schizophrenia? And if so, what other points would you add?

    10. RMDr. Read Montague2:27:07

        It's a bit of a loaded question in that both of those chemicals are fluctuating in both of those disorders.

    11. AHAndrew Huberman2:27:14

        So involved, but that's not the complete story.

    12. RMDr. Read Montague2:27:16

        You know, it was the most conspicuous feature of schizophrenia, is the fact that blocking dopamine receptors turns the symptoms down a little bit. We discovered that a long time ago. It was, it was very early on seen as a hyperdopaminergic state, and it is that. I mean, it is that. If you block dopamine receptors, you don't hear voices anymore. If you take, uh, L-DOPA, and you don't have Parkinson's, and you don't have schizophrenia, I can find a dose where you will start to hear voices. I, I can find a dose where you will start to feel paranoid. I can make you schizophreniform, and so that's ration-- that's a rational assignment of dopamine, the, the, the features of schizophrenia. Schizophrenia is pretty ill-defined, and I think all these words are gonna start getting teased apart now that we can record things in healthy people, that we can record things in sick people, and we-- that we're recording these transmitters in people that have these actual disorders.

    13. AHAndrew Huberman2:28:13

        This person is curious about the serotonin-to-dopamine ratio in quitting decisions. At what point does the neurochemical drive to persist, what they're thinking of as dopamine pursuit, become pathological against the valuation signal that says, "This isn't working"? In other words, what's the line between grit and su- sunk cost fallacy? They, they want a lot answered in this one.

    14. RMDr. Read Montague2:28:40

        That's a great question. I think it leaves out something that we really don't know much about, which is some-- for these thing, these neurotransmitters to be released more or less, you have to set expectations. We know very little about how expectations for now are being set, the next ex-- and being updated from state to state to state, and that controls the fluctuations as much as anything. And so the representations in your brain of how they're held or gotten from memory, how they control brain states and stuff, that's not understood very well at all. That's what AI is gonna help us do in the next twenty years.

    15. AHAndrew Huberman2:29:23

        I love that. I, I really appreciate your answer, and guess what? Grok AI jumped in and answered as well, so we can see what Grok said. Um-

    16. RMDr. Read Montague2:29:30

        It answered what, that question?

    17. AHAndrew Huberman2:29:31

        That same que- yeah, so these people are asking questions on X.

    18. RMDr. Read Montague2:29:34

        So he has Grok running over all the-

    19. AHAndrew Huberman2:29:35

        Grok just jumped in and answered. This person didn't say... Oh, no, sorry, they tagged Grok, so Grok jumped in and answered.

    20. RMDr. Read Montague2:29:42

        I see, right.

    21. AHAndrew Huberman2:29:42

        If you ask a question on X and you tag Grok, so I'll tell you what Gr-

    22. RMDr. Read Montague2:29:46

        What did it say?

    23. AHAndrew Huberman2:29:46

        Grok said: "Great question! [chuckles] Research shows that dopamine drives persistence, grit, by reinforcing effort and reward anticipation. But high levels can trap us in sunk cost fallacies, ignoring when to quit. Serotonin helps balance by signaling outcome valuation. Low ratios may tip toward unhealthy persistence. Studies," and they cite a study, "link dopamine surges to overvaluing sunk efforts. Worth exploring with the expert!" Big, big exclamation mark.

27. 2:30:17 – 2:35:58

    Dopamine & Serotonin Misunderstandings; Internal Satisfaction; Motivation

    1. AHAndrew Huberman2:30:17

       [chuckles] You. [laughing]

    2. RMDr. Read Montague2:30:19

       That's funny.

    3. AHAndrew Huberman2:30:19

       Wild, right?

    4. RMDr. Read Montague2:30:20

       Yeah.

    5. AHAndrew Huberman2:30:21

       Did, did, how did Grok do?

    6. RMDr. Read Montague2:30:23

       Grok did well, if the brain is only a chemical machine. Grok left off the fact that it's an electrochemical machine, and that the electrical activity in the networks set things like expectations, which defines when the release is happening or not, and so, uh, um, that's half the book.

    7. AHAndrew Huberman2:30:42

       What's the one thing about dopamine the public seems to always misunderstand?

    8. RMDr. Read Montague2:30:47

       Dopamine equals pleasure.

    9. AHAndrew Huberman2:30:50

       Is not true.

    10. RMDr. Read Montague2:30:51

        Is not true.

    11. AHAndrew Huberman2:30:52

        Yeah. What's the one thing about serotonin the public always seems to misunderstand?

    12. RMDr. Read Montague2:30:56

        You know, I take drugs to increase my serotonin when I'm depressed. What they don't understand is that, um, those drugs are really heterogeneous, often pathological, and, you know, across decades, toxic. Um, so it's an unfortunate-- we're in an unfortunate moment there to reconfigure those, that kind of treatment. I bet you, uh, 'cause, 'cause I know people who swear by SSRIs. I mean, just it transformed their life, and they don't-- the side effects are nominal. Um, it'd be great to be able to identify them ahead of time, the candidates for whom that would work. You know, a lot of this is a placebo effect. Psychotropic meds, when you have a good outcome variable, fifty to eighty percent is a placebo effect, meaning not explained by any-- you can't explain the variance by anything, but...

    13. AHAndrew Huberman2:31:50

        Hmm.

    14. RMDr. Read Montague2:31:51

        But that doesn't mean it's a fake effect. Your expectations are set by that. Um, like, if you believe something is gonna happen, we, we have very poor understanding of really how your belief that something's happening in your brain actually marshals it.

    15. AHAndrew Huberman2:32:08

        This question, I am tempted to relate to meditation, but let's see what you say. Um, how do dopamine responses change when you remove external rewards and rely purely on internal satisfaction? Like, so I think of an example like meditation, like, where you're not, maybe you're not telling people, "I'm meditating," to get praise, but just going into a state or maybe drawing 'cause you like drawing, you're never gonna show your drawings, or what-- is there any idea of what happens when the, the reward-

    16. RMDr. Read Montague2:32:41

        No, there's not, but it would be fantastic to measure that. That's a fantastic question. To what degree can you, when cut off from the world, let's say in a sensory deprivation tank-... generate internal states that you chase and generate dopamine signals in that context. That's why I mentioned these not yet published measurement schemes.

    17. AHAndrew Huberman2:33:02

        Well, I'm telling, um, Oliver from the UK, "No info," but he said, "Yours is a superb question." Um, and guess what? That's a lot of external validation. Um, so it [clears throat] kind of runs countercurrent to the question, but right on, Oliver. I don't know you, Oliver, but, oh, it's interesting, many people are asking that same question: What has a greater influence on dopamine levels, exogenous or, um, it stim- uh, you know, feedback or our psychological framework? People are thinking about this a lot.

    18. RMDr. Read Montague2:33:32

        Well, they're linked.

    19. AHAndrew Huberman2:33:33

        Mm-hmm.

    20. RMDr. Read Montague2:33:33

        They're, they're, uh, uh, a little bit, uh... My simple answer, um, betrayed itself in a way. They're linked. Your, your ability to generate a clear expectation and hold it in mind, um, conscious- uh, uh, I, I guess we're talking about consciously here, right? Um, it's not really clear how good you are at that.

    21. AHAndrew Huberman2:33:58

        There are a lot of questions asking about how to, uh, create a, a capacity for persistent motivation-

    22. RMDr. Read Montague2:34:08

        Ah

    23. AHAndrew Huberman2:34:08

        ... um, under conditions where things aren't going well. You talked earlier about running up a hill and puking as a self-training, um-

    24. RMDr. Read Montague2:34:15

        Friday nights after the football game-

    25. AHAndrew Huberman2:34:18

        On Fridays.

    26. RMDr. Read Montague2:34:19

        I, I just did it because I could.

    27. AHAndrew Huberman2:34:21

        Till you actually vomited?

    28. RMDr. Read Montague2:34:22

        Oh, yeah. I mean, I don't know, snot and vomit-

    29. AHAndrew Huberman2:34:24

        Yeah

    30. RMDr. Read Montague2:34:24

        ... but it was, I, I was just-
28. 2:35:58 – 2:38:31

    Serotonin Syndrome; Acknowledgements

    1. RMDr. Read Montague2:35:58

       Shaved head?

    2. AHAndrew Huberman2:35:58

       Face, yeah. Yep.

    3. RMDr. Read Montague2:35:59

       He wore dark shades-

    4. AHAndrew Huberman2:36:00

       Yeah, yeah

    5. RMDr. Read Montague2:36:00

       ... and a giant gold chain around his thing.

    6. AHAndrew Huberman2:36:03

       So cool. Yeah, I mean, the, the high-intensity work that Arthur Jones, uh, encouraged, I think, is the best way to stimulate hypertrophy and what not, the super setting and-

    7. RMDr. Read Montague2:36:12

       Oh, I'm sorry.

    8. AHAndrew Huberman2:36:13

       Yeah.

    9. RMDr. Read Montague2:36:13

       You had to carry a bucket there-

    10. AHAndrew Huberman2:36:14

        Oh

    11. RMDr. Read Montague2:36:14

        ... because people would throw up so much.

    12. AHAndrew Huberman2:36:16

        Mm. Yeah, uh, high rep, high intensity leg day, you, you can definitely puke. Lot of questions about serotonin syndrome. I get questions about this all the time, people who feel like because of SSRIs, they are dealing with, uh, sexual side effects, anhedonia, motivational issues. What do you think the cause is?

    13. RMDr. Read Montague2:36:36

        Of all those things? It, it's the, those drugs are, are binding to all kinds of receptors, is what's happening, and there are all kinds of serotonin receptors. Okay? Un- y- you know, there's not that many different dopamine re- there are probably, what, 80 serotonin receptors or something? There's, there's a, there's a great, um, number of them, and so there's just a, a, a field of dreams of way you can sort of have side effects. Um, also, just the idea that you're on them-

    14. AHAndrew Huberman2:37:04

        Mm-hmm

    15. RMDr. Read Montague2:37:04

        ... is itself an effect.

    16. AHAndrew Huberman2:37:07

        Mm-hmm.

    17. RMDr. Read Montague2:37:07

        I'm on a drug. This is a drug to manipulate my mood state.

    18. AHAndrew Huberman2:37:10

        Mm-hmm.

    19. RMDr. Read Montague2:37:11

        That has an effect on your mood state and the way you feel.

    20. AHAndrew Huberman2:37:15

        Thank you for answering those questions. I, I, I wanna say a couple things. Um, first of all, thank you for taking time out of your very busy family, and work, and work out to puke, uh, often schedule. Um, despite the fact that you don't sleep much, um, you are very busy, and it's a really wonderful opportunity that so many people can learn about dopamine, and serotonin, and neuromodulator dynamics from somebody who really understands the science, past, present, and where it's going. Um, these are topics that many, many people hear about and think about, and it's super important that the conversation be up-to-date and nuanced, and you, you've done that for us today. I realize it's far from complete, so we'll have to have you back, but also, I just wanna say thanks for being, uh, the pioneer that you've been in forging a path that, at least to my knowledge, no one else in neuroscience is tackling all the technical challenges, thinking about the AI and the computational stuff, putting people into scanners, putting wires up people's nose, putting wires into people's brains. I... From the time I met you 15 years ago, um, it was very, very clear that you have a goal of solving the answers to particular

29. 2:38:31 – 2:41:24

    Zero-Cost Support, YouTube, Spotify & Apple Follow, Reviews & Feedback, Sponsors, Protocols Book, Social Media, Neural Network Newsletter

    1. AHAndrew Huberman2:38:31

       questions, and that you're gonna do whatever it takes to get those answers, and that's just awesome. Um, it's the spirit of science, uh, at its best, and, uh, we'll put links to your work, and I know you've written some things and given some other talks. Um, but I'm just so grateful. I learned a ton today, and I know everyone else has. So, um, you've done us all a tremendous service, so thank you.

    2. RMDr. Read Montague2:38:53

       Well, thanks for having me.

    3. AHAndrew Huberman2:38:54

       ... It's a blast. Thank you for joining me for today's discussion with Dr. Read Montague. To learn more about his work, please see the links in the show note captions. If you're learning from and/or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific zero-cost way to support us. In addition, please follow the podcast by clicking the Follow button on both Spotify and Apple. And on both Spotify and Apple, you can leave us up to a five-star review, and you can now leave us comments at both Spotify and Apple. Please also check out the sponsors mentioned at the beginning and throughout today's episode. That's the best way to support this podcast. If you have questions for me or comments about the podcast or guests or topics that you'd like me to consider for the Huberman Lab Podcast, please put those in the comments section on YouTube. I do read all the comments. For those of you that haven't heard, I have a new book coming out. It's my very first book. It's entitled Protocols: An Operating Manual for the Human Body. This is a book that I've been working on for more than five years, and that's based on more than 30 years of research and experience. And it covers protocols for everything from sleep to exercise to stress control, protocols related to focus and motivation, and of course, I provide the scientific substantiation for the protocols that are included. The book is now available by presale at protocolsbook.com. There you can find links to various vendors. You can pick the one that you like best. Again, the book is called Protocols: An Operating Manual for the Human Body. And if you're not already following me on social media, I am hubermanlab on all social media platforms. So that's Instagram, X, Threads, Facebook, and LinkedIn. And on all those platforms, I discuss science and science-related tools, some of which overlaps with the content of the Huberman Lab Podcast, but much of which is distinct from the information on the Huberman Lab Podcast. Again, it's hubermanlab on all social media platforms. And if you haven't already subscribed to our Neural Network Newsletter, the Neural Network Newsletter is a zero-cost monthly newsletter that includes podcast summaries, as well as what we call protocols in the form of one to three-page PDFs that cover everything from how to optimize your sleep, how to optimize dopamine, deliberate cold exposure. We have a foundational fitness protocol that covers cardiovascular training and resistance training. All of that is available completely zero cost. You simply go to hubermanlab.com, go to the Menu tab in the top right corner, scroll down to Newsletter, and enter your email. And I should emphasize that we do not share your email with anybody. Thank you once again for joining me for today's discussion with Dr. Read Montague. And last but certainly not least, thank you for your interest in science. [upbeat music]

Episode duration: 2:41:24