Speaker 0:00

Dopamine. You've probably heard of it. I've come across the trend of the dopamine detox. What you're doing is chasing the most refined dopamine loop that software has ever produced. Today we are going to talk all about dopamine. Porn addiction is very much about dopamine. Three natural ways to boost your baseline dopamine levels. And you see very little dopamine transmission. They are in a chronic dopamine deficit state. Dopamine. I know it's just dopamine. Dopamine. But it feels so real to me. Dopamine. I know it's just dopamine. But is it?

Ashley 0:37

I made that for you.

Cat 0:38

Was that you doing the Robyn cover?

Ashley 0:41

Cat 0:50

That was you secretly auto-tuning yesterday?

Ashley 0:53

Uh, yeah, you left for about an hour and I became Robyn

Cat 0:58

That's incredible. I'm so happy about this it seems like dopamine does a lot a lot to us, if not like sociologically, if not biologically.

Ashley 1:10

I just felt like, in, just in those clips alone, right? It's a good thing, it's a bad thing. You should fast, you should try to increase it. And like, what is the real story here? What should we actually know about dopamine? What is it actually doing in our brains? And like, how much do we actually know versus how much is this sort of like conversation about it and where we're just plugging in dopamine when we really mean something else?

Cat 1:33

Hmm. Yeah, my main impression about this whole thing is, I mean, my level of knowledge of this is, like, maybe a psychology 101 undergrad class where there was a box that said dopamine, and there was, like, an arrow that pointed to, like, reward. And that's my level, and you hear this phrase everywhere. I've certainly seen it everywhere in discussions about AI and coding, but I also saw it way before that. Like, I saw it with, discussions about should kids use social media? What is the internet doing to us? Like, kind of plug in the technology of the day, and there was a dopamine discussion for the last five years or something. So I'd love to hear your take.

Ashley 2:14

Dopamine is one of these scapegoats. Like, whenever we're upset about something, we're like, "Yeah, it's dopamine." Like, it's, it's smartphones, it's, like, AI, it's whatever you're upset about in society. Well, it's because we're fucking up our dopamine. And I feel like in so much of this conversation, dopamine has been wronged, you know? And like, and so in some ways, I'm here today in defense of dopamine. It's not a bad thing. It's actually a necessary thing. We're gonna talk about some of the things it does in your brain that are non-negotiable. Like, you need it. I'm sorry, but you can't dopamine fast. Like, you, you kinda need it. Um, and I think one really interesting thing to me is that even though dopamine right now in the current cultural zeitgeist is the villain, this actually hasn't always been the case. In preparing for this episode, I revisited this piece that I love by, um, computational neuroscientist Mark Humphries. He's over in the UK. He wrote this piece nine years ago called Crimes Against Dopamine. I send it to everybody anytime a conversation about dopamine comes up, basically. And I opened it up again, and the funniest thing is that in the intro to his piece, he's actually talking a little bit more about how dopamine at the time is framed as a positive thing. Like, it's something you should increase if you wanna get motivated. It's an explanation for why we love things, like why we love storytelling, for example.

Cat 3:36

Oh, like across society we were saying, "Wow, none of us have enough dopamine," at the time, and now we think we have too much

Ashley 3:42

Yeah, exactly. The conversation around it was, was totally different. And again, it's just because it's just become the thing that we point to, or one of the things we point to. So I wanted to talk a little bit today about like what is dopamine? What does it do? You said you had a psychology explanation of it. Is there anything else you kind of pull out of your like archives of psychology

Cat 4:04

Yeah, I'm gonna have to sit here and represent the person who truly doesn't know anything here. Um, this is just absolutely not a world that I know much about in terms of neurotransmitters, chemicals in the body. I'll sit here and be the audience. Like, I know we have chemicals in our body. I know that they get modulated by various things. Um, you know, maybe the biggest thing I feel familiar with is, like, antidepressants, right? So sometimes you end up not having enough of something. Um, I know about addiction. I know that there are biochemical, very, like, in your body physiological things that happen to people when they are addicted to things. Um, I know that that's scary. It's scary to imagine that you can get pulled into behaviors like that. Um, I wonder about things like the gut biome. I wonder about things like, uh, you know, we're increasingly talking about, oh, maybe your, your diet changes your s- I, I know a lot more about serotonin than I know about dopamine, so you know, serotonin's in your gut, right? There's a lot of

Ashley 5:10

Mm-hmm. So

Cat 5:11

confusing things out there. Yeah, well, see? There you go. Everything is everywhere, and I start, I start, I start, yeah, all at once, and I start to wonder about things like, um, do, does the stuff I do have a really targeted effect? Like, do some- does the food I eat impact the, the dopamine in my gut but not in my brain? Or what... You know, do they have to be at different levels? Are people right about this idea that you could get into, like, a deficit or a state that's bad where you're not getting the right feedback, you know? From the psychology point of view, I also know a lot about self-regulation, so I know about the kinda psychology level of this. It is hard for people to regulate. It is hard for people to kinda get out of bad habits. So what role does all of this play? That's a lot, but

Ashley 6:02

Yeah. No, that, that's a really good sort of set of questions, a really good sort of scan of the landscape. And I think, the challenging thing is to many of your questions, like for example, the question of, you know, if I play a video game for an hour, does it increase my gut dopamine or does it increase the dopamine in my, like, reward centers? And the answer to that is, like, we don't really entirely know, and as we're gonna get into a little bit later, it's actually really hard to study this directly in humans. It's extremely limited. You know, but generally speaking, yeah, dopamine, just like serotonin, is a neurotransmitter. These are signals, chemical signals that your brain uses to communicate. You've got it in multiple parts of your brain and your gut, as we just said. Um, so something I learned yesterday as I was doing some research for this is that you actually have dopamine in your eyeball. Um, it's helping regulating eye growth. Yeah. Yeah. So it's there. Um, another really big place where dopamine plays a role is in this set of brain structures called the basal ganglia. This is, a set of brain structures for movement, and this is the area of the brain where dopamine is impacted in Parkinson's disease.

Cat 7:11

What happens in Parkinson's disease?

Ashley 7:13

So in Parkinson's disease, a particular set of neurons in one brain region that release dopamine, um, degrade. They start to degenerate. We don't entirely know why. But yeah, so some of our treatments for Parkinson's, one of the mainline treatments is replacing dopamine, basically giving people either dopamine directly or precursors to dopamine to help increase the amount of dopamine in their brain. But then, you know, when people say dopamine, when we're talking about, like, dopamine hits or whatever, they're really talking about the dopamine in your midbrain, which is, like, the core of your brain. It's kind of the reward circuitry, the reinforcement learning circuitry. It's where we build habits, where we learn to do things through reinforcement or no reinforcement.

Cat 7:55

So dopamine hits are real

Ashley 7:58

Well, there's like a thing that's a dopamine hit, but it's not exactly what people mean when they say dopamine hit. And this is the thing that like if you talk to any neuroscientist who studies this stuff, it's the thing that like really rubs them the wrong way about all of this conversation, which is that people equate dopamine with reward, right? But really, dopamine is a reinforcement signal. It's not the this feels good signal, it's the I want more signal. And that's actually a big distinction

Cat 8:28

Um, can you unpack that a little bit for me? Aren't rewards the thing that reinforces you? Like what do you mean by that difference?

Ashley 8:34

Yeah, totally. So it's, it's subtle, right? But if we're gonna think about how the brain works and we're gonna try to understand how the brain works, we have to make this distinction. And so this brings us to, like, the classic study of dopamine. Everything that kicked off our understanding of reinforcement learning, all of the stuff about reinforcement learning and machine learning right now is based on this, 1997 study, by a group of people. They actually ultimately got a one million euro brain prize for this work. It's, like, really, really big deal. And what they did was they were recording from a monkey from those midbrain dopamine neurons that we were talking about, and they're doing, like, a classical conditioning experiment. So in a classical conditioning experiment, you're, like, pairing some tone or something with a reward. And they notice that when the monkeys get a reward that they are not expecting, there's this, like, little burst of dopamine in their brain. It's like, "Ooh!" Like, "What is that?" And I think this is, like, the thing that, you know, this... That was better than predicted. That's kind of the signal that those neurons are

Cat 9:41

Oh, so it's kind of like discovery. It's not like, "Oh, I expect this reward," which is maybe like the more compulsive behavior stuff. Like, "Oh, I expect this, and I want it, and I can't get out of it." You're more talking about like your brain wants to reward you. You go to a new bush and discover a new kind of berry you didn't know about, your brain really wants you to remember about that.

Ashley 10:04

Totally. It's like, "Oh, the bush has the berry. Like, how cool. Like, that was better than I expected."

Cat 10:10

But you go back to the bush, you already know about the berry, it's like a main food supply, you're not gonna get that same reward. Is

Ashley 10:16

When you go back to the berry... Yeah, this is, this is-- I love this example. So when you go back to the bush, those neurons don't fire when you get the berry. They actually fire at the sight of the bush. So this is the main finding of this paper, is that the signaling shifts. So initially, the signal is, "Wow, that was awesome, better than expected." And then the signal shifts to be more tied to the thing that triggered the reward, which in this case, in your example, is, like, the bush. So you see the bush and you're like, "Oh, there it is. I'm gonna go back and get it." So it's the signal that reinforces the behavior. It, it teaches you. It's a learning signal. It teaches you to go back to that thing that gave you a better than expected reward.

Cat 10:58

Hmm. So what does this change about, like, the way that people talk about it in social media or out there in the world? Like, what what's the misconception that you keep seeing?

Ashley 11:08

Well, I think it's just like a sloppy representation of what the brain does. Um, you know, I think like this particular point has less of a severe implication for the conversation about it because at the end of the day, what people are ultimately trying to do is they're just trying to like tie it to some brain circuitry. And, and in this case, they're just tying it to the wrong thing. So even though like dopamine ultimately as you learn things does start to get released as you feel good because it's this conditioning system, it's tied to it ultimately, the actual like signal in the brain that it is is just not that feel-good system. That's actually more of like opioids, for example. So it's kind of funny we don't say like, "Oh, I got an opioid hit." Like no one says like, "Oh, I got an endogenous opioid hit whenever whenever I like did this particular

Cat 11:58

yeah. Okay. Yeah. I'm already taking away the feeling of just kind of like this is a little bit more complicated than like thing happens, I get reward, now I'm trapped, and I can never get outside of that loop because, there's all sorts of other circuits ha- you know, being activated. And like one implication that I'm taking from it is if you see a study or a piece of evidence out there that says, "Look, you know, when people did X, like the dopamine increased," or, "When rats pushed a lever, the dopamine increased," that's really not telling you about everything that we experience in our day as we're like making choices about our own behaviors.

Ashley 12:37

It's like the worst case of biological reductionism where, like, you're, you're reducing this thing that is really complicated, you know. As you know, like, habit formation, as you mentioned earlier, self-regulation, there's all of these systems in the brain and the body that are here to, like, help us regulate our behaviors. It's not as simple... Like, we are, we are not as simple beings as, like, we do a thing and it feels good and we get reinforced for it, and then we keep doing it. Like, there's this endless cycle that is feeding back on that kind of behavior. Maybe one big takeaway is that this is a kind of negative, pessimistic view of what humans are like. We're not this, this simple feedback loop, you know? And, and you are also not subject to your own, quote-unquote, "dopamine," you know, or c- call it whatever molecule you want

Cat 13:25

So I have a question for you. Does this mean that you can engineer your dopamine because of the way that you think about the world and the way that you expect things? So like if you change your own expectations of, what you're gonna get Like I'm thinking about my world of, like expectancy value, you know, motivation cycles, and like if you change your expectation of what's gonna happen when you tackle a math problem and you say, "Oh, I'm gonna, I'm gonna actually see the friction as a good thing that's g- giving me a reward, that's telling me I'm working hard, and working hard is good, and I like that, and it's progressing me towards my goals." Like you can deeply change how aversive people find that experience and the meaning they take from it. So that's like the psychology level. Is it connecting to biology? Like is it changing the type of dopamine you're getting in the classroom, you know?

Ashley 14:15

Okay, so this is a really good question. I love that you asked this because I've been thinking a lot about expectancy effects for the book that I'm writing, actually. Because, you know, for example, when people get a placebo drug but they still get better, that's largely due to expectancy. They expected to get better, and so something must be happening in the brain when they expect to get better. And it's probably not mostly dopamine. Most of the research points to your internal opioid system. We call them the endogenous opioids. Uh, most research points to that being really important. Dopamine is almost definitely involved at some level because, as I mentioned earlier, it's the learning signal. It's the thing that's gonna ultimately reinforce the behavior. But expectancy itself probably manifests in the brain a little bit more with opioid signaling. That said, when we think about habit formation or even addiction, it is absolutely true that dopamine in the brain is changing. I mean, this is one of the biggest findings, and it's mostly people's background tonic dopamine levels. It ends up being that you need, a bigger hit in order to get that same feeling, in order to get that same reinforcement. So that is something, you know, that I think is worth thinking about, that maybe we have some lever of control over. It's not as simple as, oh, you shouldn't over-pleasure yourself because you're gonna, like, screw up your brain, right? That's kind of like "Dopamine Nation's" main point, right? And it's

Cat 15:55

a next question I have, which is like, how much does your body actually keep this in balance? And like when should you get worried about it? And how, how easily, how easy is it to knock this system off its homeostasis, you know?

Ashley 16:08

Yeah, and that's,

Cat 16:09

Are we all addicted to our phones, or is addiction the wrong metaphor?

Ashley 16:13

Addiction is like a very, you know, in, in the research, addiction has a very particular definition which people have debated over, right? In a simple version of it, it's a behavior that if you don't do, you go through withdrawal. So if you don't have withdrawal symptoms from your phone, then you're not addicted to it, at least by that one definition.

Cat 16:33

Ooh. Can you define, like what are withdrawal symptoms like actually?

Ashley 16:38

Yeah, withdrawal you could define either behaviorally or, biologically, right? You have, like, some negative response to not having the drug or not having the thing, right? So it's a hu- it's a hangover,

Cat 16:52

But I would say it, it's a very strong negative. It's a very strong threshold to meet because you-- it can't just be, "Oh, I miss it. Oh, I like doing this." That's just a bad habit. Like, I, I like doing this thing and it's a little bit bad for me. Like, you wouldn't say that students are addicted to procrastinating, even if they have a longstanding, deeply ingrained habit of doing it. It doesn't rise to the level of addiction because a- addiction withdrawal in psychology, in the clinical sense, is, like, very severe. It's, like, impacting your daily life functioning, and I don't just mean, like, you were an A student and now you're a C student. I mean, like, very y- big, you know, breakdown of relationships kind of stuff. And that's something that bothers me kinda out there, is this calling everything addiction, because I actually think addiction's this enormously sensitive, you know, profound problem in the world where we have a lot of people suffering, and there's been a lot of misconception about it. There's a great paper that is about, um, how easily we pathologize stuff that comes up with a measure of, like, being addicted to offline friendship, so, like, hanging out with your friends in real life. And they take one of these survey measures that people have used to study, quote-unquote, "social media addiction," and they, like, run it with people, but they just change the items to make it be about hanging out with your friends. And, and they're like, "Look, people are addicted to having friends, and they have withdrawal if you don't have them." You know, and it's just a way to show basically that these measures are bad. They're very badly constructed, and you can kind of create the appearance of addiction if you use these sloppy, broad, vague measures. So that's something that, you know, I, I feel like is really interesting to think about.

Ashley 18:40

Yeah. I, it really feels like we pick and choose the things we call addictive versus the things we call, you know, like pleasurable or just good for us or nice to have, you know? Obviously, I think very few people would disagree with the idea that friends are good for you, you know?

Cat 18:56

Are, are there like things that give us, quote, these dopamine hits that are not, you know, nobody's worried about? Like, I would think listening to music or video games. I guess, I guess some people talk about video game addiction, but that seems like an activity that we trust that a lot of normal people can do, and we're not, like, regulating it, you know, for addiction, right?

Ashley 19:18

Yeah, totally. I mean, probably when video games first came out, people were like, "Oh my God," like, "The kids are addicted."

Cat 19:24

Oh, they were. Yeah, absolutely

Ashley 19:26

I

Cat 19:27

there still is that in religious circles

Ashley 19:29

That's, yeah, no, that's fair. But, uh,

Cat 19:32

A- as you play Hades, Ashley's playing Hades right now, very intensely playing Hades. Are you caught in, like, a dopamine loop playing Hades?

Ashley 19:41

probably. I mean, yeah. I mean, I, I think the key thing here is that, like, things that are addictive usually feel good, but not everything that feels good is addictive, right? This is, like, something we have to tease apart. These things are not the same. Um, and, and you could replace dopamine for that, right? Like, things that involve dopamine usually feel good, but not everything that involves dopamine is addictive. Like, same, same logic. So right, your question, do video games invoke dopamine in your brain? Absolutely. In fact, that's the perfect example because this was probably the first time we ever measured dopamine release in humans, um, and showed that when people were playing this, like, kind of silly video game where they were, like, in a battle tank just driving around, like, collecting stuff, um, they had dopamine release in the same areas of the brain that, you know, signal rewards, so the middle of the brain. And, um, that was in 1998, right? That's not that long

Cat 20:47

how are we measuring that

Ashley 20:49

Right. So yeah, so this is probably one of my biggest pet peeves about the conversation around dopamine, which is it's very hard to measure dopamine in humans. So we have kind of one good main way, which is with something called positron emission tomography, and, or PET scanning.

Cat 21:11

ah, that's a PET scan,

Ashley 21:12

Yeah,

Cat 21:13

I didn't know what that stood for. Positrons, that sounds so 1960s sci-fi.

Ashley 21:18

Yeah. Yeah,

Cat 21:19

so w- what does a PET scan do?

Ashley 21:22

So in a PET scan, you first get injected with something, so it's actually a little bit invasive, which is one of the things that makes this difficult to do. Not everybody, even for 25 bucks or an Amazon gift card or whatever, wants to get injected with a radioactive tracer. Um, but that's what happens. And you use different tracers for different kinds of experiments. There's a particular one that people use for dopamine. And it's very cool actually, because what this tracer does is it gets into your brain, and then it competes with dopamine for the same sites it would normally bind to. So when you have more dopamine release in your own brain, dopamine's gonna out-compete the tracer, and the tracer, um, visibility goes down basically.

Cat 22:05

Oh, how neat. You're exploiting this mechanism of how these chemicals, like, connect to your brain Wow, that's so cool. There's so many little techniques in neuroscience that are, like, so clever like this

Ashley 22:16

Yeah. Yeah, totally. So many people have done PET scanning in humans and yeah, like, there's this 1998 study in video games. Um, there's a more recent study about music causing dopamine release. And then of course, you know, one of the biggest areas this has been used in is the study of drug addiction, And so, um, Nora Volkow, who was,, director of the National Institute of Drug Abuse for many years, she has, like, a whole body of amazing work showing how drugs like cocaine change the dopamine system, and this is largely based on PET scans like the one I just described.

Cat 22:51

Yeah. This is bringing something up for me, which is kind of this like maybe fallacy. You tell me. I'm thinking we sort of have this idea that, okay, if something happens in the brain in a really bad state in addiction, you know, really serious substance addiction, then the things that we see that we kind of analogize to addiction, like they're not as bad behaviors, but they're kind of bad. You know? Like, I'm not, I'm not able to pull myself out of the video game. We see it as kind of like a linear, well, what, what I'm experiencing must just be like step A, and then addiction to cocaine is step D. You know, it's like a linear process. So I'm just experiencing like a toy version of what's happening in addiction. And I wonder if that's actually true, because I think that might be like a fallacious way of thinking about the neuroscience of your brain. Like, there might actually be tipping points or thresholds or even like sort of similar looking behaviors could be driven by completely different mechanisms. Is that making sense to you? 'Cause I, I feel like I see this in my tech circles. People are trying to reach for these... There are certain things we know about the brain and our bodies that have only been studied in very extreme cases, like addiction, and then they're saying, "Yeah, well, okay, I'm gonna just pull that into my experience with having a bad habit, and I'm gonna say that it's the same mechanism secretly driving it." And I'm not... I'm like, "Hmm, do we actually have the evidence for that?"

Ashley 24:20

Yeah, I think that's a really, really good question. So I think the big difference here is like, yes, you get a little burst of dopamine in response to, like, doing something good as a reinforcement signal, and that happens when you play video games, it happens when you listen to music. It probably happens when you're, like, talking with friends, right? Like, anything that feels good gets a little bit of dopamine in your brain, as well as opioids and all the other stuff. But the thing that's really different and categorically different, like a phase change, in something like cocaine dependence, is your baseline dopamine and your need for dopamine reinforcement So it's no longer just the little burst that changes. It's like now your system needs more in order

Cat 25:05

That feels different. That feels like a different thing than just the hit itself. And, like, I'm thinking about how both you and I really like to try to pull things back to the systems level, and I'm thinking about things like, you know, in learning science, we talk about, yeah, everybody gets distracted or everybody has some inefficient strategies, but some people have regulation come in and bring them back into balance, and some people fail to enact that process. And I'm wondering about that with some of these neurotransmitters. If you're just talking about a single thing in the brain in the abstract, you're not talking about, like, all the other things that might come on board to, modulate it or bring it into balance. And, like, you could say, "Okay, the hit happens," but, like, there's a big difference between someone who-- and then your brain resets back to its homeostasis as it should versus someone who doesn't. Those are very different experiences

Ashley 26:02

Yeah. No, I absolutely, this is such a good point. And again, it comes back to this idea that, like, we're not just, like, a bad feedback loop, you know? Like, you have other mechanisms in your brain

Cat 26:12

Other feedback loops.

Ashley 26:14

other feedback l- like sure, it's, it's a lot of feedback loops. They're all happening all at once. It's very dynamic. It's very nonlinear. This is the brain, right? It is not as simple as, like, more dopamine, more reward, more good, I do more. Like,

Cat 26:26

And now we get to our relationship long conversation about determinism and reductionism

Ashley 26:33

Oh,

Cat 26:33

whether there's, like, a consciousness that emerges from all of these loops. But I lo- I, I love this because I think it's just so gr- one thing I try to do whenever I work with teams in the real world is I say, "Okay. All right. We've identified a bad loop." I mean, my s- mine's not biology. It's like you have a, a jerk pushing code in a way that you think is really unkind to you. And I always ask, "What happens next? What happens next? Do you talk to that person, or do you just ignore it? Do you passive aggressively make a bad pull request back? Like, what do you, what happens next?" And I think that the what happens next question is really, really helpful because it, it takes us out of this, like, cherry-picking explanations and into, like, the larger system

Ashley 27:17

I love that. And I would ask the same thing of people that are kind of like, "Okay, I feel addicted to my phone," or, "I feel addicted to this video game." I'm like, "I'm gonna get off this call and go play Hades." You know? Okay, and then your question is, like, what happens next? Like, you observe that, that habit that you've formed, right, that impulse. What do you do next? Do you, like, step out and you're like, "Okay, a better thing for me would be, like, taking a walk or calling a friend"? You know, like, is there a way that you interrupt the signal? And I don't think we need to call it dopamine fasting. Like, you know, and, and if you wanna go so extreme with that where you're, like, never gonna look at anything that causes dopamine... I mean, first of all, that's impossible because again, like, if you saw, like, a nice color, your brain would probably release a little bit of dopamine, so, like, good luck trying to avoid the dopamine all entirely. But also, you know, like, I just feel like you should call it what it is. Like, if you want puritanism, like, just have puritanism and don't use dopamine to make an argument for that.

Cat 28:19

You're, you're trying to reach for a brain-based explanation for why you think people shouldn't have fun and, you know, because you feel like people can't argue with it or something

Ashley 28:30

Yeah, I just, it's like, don't get the brain involved. It's, it's just so much more it's, it's just, like, so much more complicated than, than just a little burst of dopamine or a dopamine hit

Cat 28:44

Hmm.

Danilo 28:45

The people need to know if this debate about determinism and such instigated subsequent dates that kept the flame going. Please expand

Cat 28:56

Defi- definitely. Definitely. Like I can't resist an argument that I find interesting.

Ashley 29:04

Yeah, I would say we have this, like, argument maybe once every six months or something, like recurring. And actually, I remember one, we were actually in, San Antonio and... Do you remember this, babe? Like, we were in

Cat 29:18

Oh yeah. Oh yeah, of course I remember this

Ashley 29:19

probably the big first one

Cat 29:21

the big one and, and I was shopping for a wedding dress at the time and then came back to the hotel room and I was like, "Wait, can I marry someone who is a reductionist?"

Ashley 29:34

Yeah, and it was, it was really intense actually. And I was like, "Yeah, sure, I'm, I'm a reductionist." Like, I sort of like said it in a passing way like it wasn't gonna be a big deal, and Cat was like, "I'm sorry, what?"

Cat 29:45

To be clear, Ashley's my life partner forever. I was not questioning the relationship. I was more trying to figure out how am I going to find my path to understanding this? This has been like a long-running conversation in our relationship, yeah.

Ashley 30:00

still bought a wedding dress on that trip, so I'm gonna say it wasn't devastating.

Cat 30:05

Well, I think the, the fact is we talked about phenomenology on our first date, and I was like, "Oh, I think I could spend some time with this person because she knows Merleau-Ponty." And so that's

Ashley 30:17

I hung out with a lot of philosophy grad students at the time.

Cat 30:20

and you pulled it out on the first date, and that was a real green flag, and there were, like, some red flags. Like, I really, really don't like sketchy little dive bars. I, like, don't drink that much, and Ashley took me to, like, a sketchy little dive bar, and she was like, "Oh, let's get some beer." And

Ashley 30:36

I think I would call it a dive bar. They had a really good selection of craft beers

Cat 30:41

right, right. I wouldn't have even known the distinction back then, and I'm, like, showing up femme to the max, like heels, like that's who I am. And Ashley, at the time, 90% of her wardrobe was brewery T-shirts.

Ashley 30:55

Yeah. That's, that's true.

Cat 30:58

But, you

Ashley 30:58

I was wearing a gray T-shirt, and I actually met up with some friends afterwards, and they were like, "Wait, you just had a first date and you were wearing that?" Brutal. Absolutely brutal. I

Cat 31:10

We were all going through a

Ashley 31:11

tell them how it's going.

Cat 31:13

That's right. But then you were like, "Oh, Merleau-Ponty and the phenomenologists, and, like, what kind of philosophy, you know, are you interested in?" I was like, "Okay. All right. Let's talk

Ashley 31:23

And then, like, actually just last week we were at a park and somehow got to talking about reductionism again, and finally realized maybe Cat had a different idea of reductionism in her head. Like, in my mind, it was like I'm a biological reductionist, which is

Cat 31:39

I got a big, I got a dopamine hit because I was like, unexpected topic in this

Ashley 31:44

Unexpected

Cat 31:45

unexpected finding we have to do. Yeah, I got really reinforced, um, by that conversation to like ask you more questions.

Ashley 31:54

And then just this morning you sent me some survey of neuroscientists that, like, is about whether they believe in free will or not.

Cat 32:02

Yeah. Yeah. It's all delightful. It's all delightful for me to talk about. I mean, I think that, like, I had to pull it back to the podcast. Like, understanding what we're experiencing is hard, you know? And I think it's hard and it's scary. It's scary to watch yourself do things that you don't feel like you actually wanna do. You're like, "Why am I doing this?" And, and yet part of me wants to, and I don't know where that part comes from. I

Ashley 32:28

Hmm

Cat 32:29

it's this huge stack of things like our habits and then our I mean, chemistry's involved, right? Like, your physiology's involved, so. But I, I love regulation because I think it is such a helpful piece to bring in to say, "Look, you are also regulating this all the ti- you're go- you are actually When you move your body, that seems to modu- that probably changes what's happening with dopamine. Like, you're not a rat in a cage, you know? Even rats in the real world are not represented by their caged behaviors.

Ashley 33:03

Yeah. I have, like, a lot of compassion for our need to understand what we're going through and, as you said, kind of understand our compulsions. Like, absolutely. I mean, this feels like the fundamental human pursuit, like, understanding ourselves, and, and I want that a lot, but I, but I don't want it in the way that I think doesn't really take into account how complex it is in a really beautiful way. And, and I also don't want it in a way that takes what we want and our own abilities to regulate ourselves out of the picture. You know, I'm not ready to say, "Oh man, my dopamine sucks, and this is the thing that evolution has given me that I have no control over." Like, I just... That, to me, feels like the most pessimistic version of the story

Cat 33:53

Yeah. So now after going on this journey, I have a last question for you, which is, you know, what, what do we not know about dopamine? Like, what is a mystery? Like, what are scientists struggling to understand? Like, what are kind of some big open questions about dopamine?

Ashley 34:08

Hmm. Yeah, that's a great question. There are-- I've said that's a great question so much. I do that when I'm teaching. I'm sorry.

Cat 34:16

It's very professorial of

Ashley 34:17

yeah. Wow. Um, I think there's, I think there's a couple things. I'll name two. One is, as I said, it's really hard to study dopamine in humans. We have PET scanning. We can also do functional MRI, and that gives us insight into areas of the brain that signal with dopamine, but doesn't directly tell us if dopamine is the signal. Um, so we have these limited ways to study dopamine in humans, but we have actually a lot more work in non-human animals. Like, the initial experiment about reinforcement learning was in primates, was in monkeys, non-human primates, which I know you think is really funny that I say. Um, but that's, that's how we talk about it, non-human primates, because we're primates.

Cat 35:08

Part of this episode is just learning how neuroscientists talk, which was also part of our early relationship. Like, when they say something like decision-making they don't mean what we mean when we say decision-making. They're like, "Oh, these little circuits and all th-..." It's just so interesting. It's like, ah, we need a translation layer

Ashley 35:27

Yeah. Right. So, so I think, the first big thing is taking what we've learned in those animals and applying them to humans. And we have a lot of theories both from animal research and computation about, like, the precise kinds of computations that might be happening in different neural circuits that we don't know if they happen in humans because it's very hard to study in humans. We may never have some of those answers. Um, the best we've been able to get to, like, let's say single cell explanations of what dopamine is doing are the times when we have patients that actually have electrodes already implanted for something like Parkinson's disease. So one of the ways that we treat Parkinson's, in addition to giving dopamine, is stimulating dopamine areas

Cat 36:11

Right. So we can take advantage of some of these extreme situations because it gives us access to a form of data collection that... But that's a very specific, that's a very small, specific you know, not randomly selected group of

Ashley 36:24

Yeah, totally. Right, and then you have to ask, well, this is a Parkinson's brain. Does it actually signal in the same way that a normal, quote-unquote, brain does?

Cat 36:32

this is so interesting though because I, I think I didn't fully realize why you always see people talking about animals. Like, people are like, "Coding is, with AI is bad because look at what rats do." And I've always like, "Wait, you know, there actually is a, not enough human work on dopamine," so that's why people are pulling from these animal studies. And I think that from a stereotype point of view, that probably makes us even more think, you know, "Oh my gosh, am I just, I'm just the human primate." And that's kind of a scary thought for a lot of people still who aren't used to you know, understanding how brain evidence often comes from animal models and things like that. And so you hear these stories of, like, animal studies, and it just feels very scary. It feels like determinism that you can't escape. Hmm.

Ashley 37:20

Yeah, totally. And animal models are really useful. They are how we understand a lot of what the brain does. But at the end of the day, if you haven't seen it in a human, we don't know for sure that that's how it works in humans. So I think that's, like, gap number one right now. Um, gap number two, I think, is understanding, the different roles of dopamine and the different kinds of cells in the brain, because there's actually different kinds of dopamine neurons, not only in different areas of the brain, but even in a single area of the brain, there's different kinds. And if you're thinking of, like, you know, the logic on a computer chip or something, and you think about every neuron is talking to, you know, a few hundred other neurons, let's say, the identity of that single neuron matters tremendously. They're not all doing the same thing. They can make different computations. So I just think, like, ultimately, and this is kind of my bias showing as someone who likes to think about single neurons and not, blobs of brain activity, but ultimately, like, the answer comes from single neurons

Cat 38:19

Wait, I think I need you to, like, explain this a

Ashley 38:22

Oh, no.

Cat 38:23

f- I'm sorry. For someone who's not a neuroscientist, like, what do you mean, like, the identity of the single neuron? Or can you, can you, like, teach me a little bit more what you

Ashley 38:34

Sure. I mean, there are different ways we define cell types in the brain. We could do a whole episode on this if you want, but, we can define cell types by the other brain regions they talk to. And so, for example, there might be a cell in the middle of the brain that talks to the cortex and delivers dopamine to the cortex, and that's one sort of signal. There could be a cell in that same brain area that talks to another part of the brain, maybe a, quote-unquote, other reward part of the brain, like the nucleus accumbens. That's a different signal than the one going to the cortex. So yeah, we define neurons based on who they talk to. We also define them based on who they get input from. Every neuron is an input-output system, and so it's getting different forms of input. Um, and then finally, there's other really interesting things, like there's some dopamine neurons that are kinda constantly firing. Like, they're just like, doo, doo, doo, doo, doo. We call those tonic firing. And then there's neurons that do the bursty thing. Yeah, exactly. Exactly.

Cat 39:37

so this is complicating it 'cause you're like, there's really different forms of activity. There's different dopamine processes, even if it's the same category of neurotransmitter. What's actually happening with it and on what timeframe is actually very different.

Ashley 39:52

yeah, neurotransmitters are probably not the way to actually divvy up brain activity

Cat 39:57

Yeah, it's just an old-fashioned way

Ashley 39:59

Yeah. They're just like, i- in our world, electricity flows via electrons, and it's like, okay, maybe in a different world there could be 10 different kinds of electrons. You'd have like, you know, electron, dopa electron, serotonin electron. At the end of the day, they're just the signals that are getting passed, and it's not the signal itself that matters, it's where it's being sent and how and, like, to whom. So different neurons use the same neurotransmitter for different kinds of signals, and I think this is actually kinda coming back to big picture, like what is dopamine doing? It's actually just context dependent. It depends on what neuron is releasing it, and on what timing, and where in the brain.

Cat 40:41

It's

Ashley 40:41

not like we can say dopamine does one thing.

Cat 40:44

Seems like we need systems neuroscience

Ashley 40:47

Yeah, we need you know, better experiments teasing apart this stuff, which people are doing, right? But it's, it's tough and it's a slow-moving process but in the meantime, don't blame dopamine for everything