#413 ‒ The neuroscience of emotion: challenging conventional theories of emotion, how the brain predicts and constructs our experiences, and gaining greater control over how we feel | Lisa Feldman Barrett, Ph.D.

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If you'd like to learn more about the benefits of our premium membership, head over to peterattiamd.com forward slash subscribe. My guest this week is Dr. Lisa Feldman Barrett, a psychologist and neuroscientist who has spent more than two decades studying emotion, the brain, and how our experiences are connected by the mind. Lisa is a university distinguished professor of psychology at Northeastern University with additional appointments at Mass General Hospital and Harvard Medical School. She co-directs the Interdisciplinary Effective Science Laboratory. She's best known for her theory of constructed emotion, and she's the author of How Emotions Are Made and Seven and a Half Lessons About the Brain. I wanted to have Lisa on because her work challenges some of the most basic assumptions we make about emotions and the brain. Namely, her work challenges the idea that emotions like fear, anger, and sadness are hardwired neurologic states, as well as the idea that the brain is a part of the brain. So, if you'd like to learn more about how emotions are made, I'd love to hear what you think about the brain, and what you think about how emotions are made. Dr. Lisa Feldman Barrett is a professor at the University of Northeastern University at Northeastern University, and she's a professor at the University of Northeastern University. Instead, she argues that variation in emotional states, both within and between people, is the norm, and that the brain is fundamentally predictive in nature, and that the things we experience as emotions emerge from the brain's constant assessment and prediction of the body's future metabolic needs. In this episode, we talk specifically about how scientific averages can obscure meaningful differences between individuals, and why emotions don't have universal biomarkers, and why the variation in these emotions matters, why the brain is better understood as a predictive system rather than a reactive one, how memories and past experience fundamentally shape what we perceive, feel, and do in the present, why changing behavior can change emotion, and how deliberate practice can train and build new patterns of response. How the brain predicts and regulates the body's energy needs through allostasis, and why that matters for stress, the relationship between chronic stress, uncertainty, social connectivity, and physical health, and how losing someone you love, in a very literal sense, is like losing a part of your body's regulatory system, and how this framework can give us more agency over our emotional lives without pretending we have complete control. So, without further delay, please enjoy my conversation with Dr. Lisa Feldman Barrett. Lisa, it's so great to see you, and I know how busy you are, so I'm incredibly appreciative of you making the time to sit down with me today. I'm delighted to be here, so thank you for the invitation. So as we just discovered a few minutes ago, we both have this thing in common, having grown up in the same city. Um, but it sounds like we've both lived in our current home longer than our previous home. Indeed. Indeed. I want to kind of understand when the first time you appreciated the idea of emotions as a, as a topic for study. Well, when I was in graduate school, I, so I, I went to graduate school to, I decided not to go to medical school and, like all my other friends, and I decided to go to graduate school to be a clinical psychologist, and so obviously right away you're starting to learn about emotion and how they work and what they are and so on. And so I thought I had a pretty good idea, and I was doing research for my PhD, actually on a topic that was something other than emotion, but I had to measure emotion. And I did it in a pretty standard way, which is to ask people how they feel. What I realized, was that I wasn't able to replicate the experiment. So usually in graduate school, what you do is you take a published, a research study that's been published in a peer-reviewed journal. You try to replicate it just so that you can show that you know how to do an experiment. And then you go on and you do your own stuff. So I was preparing for my own line of work, and I tried to replicate this experiment, and I realized pretty, pretty early on into it that the findings were not replicating. So. I'll spare you all the gruesome details, but over a three-year period, I tried to replicate eight different, eight different times I tried to replicate experiments, probably a total of three or four experiments, multiple times, and wasn't able to do it. And my first response to that was, well, obviously I'm not cut out to be a scientist. Good thing I'll train to be a therapist. And then I took a closer look at my data, and I really realized that while I was not replicating the published work, I was replicating myself over and over and over again, which to me was an indication that something interesting was happening. And luckily I was working with research advisors who were willing to be persuaded by my observations. So I just can't resist pulling on this thread though, in that I want to hear some of the details of this. This was clearly such a pivotal moment in your career that it would be helpful, I think, for me and I think the listeners to understand the nature of these experiments, what was published and why you couldn't reproduce it, and perhaps more importantly, what it is that you kept reproducing that was distinct from the published findings. Sure. So usually when you ask people how they feel, you give them a set of adjectives, or sometimes it's a set of statements, but usually a set of adjectives, which are labels for emotion categories. And you ask people, how frequently have you felt this in the last week? Or how intensely do you feel this now? And in particular, I was really interested in anxiety and depression. And so I was also using clinical scales. In this case, I was using a number of clinical scales, but including the back depression inventory and the back anxiety inventory, where you're asking, you're giving people statements. You're giving people statements about symptoms, like I feel sad, I feel tired, I have no appetite. And you're asking people to rate the extent to which those symptoms describe their experience. And in the studies I was trying to replicate were basically, this was a, these were a set of experiments about the self, about your self-concept, where if you compare your beliefs about who you are right now. In relation to say who you ideally would like to be, or who you think you ought to be, maybe because your parents told you this, or there's some, you know, standard that you think you have to meet, that if you fail, if you compare your experience of yourself as you are to who you ideally would like to be, you would feel depressed. And if you were failing to live up to the shoulds, the oughts, then you would feel anxious. This of course requires that people can. Distinguish between anxiety and depression as feeling states where I wasn't really dealing with clinical samples at this point. But one thing that I found was that I wasn't able to replicate this effect because when people reported feeling anxious, they also reported feeling sad or depressed. And when they reported feeling happy, they reported an absence of anxiety and they would report feeling calm. They were basically reporting "I feel like shit" or "I feel okay" even though the instruments I was using gave them the opportunity to be much more granular, much more specific. Now, here what I was doing was what most scientists do, which is to test a group of people and then look at the averages, right, of the group and make inferences about it, about, you know, what you think is true based on what you observe at the group. And the way that I phrased the question at that time was very much dictated by what I had learned up till that point, which is that, you know, anger, sadness, fear, depression, anxiety, you name it, emotions are biological categories that are distinct and that people were having trouble identifying what emotion they were experiencing. And so my research was very much focused on that. But my first way of phrasing the question was, "Well, I wonder what ignoring, that is causing them to fail to recognize the emotional state they're in. And very quickly, once I actually started, I did more than just dip my toe into the emotion literature and read other people's summaries. I actually started digging into the papers myself. I realized actually that the phrasing of that question was in error, which meant something really interesting was going on that an entire field seemed to be missing. So Lisa, I want to just recap something there to make sure I'm understanding it correctly. What you just said actually answers a question I was about to ask, so I'll ask it only to make sure I understood. It seems to me that part of the difference was in the way you posed the question. Is that a fair statement? Well, at first I posed the question the way that I had been taught to pose the question, which is this assumption that there's an assumption, right, that this assumption is still very much with us in certain circles that, you know, human infants are born with circuits embedded in some ancient part of their brain for sadness, for fear, for anger, for, you know, there are a handful of. Categories. And that if you could find objective ways, meaning not self-report. So, and we can come back to what this means, objective, because I think this is actually a big, this is a big issue. It's a huge question. Yeah. But the assumption was that objective meant not the experience of the subject. Yeah. That you could measure something else about the subject, maybe their blood pressure or their heart rate, or you could look inside their brain, or you could look at how their face moves or whatever. But you could. In some way, determine, because these are biologically distinct categories with separate psychological features, that you should be able to diagnose what emotional state a person is in. And if they don't report that state, then that speaks to the fallibility of. It suggests that self-reports are very fallible because, you know, there are these objective states. So the assumption is there are these objective states, they're. Biologically distinct, that is, that the boundaries between these categories are in nature, right? They've been discovered by humans, not placed there by humans. And that there's some, all instances of fear or anger or sadness, any category, but let's just take fear. All instances of fear should have some set of features that make it fear and make a response fear and not something else like anger or sadness. That is, that all instances. Of course, there's a set of features that make it fear and make a response fear and not something else like anger or sadness. So of course, I wasn't phrasing the question with that degree of specificity, but basically I was like, well, we know that these are universal inborn states. So if people aren't identifying them distinctly, there's something wrong with the identification process. And that's where I started. And in the process of trying to look for an objective measure to diagnose someone's emotional state, I realized there are no, actually, objective measures. And so I was like, and that scientists have been debating this for 150 years. And I think at that point it would be more like 100 years since I've been at this for a while. And in science, it's often the case that when a debate persists for a very long time, and even before, you know, even really, I would say even before the scientific revolution, there were philosophers who were debating this. When a question has been debated for a very long time, there are philosophers who were debating this. And when a question has been debated for a really long time, it often means the question's wrong and that something else is going on. And because I hadn't been educated, schooled in theories of emotion and in the research, I came to it with like a blank slate, you know, I, and I also came to it with clinical training. And this turns out to be, I think, maybe important to the story because one of the things you learn to do, when you're a therapist, is identify when people are lying to themselves in your presence. That is, when they're telling themselves a story that just doesn't quite add up. And what I found was a massive story, a massive case of a story, not quite adding up, that there was a, I think at the time I would have said the dominant view, but I think at this point, I might say a dogma, a set of beliefs about emotion that were in the research literature. So what I discovered was that, you know, if you read the introduction sections of a paper and the discussion sections, they say one thing. But when I looked at the evidence in the results section, to me, it said something entirely different. And this said, you know, I don't want to be a therapist, but I want to be a therapist. And that set me on the path to where I am really today. I've changed my dissertation topic. I took an extra year to finish my dissertation because I completely changed my entire trajectory and did not become a therapist for very long. I was so enraptured really by the research process and the discovery that I just focused exclusively on that. So how did the previous scientists, explain variance in response? They do a couple of things with variance. So, I mean, think about. Like you alluded to it earlier. You said basically they just took an average. When you're angry, when you're angry, what do you do when you're angry? Do you make a scowl when you're angry? Sometimes. I mean, yeah, right. Exactly. Actually research meta-analyses, you know, statistical summaries of many, many studies of thousands and thousands of people show that in Western cultures, people, adults in urban settings, scowl about 35% of the time when they're angry. That's more than chance. So it gets you a publication in a good journal, right? But that means 65% of the time people are doing something else with their face. And half the time when people scowl, they're not angry. So if you used scowling as an objective measure of anger. Yeah, it's got horrible predictive value. Yeah. And I might just add that's a lot of what AI, I'm afraid, is doing. Yeah. And I might just add that's a lot of what AI, I'm afraid. Yeah. is doing right now. But, you know, that may be another topic. But, you know, you'd miss 65% of the cases and half the time you'd be wrong. You'd overhaul it. Yeah. Yeah. Actually, what I would say is, yeah, that's right. Yeah. You'd have both false positives and false negatives. And every category works that way of emotion. And it doesn't matter what measure you're using. It doesn't matter, you know, does the amygdala show an increase in activity during fear? Yeah. More than chance? Yeah. About 30, 30% of the time. It does. But it often doesn't. And you see amygdala activation in many, many, many instances of emotion that are not fear and also across a slew of other phenomena. So the way that people deal with variance, right, what do you do when you're angry? Well, sometimes you scowl, but probably sometimes you frown and sometimes you might even smile or laugh. Sometimes you don't. Sometimes you might remain silent, you know, and plot the demise of your enemy. You know, what, does your blood pressure go up, go down, stay the same? Yeah. It all depends on what you're about to do next, which depends on the situation that you're in. So emotions, when it comes to emotions, variation is the norm. People do a lot of different things in the same category. They feel, anger can sometimes feel pleasant. It's not always unpleasant. Anger sometimes distances people. It can distract people from one another. But other times it brings people together. And then there are cultural, massive cultural differences that we haven't even, this is just like within one person over situations, right? So I think part of what scientists do, the way to think about it, I would say, is that science, the world is complex. Reality is super complex. And scientists simplify in order to study things. And this is normal. And one of the things. They simplify is variance. They try to often control variance as opposed to measure it. So one thing you can do in an experiment is try to capture as much variance as possible and try to model that variance, try to figure out its structure and how to predict it. Another thing you can do is you can try to limit variability. And that's what experiments typically in emotion up to that point had tried to do. So they would limit the number of categories being studied. They would limit the number of instances being studied. So the sampling of people, the sampling of the stimuli, the triggers to provoke emotion would be limited. The specifications of the statistical modeling would be designed in such a way as to remove variance or to get rid of variance as error variance. And when you start to look a little more closely at the evidence, you can uncover that variance and you can even design studies to cultivate that variance, actually, to calculate the variance. to try to observe it. And in the end, that's, you know, that's what I turned to were methods like that. So Lisa, I'm hearing two things that are related in question, but they seem distinct to me. And I want to make sure that I'm understanding this because it seems to be the foundation of what was the widely held view at the time you were doing these experiments. The two things are we should be able to objectively measure an emotion. And again, I think that's a very straightforward proposition based on people's understandings of what's objective versus what's subjective. We should be able to not, we should be able to know your emotion without you telling us. Is that a fair way to say that? Yeah, what I would, yes, it is. But I just want to point out that always objectivity is within relation to the subject, meaning you should be able to measure something in a subject that the subject doesn't tell you. But I think it's important to also realize that measurements are never objective because scientists, a scientist, there's the synonym for a scientist's observation is the scientist's experience. I mean, sure, you know, you can quantify numbers. Well, that's why we have to, that's why we do blinding. That's why we want double-blinded studies whenever appropriate. Yeah, but you know what? You can have double-blinded studies, but if you think that a double-blinded study actually removes your theoretical view from your study, you're deluding yourself because all experiments are theory-laden. They're theory-laden in the way they're designed, their theory. That's not a bad thing. It just means if you recognize it's that you can't, you can never have an experiment that samples in a theory-neutral way. You can never have an experiment that runs statistical analyses in a theory-neutral way. This is a mistake. It's a mistake that scientists often make. Once you realize that you yourself have a point of view and even though you try really hard, you can double-blind things, you can, you know, there are a lot of things you can do to try to control the influence of your own point of view, you can't remove it. And as a consequence of that, you can take other steps, additional steps to try to control it that maybe aren't necessarily the norm. Can you give me an example? So let's take something, let's take the following experiment. I have a hypothesis that I give you, if I give you this pill, it will lower your cholesterol. So I'm going to take a hundred people and without knowing which ones are which, half of them are going to get the pill that I think will lower their cholesterol. Half of them will get a placebo pill. They'll take the pill for three months and before and after they start, we will measure their blood level of this cholesterol. So what steps would one have to take to remove as much bias as possible from that, besides the blinding, et cetera? What color is the placebo? How big is the pill? What are the other factors that are involved? You know, are your subjects, what are you controlling? Are you controlling what they, how much they sleep? Are you controlling what they eat? Are you controlling. But does randomization take care of that if I have a large enough sample? It doesn't take care. No. So here's the thing. This is the thing that this is now, fast forward 30 years now, okay? But does randomization take care of it? No. Randomization takes certain variants off the table for you to model, but that doesn't mean that it removes the variants from the causal complexity that is causing the phenomenon. And as a consequence of this, you can randomly sample a hundred people. You can run a study. You can, get an effect. That effect will not predict anything about any individual subject in your sample. The way that we get rid of variability by modeling, by sampling large samples and large numbers of people and modeling them, and then we try to replicate the average or the summary. An average or a summary is a statistical fiction. It doesn't actually let you predict about any individual. About the individual. Correct. Yep. And this, I think, is a super important point that, of course, people are discovering this, you know, in personalized medicine and so on. But, you know, this knowledge has been around for a good hundred years for sure. And there are reasons why scientists appeal to averages and summaries when what's real is variation. So what you're doing when you randomize is you're removing information, as opposed to taking a hundred people and following them over some period of time in their own lives. And then you see whether the effect, you get this, whether the pill works, you know, by doing, you can do a set of experiments where you can still have control. Or I would say you can run your hundred subjects, but you can quantify the levels of the other factors that you think matter. And then you run another experiment where you set them at a different value. So in this make-believe study, maybe taking the pill on an empty stomach versus a full stomach matters to its effectiveness. Or maybe, you know. There are genetic differences within the subjects that are not captured. Or, you know, maybe it matters how much you've slept or maybe it matters. So let me give you an example. To me, this is like the, like a great example. So there were these very, very clever studies that were done maybe 15, 20 years ago, looking at the response of people to viruses. And so these scientists, they were immunologists, they were psychologists, they were physiologists, that they did is they took samples of people and each person, they stuck them in a hotel room, and then they quantified everything about that, how much they slept, what they ate, you know, basically how much, you know, mucus they blew out of their nose. Like really, they were quantifying everything. And then they took the same amount of virus, viral load was identical, and they just placed it in each person's nose. And then they watched what happened. And they observed that depending on the experiment, there were about five, I think five of these experiments done or something like that. between 20 and 40% of people showed symptoms of respiratory illness. That means the majority of people did not get sick from being exposed to a virus. That means a virus is a necessary cause of a respiratory illness, but it is not a sufficient cause. You would not think that. But that's most of biology, right? Yes, it is. But if you, if you stand up in a medical school and, or at Grand Rounds, and you say to a bunch of physicians, as I have, do you think a virus is the cause of respiratory illness? They will, like 90% of people will put their hands up. Why does that matter? And it's not physicians only. I mean, like, it's like people, it doesn't really even matter what you're, what, you know, unless you are somebody who studies complexity theory, you probably think in terms of these simple causes. But in fact, you can't develop the symptoms without the virus, okay? But the virus is, if you're controlling viral load, the virus is not a sufficient cause. There are other factors that are causal. And those factors are also necessary, but they're also not sufficient. And so what you have is a complex cause. Yes, for sure. So there's two things there. Maybe the virus example is a bit tough because there's immunity, but maybe they normalized for previous immunity or previous exposure in the 60% that didn't get it. But I still think this, this line of inquiry around causality is relevant. Because if you can establish that the virus is necessary, but not sufficient, and that it plays a causal role, then the removal of the virus removes the condition, correct? For sure. But here's what I would say. In a large clinical trial, you do a large clinical trial, and you find that, let's say, I'm going to make up some numbers, but let's say 30% of people get, or have, show improvement on a placebo. And so that means that you need some, other much larger number in your, in your treatment group to, to show an effect. And let's say you only find like 40% of the people that the, the drug worked for 40% of people. And it's not statistically different from the placebo. Your conclusion would be that the drug is ineffective, but that could be wrong. It could be that the drug is effective for 35% of the people. Yeah. And it's not effective for other people because there's complex causation and there are more, there are multiple factors. So I do think that there is a problem when you're reasoning about the outcomes of individual people based on group or averages. Yes. And this is, you asked me, you know, how do people manage, how do scientists manage variants? One way we manage variants is we ignore it. Yeah. We collapse it. Yeah. And instead we should, we should be modeling it. And you give me any example of, you know, I mean, I, I think there are lots and lots and lots of examples where, you know, have my own personal examples that I've talked about on other podcasts, you know, where, you know, which I could go, you know, but where it matters. Feel free to share one. I mean, this is a fascinating discussion. I mean, you know, a number of years ago, I was diagnosed, as many people are, with Hashimoto's disease. And I went to see an endocrinologist. So that's like, you know, where your immune system is destroying your thyroid. And I went to an endocrinologist who was a great endocrinologist. He was super, super knowledgeable. And he said, I said, so what's the treatment? And he said, well, we just wait for your immune system to destroy your thyroid. I mean, he wasn't being flippant about it, but, you know, he said, well, wait till your thyroid is destroyed, and then you start taking synthetic hormones. And I thought, yeah, no, I don't think so. And so I did something that I often do when I'm dealing with my own physicians. I went to PubMed, and I just started to read about thyroid diseases. And admittedly, I'm not an expert, but, you know, I have some ability to read papers. And I found a series of studies which showed really clearly that if you give low doses of levothyroxine, which is a synthetic thyroid, you can arrest the progress. These aren't clinical trials. They're not large. And it doesn't work for everybody. So I went back to him, and I went, look at these studies. And he said, as you would expect, as I expected, yeah, but there are no clinical trials. And so then I explained the thing. And he said, well, I don't know. I don't know. I don't know. I don't think about averages. And then I said, yeah, but it seems like it works for some people. And maybe I'm one of those people. So let's do a little experiment. And he was game because, you know, I mean, it's not terribly dangerous to take a low. I mean, there are some things you have to work out, watch out for. But we did it together because, you know, he was very, we were, we had an open dialogue. And sure enough, not only did it arrest the disease, it actually, you know, it actually reversed some of the damage. Now, and sorry, just to make sure, does that mean that your antibodies went from positive to negative? It means no, it means that like nodules disappeared from my thyroid. And, you know, so what it means is that the damage was that the antibodies went down. The damage was actually first arrested and then eventually started to reduce a little bit. And now. Now, you know, I'm kind of like a borderline case. I was not a borderline case to begin with. It should have progressed, but it didn't. And I'm not saying it's magic. What I'm saying is that this is not something that everybody who has thyroid disease should do. It's not going to work for everybody. Studies already show that, but it will work for some people and it worked for me. And this is one example in many, many cases where when you set aside the averages, what the averages tell you. And you look for variation and you look for meaning. I mean, it could have happened that it did nothing, but that's not what happened in this case. That doesn't necessarily mean that, like I said, that this will work for everybody and it won't. And it might not work for me forever either. But the thing is, so now I'm on a low dose of levothyroxine and I'll be on that low dose for the rest of my life. But that's better, I think, to still have a thyroid and be on this low dose than to be on a much larger dose and not have one for the rest of my life. I guess I just would, to me, this is just an example. It doesn't prove anything, but there are many, many, many, many published studies which do make the point that averages hide meaningful variance. And this is the case. This is absolutely the case when it comes to the science of emotion. Averages or statistical summaries hide meaningful variance. That is important in everyday life. So if you construct your experiment in a way, in a lab, in a way to get rid of variance, you are creating a fiction that will not predict anything in the real world. Yeah, I couldn't agree with you more. Let alone replicate. No, no. I mean, I agree with everything you're saying, Lisa. I probably, on a personal level, frame it a little bit differently. back to you, but I completely agree. I have sort of a way that I talk about this in the context of my world, right? So I talk about this thing called Medicine 3.0, and I contrast it with Medicine 2.0, and I say one of the limitations of Medicine 2.0 is it homogenizes data, which is just basically saying what you're saying, right? The bedrock of Medicine 2.0 is the randomized control trial, where we take a very heterogeneous group of individuals, we apply a clean, homogeneous treatment, and then we homogenize what comes out, and that becomes the recommendation. And on average, that is an excellent way to practice medicine. Well, I would say on average, it's a better way to practice medicine than the other ways, for sure. Yes, yes. And then where I think we would agree is the challenge with that is the variability gets lost. There's nuance that gets lost. So I'll give you one example from my world. There's a drug called Zetia or ezetimibe. It is a cholesterol-lowering drug, and it has a very specific mechanism of action. It works by blocking one of the transporters on the cells of the gut and the liver that reabsorb cholesterol. Now, when you look at the clinical trials of Zetia given as monotherapy, it is rather underwhelming. And without getting into the nuances of it, there was a huge debate as to whether anyone should ever receive Zetia and monotherapy. And it was viewed as not an evidence-based approach because it didn't have the hard outcome trial that said, if you give Zetia and monotherapy, you will save lives. But once you understand the mechanism of how ezetimibe works, and you understand that we can measure a person's cholesterol absorption using other biomarkers, we could selectively target people who are very high cholesterol absorbers. And those are the people that would do very well in monotherapy. And lo and behold, we do this now. This is what I would call precision. And I think there's still a lot of pushback to that approach. And I would argue that what you've pointed out is another example of that, which is to say, on average, giving Zetia as monotherapy probably doesn't save lives. But if you could target the people who are super responders. Yeah, for sure. For sure. For sure. So let me just be really clear. I'm not saying we should throw out clinical trials. No, no. And I want to make sure that the listeners hearing. You and I are on the same page. Yeah. I think what you're saying is very. Very important. And to me, this is exactly where AI could make an improvement in how we interpret clinical trials, because we wouldn't have to hide. We wouldn't have to try to compress variability. We could actually explore it more fully. Well, I think. So you're talking. There are two things that you're talking about now. You're talking about how science should be conducted and then what AI can do or not do. And those to me are similar. They're somewhat separate. Because it all matters how you. It matters a lot how you use AI. Well, let's put a pin in the AI. Let's come back to it, because I want to talk about it in the context of your work as well. Yeah. But what I will say is this, that in the science of emotion, there are no biomarkers. Okay. So that. There are no biomarkers. There's nothing analogous to the example that you gave. Yeah. And I. But I would also say that, and maybe this is what, you know, medicine 3.0 is. I don't know. But, you know, but. But I would say there are a lot of very brilliant people who, if they put their minds to it, could figure out other ways to do science that didn't require using group averages. So what you describe here with this example is a great innovation to patch up what is wrong with a clinical trial or use a clinical trial in a way that minimizes the. Problems with it or the costs. And I think that's great. And again, I would say I wouldn't throw out clinical trials just now, but I do think it would be worth thinking about other ways to do science. We do have opportunities and options to do things differently if we decided to put our minds to the technology and the money that it would cost. You know, what I often say to people is, listen, do you think that. Do you think that. What did it cost to build the Hadron Collider? Like, how many billions of dollars did it cost? Yeah. Okay. How many countries participated to discover the Higgs boson? It's because they thought it was important. Do you think. I mean, I would love to see what a bunch of. What medical science could do with that kind of cooperation and that kind of money focused on one problem. I mean, they built this. I mean, I'm not saying it's good what they did. It's just that that kind of ingenuity and cooperation and financing is not available. Maybe it's available in some circles in medicine. It's certainly not available in behavioral science or in neuroscience, frankly. And so they did something very clever. I think there are other clever things that we could do now. There is the technology that's available now to start doing experiments differently. You just have to have the ideas, the will, and the money to do it. Okay. I want to go back to one other thing that you said at the outset that I think is important for us to ground ourselves in, which is part of what maybe we would call this foundational belief you came into. So one of them we've just talked about, which is the objective measurement of emotion. But then there's something else you talked about, which is a belief that emotions are universal, that emotions are hardwired into our nervous system. And it sounds like you were saying, no, I don't think that's the case. These two observations that emotions are not hardwired into our nervous system and that we don't have an objective way to measure them with a biomarker, those don't require each other to be correct. Those are independent observations, right? No, exactly. And also, I mean. I think it took me, oh, geez, probably a good 20 years before I was willing to say that there was no biomarker. I mean, because I had to learn a bunch of literature. I had to retrain basically three times in order to be able to make that claim. I think one of the things that I became. I think I became very clear in my own mind about was that I wasn't going to be able to rely on the summaries of other scientists. I wanted to be able to collect the data and observe myself. And I also wanted to be able to dig into their studies and understand for myself. So basically, I was taking a very empirical stance towards published studies. When graduate students sometimes ask me, what do you do when you read a paper? I say, well, I read the few sentences in the introduction that outline the hypothesis. I read the methods and the results, and I throw the rest away. I don't read the introduction. I don't read the discussion. I don't care. I want to make my own judgment about what I think that shows. And then I will go back and maybe read or maybe ask colleagues who I trust. I'm very aware of how theory-laden publications can be. And so it's not like I ran a couple of studies in graduate school and came to this conclusion. I ran some studies in graduate school and discovered I had to learn how to measure facial movements objectively. And then when that didn't pan out, I had to learn physiology so I could measure physiological patterns to see if there were objective biomarkers. And then when that didn't pan out, I had to retrain in neuroscience to be able to do brain imaging to check that. Right? I mean, so I'm not, these are not conclusions. Same thing about universality. We didn't, I didn't just read a bunch of papers and test a bunch of college students. Our lab went to Namibia and we tested the Himba, you know, who live in Northwestern Namibia. We went to Tanzania and tested the Hadza, hunter-gatherers. We went to rural China and tested the Hadza, hunter-gatherers. We went, you know, so of course we use other people's experiments too. We use their data. We use their studies to draw conclusions. But we didn't only do that. We also went and did our own studies where we used multiple methods. And it's very, very clear what you find. The findings are really, really clear and they're clear across domains. It doesn't matter what you measure. Variation is the norm. There's structure in that variation. It's meaningful. It's not that we can, it's not that it's random. It's not that we can't say anything important about emotion. And also I didn't come up with my own views on what emotions were or, or how they work right away. I really spent really many years trying just to figure out the simple answer to the question of, are there biomarkers and is there universality? Like, and what is it that, you know, what do we do? And then I started to think about, well, we have a real paradox here, right? I experience emotion and I'm pretty certain about what I experience and I'm sure you do too. And you and I could be, you know, at a coffee shop having a conversation and I would, I would feel like I was reading your emotions and you would feel the same. So how is it that this is, that this is the case and then there are no biomarkers? Like this just felt like a really big puzzle. If it makes you feel any better, Lisa, in, in, in the world where I spend all of my time, we don't have a biomarker for aging. Now think about that for a moment. Is there anyone listening to us that disputes that we age? No, of course not. We, we are aging. Do we all have a gestalt of how somebody is aging? Sure. I can look at a person who tells me that they're 60 and I say, gosh, they don't look a day over 45. Okay. They're probably aging slower, at least in some dimensions. Of course, I can't see what's happening inside their body. And yes, on average, we can measure things that are changing as a person ages, their bone density goes down, their muscle mass goes down, they become a little bit more insulin resistant, et cetera. But to actually suggest that at the individual level, I could measure anything in you, Lisa, and then do an intervention and then measure it again in a year and definitively conclude I have slowed your rate of can do that, it is absolute nonsense. I mean, this is challenge. I mean, this is brutal. It's a brutal reality. Well, I don't think it's a brutal reality. I think it's a reality. And I think that reductionist science isn't the method to get at that brutal reality. So does that mean you've given up on the biomarker? Do you believe that in 10 years we will have biomarkers for emotions? No, I don't think it works like that. Okay. What I will say is if I measure you personally, Peter, many, many, many times over many, many, many situations, and I used a personalized AI for you, I could probably learn to reasonably predict the vocabulary of angers and sadnesses and fears and so on. that you experience. That's what I think is plausible. So, but that requires- But that won't, you can't use that in an experiment you do with 100 college students, right? That wouldn't help you as much. Well, you, well, what you would have to do is, my guess is that there would be some, you could assess the degree of similarity between people. So you and I grew up in Toronto, probably approximately. Around the same time. And that means we're similar, at least on that dimension. We both grew up around horrible Toronto Maple Leafs, Harold Ballard owned the league, like literally the worst team in the league. Okay. Yes, that's right. We share a number of things in common. No, there are other aspects, you know, that we share, like we're both melanin challenged, right? We don't have dark skin. Well, there are differences, obviously, you know, you're a man, I'm a woman, you know, so, but the point is that, there are some features on which we're similar, and there are some features on which we're different. And it's an empirical question as to which features matter to be able to use, to be able to generalize, to find, you know, well, you know, you can look for similarities in the algorithms that predict individual people and potentially inductively discover how, whether that similarity exists and, and, and how to capture it and model it. So what I'm saying is that it's possible that, that there could be more generalized algorithms, but you would not start with the simplification. You don't start with the simplification of getting rid of individual variability. You start by modeling individual variability, and then you look for places where you can reduce it on the basis of empirical evidence. That is a justified way, I think. It's just a much more cumbersome and expensive way to do the research. And it has huge implications for the incentive structure, and science would have to change, and a lot of things would have to change if we did research that way on a large scale. But it all comes down to what people care about and what they want to invest their research dollars in. And, you know, that's not for me to say. That's above my pay grade. So what, what can, what can we say about an emotion? If you were now trying to explain to somebody what emotions are, we've, we've said two things that we know on the negative. We know that they can't be measured objectively, and we know that they are not necessarily hardwired into each of us as identical states. Fear is not universal. Let me ask this question. Yeah, let me ask this question. Peter, what is hardwired into the brain? What is hardwired? Yeah, that's a great, I mean, I think certain reflexes are clearly hardwired. I think certain reflexes are clearly hardwired. I think certain reflexes are clearly hardwired, right? So for example, if I shine a bright light into your eye, I think it is hardwired that your pupil will constrict, right? It will, but how much will it constrict? And you know, even reflexes, which are hardwired, are not hard. They don't always look. The degree to which, sure. Yeah. Yeah. No. Well, but that matters, I think. So what I would say is that there is very little in, it's just like genetics, right? I mean, they're sure there are some cases where a single gene predicts a single characteristic, you know, with a single allele, right? I mean, but those are really rare. Most of genetics doesn't work like that. And I'm certainly not the first person to point out that, you know, NIH spent a tremendous amount of money trying to map the human genome on the assumption that that, you know, would actually, if we just knew the genes, we'd be set. A lot of the devil is in the detail. Of how, of the mechanisms, right? Because of this complex causation that happens. And I would say the same is true in the case of emotion and pretty much in the case of anything a brain does. So, first of all, I would not, when someone asks me, how do you define emotion? I say, I don't. You can't. How do I define, I could, the way I would define it would be generic. It would be like, well, any mental event basically could, you know, they, your brain's most important, most important job is regulating your body, coordinating and regulating your body in the most efficient way. That's why brains evolved. They evolved for, they evolved at the same time as invertebrates. I'm only speaking about vertebrates. I don't know anything about invertebrates, but invertebrates, they evolve around the same time as you get visceral organs and, and, you know, a head and distant senses and eyes and, and ears and so on. Let's probe that a little bit more. So, so this, I think you, you said, you said something in passing that, that is a pretty big idea, right? You said that the, the purpose of the brain is to support the body. Can you double click on that a bit more? Yeah. So I wouldn't, I'm, I'm trying not to be tear, I mean, I was a little sloppy and a little teleological about it. So I, I would prefer to back up and say like the brain's most important job. I'm not saying it's, it's, that's its sole purpose, but I think that, um, its most important job is regulating and coordinating the systems of the body and everything. I think everything it does, psychologically speaking, it's doing in the service of that. And that means that metabolism writ large is important to things like feeling and thinking and remembering and, and so on and so forth. So that's a key assumption in our lab that we use when we're designing experiments now. So what I would say is the brain is always receiving signals from the sensory surfaces of its body. Your brain is always receiving signals from the sensory surfaces of its body. Your brain isn't running a model of the world. It's running a model of your body and the sensory surfaces of your body. And of course, some of those sensory surfaces take in signals from the world, some of the signals from the world, but it only knows the world through the body. There's no other way to know a world than through your own body. So your brain is running a model basically of signals from the sensory surfaces. It's attempting to predict those signals and give them meaning. Because those signals that it's receiving are the outcomes of some set of changes that the brain doesn't have access to. It only has access to the outcomes, the signals themselves. And that's an inverse problem. It means the brain has to infer what caused that loud bang, what caused that flash of light, what caused that tug, what caused that change in glucose. It has to make inferences about that. And sometimes those inferences are emotions. And sometimes they're not. Okay, I'm going to ask a question that I never, yeah, this is a question I personally struggle with, which is, how do we define consciousness and how does consciousness overlap with emotion? So, yeah. I could see the look in your face. I intuited your emotion when I asked that question. And the valence is negative. Why? Well, what I would say is that, why is it? Because I think, I think that there are a lot of questions that you could answer about emotion without having to take on the big question of consciousness. But, but I would say the following, I guess, that I don't know if it's that we're asking the wrong questions or asking questions in the wrong way, but a lot of people have a lot to say about the nature of consciousness, none of which actually explains why. But I think that the question is, how it is that we are sentient and how it is that we have content, that there's content, that we get content out of, out of electrical and chemical changes. And I just prefer not to speculate. It doesn't mean that I'm not interested. It doesn't mean that I, I'm not curious. I'm, I'm very interested and curious, but I also, I'm not a fan of talking out of my head. Yes. You know, like I just, I think that we don't know enough maybe yet to ask the right questions or whatever. So we should continue to explore and debate and whatever. But, you know, like people publish books and they make claims about consciousness. So here's what I have to say. Are there aspects of emotion that you're not conscious of? For sure. That has to be the case. You're not conscious. You're not conscious of most of what goes on inside your own body. Thank God. Because if you were, you'd never pay attention to anything outside ever again. Just think about the last time you ever had like gastric distress. I mean, you just can't, you know, you can't focus. It's, there's so much going on in there. Right. And we don't have access to most of it. Most of the details are compressed out of the signals before they reach the brain. Right. And so, you know, I think that's, I think that's a great point. The primary visual cortex has a map of the retina. There's array to array mapping, meaning you have an array of cells in your retina. You have an array in your brain. They map. The mapping changes all the time. Right. So what a, like we would say the receptive field of a V1 neuron, a neuron in primary visual cortex changes actually with the context of, with the neural context of the brain. But it's always the, it's always a map. Right. But there is no map of the body like that in your brain. Just like there is no map of your olfactory, there's, you know, you have olfactory receptors in your nose. There's no map. There's no spatial map in your brain. That information is compressed out of the signal before it ever reaches your brain. There's temporal information, but not, not spatial information. In the body, the brain has like, it can tell, there's some spatial information, like is, is a signal coming from the brain? Is it coming from the thorax? Upper thorax? Is it coming from the gut? You know, lower, it's not even gut so much as like lower part of your abdomen, upper part. There's like a little bit more detail here, but it's nothing like a retina or a cochlea where you have array to array mapping. This turns out to be super important. In science, people talk about extericeptive versus intericeptive, like signals that come from the world versus signals that come from the body. That turns out not to be so important, I think. I think what's more important is, is it a proximal sense or a distant sense? Meaning the, the distant senses, the best examples are vision and audition. They're processed, the signal processing, the compression of those signals is very different in the brain than say olfaction, which is a proximal sense or gustatory or anything intericeptive. Gustatory is usually considered intericeptive. Taste is not, but gustatory, you know, signals from the gut are intericeptive. So, and then there are a bunch of signals that kind of don't fit the extericeptive in the internal, external distinction, like proprioception. Is that internal or external? It's kind of both, right? So if you just look at the signal processing, the signal processing properties, then other distinctions become important. And I would say it's the same thing about cognition and emotion or thinking and feeling. There aren't a lot of distinctions that you can find in the brain. There aren't a lot of distinctions that you can find in the brain or anywhere else to distinguish what is a thought and what is a feeling. But there, if, but if you look at the signal processing, you know, architecture and dynamics, other distinctions become important for explaining how a thought arises or how a feeling arises. None of those explain how you get from, you know, um, A very, very high dimensional set of chemical and electrical signals to a very low dimensional set of chemical and electrical signals. low dimensional mental feature like pleasantness or unpleasantness. Nobody has that. And if they're claiming to, which some people claim they do, then they're lying either to you or to themselves, probably to themselves in your presence. So let's try to disentangle, without defining an emotion, some of the broad differences between, say, the positive and negatively valenced emotions. So again, we'll go back to this idea that there's a belief that, God, some of these are really primal, like I'm going to anthropomorphize this as well, right? So fear is so essential, right? Without fear, we could not have evolved as a species. We couldn't have figured out a way to avoid predators or things like that. So let's just start with fear. What is it that you could say today we know about that emotion? Well, I'm just going to let the point go about we couldn't have evolved without fear. It's a primal emotion. And by the way, feel free to attack that point, by the way. No, I don't think I want to attack that point. It's just I don't think that's going to take us down a productive avenue. But here's what I'll say about fear. There are no pleasant or unpleasant emotions. You think fear isn't pleasant? People pay money to go on a roller coaster. They pay money to go to a horror movie. I used to run a haunted house in my basement for charity for 13 years. I don't know if you've heard of it. It's an auspicious number where we scared the shit out of people. We donated all the money, but we scared we basically tell people I scare little children for for I scare, you know, I have their parents pay me and I scare little children for money. And then I donated all to the Boston Food Bank, which is what we did for years and years and years. And we had three levels of scary, you know, some people could choose and and all of my. But is that is that a uniquely is any evidence that in that anything else in the animal kingdom will voluntarily put themselves in a situation that produces fear? Yeah, absolutely. I mean, there are and there is a there is a whole literature on how animals play and they're often playing in ways that would, you know, that could be considered practice. Like it's a way of foraging for information and for like innovation, basically, they are feeling fear. I can't comment on that. But what I would say is that you don't have access to whether an animal what an animal feels. If you look at an animal and you say that animal is fearful, that's your experience of what those signals mean out of that animal. And that doesn't necessarily mean that it tells you anything about what's actually going on inside that animal from a feeling perspective. However, I think you can say like if you watch an animal work hard to provide certain stimuli that will cause it damage, right? Or if you if an animal is willing to like expose it. So you there are these studies, you know, where they'll like damage an animal in some way and then the animal will actually work hard and even expose itself to the possibility of a predator in order to get an opioid. That's a pretty good indication. I think that the animal is feeling something like pain. Maybe not the way we feel pain, but it's definitely feeling something unpleasant because it's willing to incur a cost, a significant cost in order to get a drug that will reduce presumably its awareness of the maybe an awareness of the but you know, it's feeling in relation to some kind of tissue damage. That's very different than what like a fly will do, you know, where it does, you know, a leg of a fly or a wing of a fly, and it will still continue to behave in exactly the same way, then you know, you can sort of make inferences that way, which I so I'm not talking about pleasure and pain. I'm talking about the specific, the specific categories and distinctions that we make about humans that come from human experience. You have to be super careful when you impose those on other creatures, to which for which we have no access to what they experience. And I'm not so I'm not advocating to assume that they experience nothing. I'm saying that you just have to be careful. And there are lots of reasons for being careful, both for them and for us. But what I would say about fear is that, you know, what would you think is the prototypic response in fear to freeze or to run away? Well, you know, I think it varies. And by the way, sure it does. But I mean, the theory is, in the literature, if you ask most people fight or flight, you know, they're like flight. Flight, they'll freeze, an animal will freeze, you will freeze, or you will flee. But there's a, you know, a culture where what people do when they feel afraid is they go to sleep. That seems weird to us. But you can look in the animal kingdom, and you can find out that in invertebrates in the water, animals, when there's a predator, will play dead. They will slow their heart rate, so sharks can't find them. They will not move. They're not freezing. They're reducing their detectable output, so that the predator can't find them. So I think, I guess what I would say is, when it comes to fear, what we could say is that variation is the norm. What you feel in fear, what you do in fear depends on the situation that you're in and what you're going to do next. Because your brain doesn't react to things. It predicts. And those predictions always begin, always begin as motor predictions, as visceral motor predictions, predictions of what to do with the viscera to support skeletomotor predictions, whether it's to move your limbs or just to move your body. To move your eyes and your head or to not move at all. All predictions begin as motor predictions. And copies of those motor predictions become the expected sensory consequences of those movements. So your brain is preemptively. So what is an emotion? It's a set of predictions that tells a story about what a set of sensory signals mean to you in that situation. But that's not a specific answer to emotion versus cognition versus perception, because that definition encompasses all of those. I could say, well, emotion is when there's some really big change. And it's what I just said. Plus, there has to be some really big change in, you know, your level of energy or arousal has to go up or down a lot from what you're feeling. Where you are right now in order for you to experience something as an emotion. And that would hold that that aspect would also hold for many, many people around the world, but not everybody, because in some cultures, emotions and cognitions are not separate. In some cultures, emotions and bodily states are not separate. They're considered to be a single set of categories. Can you give me can you double click on that a little bit? So I understand what you mean. The bodily state and the emotion for anger would be the same for every person. No, no, no. What I'm saying is that in some cultures. So in our culture, we make a very firm distinction between is this an emotion or is it a physical state? Like, is it, you know, do you have a stomach ache or are you angry? Right. But when I'm angry, I can feel something in the pit of my stomach. So what is the difference there? But you wouldn't look. I mean, there's look, there's neurology, there's internal medicine and there's psychiatry. And what's the origin of those of those disciplines? The origin of those disciplines is where they think the cause is of the problem. And there's there are diagnostic categories that that you use when you can't figure out medically what's wrong with someone. But, you know, they're having some what, you know, difficulty in with mental features or what we would call psychological features. Right. Right. And the assumption is that it's all in their head, meaning it's not in their body. I mean, I'm not making this up. This is this is how things were for a very long time. So sure, it's the case that like when you're anxious, you you might have, you know, your heart might race or you might have gastric distress or whatever. But if you think gastric distress is the problem, you'll go to an internist. And if you think that your mood is bad, you'll go to an internist. And if you think gastric distress is the problem, you'll go to a psychiatrist when, in fact, they are related. So I'm not talking about what I think is the case or what you think is the case. I'm talking about what a lot of people, including a lot of physicians, think is the case. Physicians, I've had physicians talk to me about how depression causes heart disease and heart disease causes depression. Or another possibility is that they're both rooted in some set of metabolic problems. And one is not causing the other in the way that A causes B, like a metabolic problem. mechanistic cause. It's that they have a common cause. That makes both of them more likely. That's a very different way of seeing things. And so what I'm saying is that there are some cultures who wouldn't say, like in our legal system, we have thoughts. You can be culpable because of what you feel or you can be culpable because of what you do. And there are different punishments for that. But there are some cultures where thinking and feeling are the same. They are features of the same state. So you wouldn't call something, you wouldn't distinguish between a thought and a feeling because they're both, it's like you have thought feelings. There's just, it's not one or the other. They're both, you know, it's like blue and green together make turquoise. You wouldn't say it's blue or it's green. You would say it's turquoise. It's both. They're not distinct states. Similarly. there are cultures where there are somatic descriptions for emotion. Like that is the nature of emotion in those cultures. So we need to have a theory of how a brain and a body together in a world full of other brains and bodies create a mind. And that has to work for everything. And that has to work for everybody on earth. It's not just to explain Western categories. And that may mean that emotions and thoughts and perceptions are things we have to explain, but they are not themselves explanatory categories. They're not categories that explain anything. So, are you saying then that the universal theory that is culturally agnostic is that the goal of the brain is to, well, there's two things I've heard. One is the, a main priority of the brain is to support the body physiologically, metabolically, etc. And two, the brain is a predicting machine and emotions are arising out of predictions of physical sensations or the consequences thereof. Is that directionally what you're saying? Yeah. I mean, I would never claim that it's culturally neutral because I, you know, can't claim that. I'm, I live in a, I was pickpocketed. I was pickled in a culture just like you and there are other, but, you know, I think, I think that it's a reasonable, it's a reasonable hypothesis. But if it's biological, it should, I mean, it doesn't matter what culture you live in. There are certain biological things that are true across the board. I'm just being, I'm being a little humble here, Peter. Biology in Western science, I'm not, I'm not immune to, I don't, I don't think, I'm just being, I don't think it's viable. I don't think it's relevant to say, I don't, I wouldn't claim, I'm trying to think of how to say this without being too negative. I'm very aware of the fact that some of the beliefs that I hold as a scientist come from the fact that I was raised in a Western culture and I use Western concepts and methods of science and not everybody, you know, adheres to that. But I would say that I can defend. I can defend that statement by looking at anatomy, by looking at physiology, by looking at brain evolution, evolutionary biology. I can defend it by looking at developmental neurobiology. I can defend it by looking at signal processing and engineering. I think that when multiple fields come to the same conclusion using completely different sources of evidence and they don't talk to each other all that much. That's. Then you know that you're probably on to something. The idea that the brain predicts and doesn't react is, is actually a concept that is in other cultures. And it's been in our culture for many, many, many years, like, like centuries. But this is very counterintuitive. So I really want to spend some time on this because I've always felt that my brain is just a reaction machine, right? Like I'm riding a, I'm riding a bull. And that sometimes that bull is just walking. And everything is fine. And sometimes it's bucking like crazy. And my vertebrae are getting crunched. So let's maybe in any way you like, let's go through the different lines of evidence as you've laid them out from different sort of empirical disciplines to how we can say that the brain is, is not reacting. Sure, sure. I mean, just before I do, though, I just want to say two things. One is, so for you, it's a bull. And for John Haidt, I think it was an elephant. And for Plato, it was two horses. Two horses and a charioteer. You know, like that idea that we have an inner beast that we have to tame and kind of control is wrong. It feels that way. It feels that way to me. But it's not defensible. It's not a great metaphor because it doesn't really reflect, doesn't really reflect the evolution and anatomy of the brain, for one thing. So that was my first, that's called the triune brain. And it's just, you know, it's really, really popular. But the evidence against that. It's been in molecular genetics for at least 50 years, if not more. So that's just, we just have to take that off. I just finished doing a video, actually, with a videographer, just kind of do like a, to explain why this is not the case. And show, for the first time, you know, a depiction of how a common kind of manufacturing plan for a vertebrate brain could produce all different kinds of brains in vertebrates. Really, it's just mammals. But you could make inferences to vertebrates, I think, in general. The data is just about mammals. But you can get a mouse-looking brain and a human-looking brain out of the same, exactly the same manufacturing plan in an embryo. That's not my work. That's work by Barbara Finley and her colleagues. So that's the first thing I want to say. And I can't even remember what the second one is. Well, but tell me why my feeling of. Oh, your feeling. Of this, of riding the bull. Well, that's a question. That's a super interesting question. Yeah. That was my second. Thank you. That was good. Thanks for that assist. Yeah. My second point is that your feeling isn't evidence of anything and neither is mine. Yeah. Couldn't agree more. Yeah. So, so I think brains are amazing, right? Because they're like masters of deception. They create experience kind of seamlessly. And that experience reflects nothing about how it, they work, but yet, you know, we're, they, they're very tempted to use it that way. I was like, so I think that, why is it that we experience things that way? That is a great question. That is a great question for science. Somebody should study that. Because it isn't really good evidence, but it is a phenomenon that is worth studying. Like where does our, so some people study, like, where does the memory come from? And where does the certainty about memory come from? Because they're not, they're not the same. They're not the same source. And I would say the same thing about this. So why do we take our experience to be evidence of how things work? I don't know why. It's an interesting question, but it is naive realism. It's naive realism in the sense that your experience doesn't reveal to you how many things work. And all science, all scientific progress is a slow march. Away from naive realism. And the same has to be true for neuroscience and the brain. So let's go deeper into this idea that the brain is not a reacting machine. What are the threads of evidence? Well, I think first of all, if you look at how a brain is structured, okay, so let's just go back to primary vision. I think this is a really good example. And I should say, I just published a paper that summarizes a lot of this evidence in one place that was, I published with Earl Miller from MIT in Nature Reviews Neuroscience. And most of this is not my own work. This is, you know, me summarizing with Earl other people's work and also some of his electrophysiological work. We'll link to that paper in the show notes. Yeah. But so let's just take V1. I think this is, this is really interesting. So if you look at the synapses, so what, so primary visual cortex is called primary visual cortex because fibers from the retina pass, basically they, they run along the optic nerve, they pass, some of them will terminate in a subcortical area called the superior colliculus, but most of them proceed. They proceed to the thalamus and then to V1, to primary visual cortex. The assumption is that those signals are what drive the neural activity in V1, drive those neurons to, to activate, to, to have action potentials, to, to produce electrochemical changes, except that 95% of the synapses in V1 neurons come from other places in the brain and not from the brain. They come from the thalamus. Other places, like other cortical areas and not from the thalamus. so most of the signals are not bottom up from the retina to the brain they are from the brain to other parts of the brain they're top down that's one interesting piece of evidence so just to make sure i understand it the visual cortex is getting most of its input not from the optic nerve but from other areas of the brain that presumably are not receiving light where are those areas and what type of data are being transmitted here's one example so i'll just say you know like trigger warning if anyone is unhappy or upset by discussions or descriptions of studies that harm animals you know they might not want to listen to this because it's kind of a problem for them to listen to this because it's kind of a problem for them to listen kind of a brutal experiment. But there was an experiment done where they took mice, I think it to this because it's kind of a problem for them to listen to this because it's kind of a problem was mice, it could have been rats, but I think it was mice, rodents, and they put them, they had them run on a wheel. And they recorded from all over the brain, they sunk electrodes into the rodent's brain, and they recorded the neural activity, the electrical activity in the neurons in many places, including in V1. Okay. Then they ablated the retinas of those animals. They destroyed the retinas of those animals. So no light now is getting into the brain. V1 neurons quieten down for 24 hours. And then they ramp back up to a normal level of activity. Sorry, let me make sure. But the animals are now blind. Yeah, they are. But V1 is, the recordings are back to a normal level. And what is driving those neurons? And what is the output? Well, those animals can still move around. I mean, they can smell things, they can still move around. Yeah, because you just destroyed their retina. You destroy the retina. So look, primary visual cortex is supposed to be, it's named, I mean, it's an occipital, you know, it's named as a visual cortex. That's its name. Presumably, it's supposed to be processing signals that are related to light from the retina. animals whose neurons, whose retinas have been ablated, have normal levels, normal patterns of activity in V1 after the brain adjusts. And those are related to movement. There are parts of the brain in the cortex, like, for example, and it's called anterior mid-singulates. And the mid-singulate, which does many things, but one of the things it is, visceral motor, and it's a visceral motor regulator. It regulates the viscera of the body, and it also is an association area for the skeletal motor system, and it projects directly to V1. So does this lend credence to the idea that when a person loses a sense, they have a heightened sense elsewhere? It lends credence to the idea that signals are predictive, that most of the signals in the brain are actually intrinsic signals that are predicting things. Those signals, so what's happening in that part of the, in the cingulate is neurons are projecting layer five in the cerebral cortex, layer five neurons are projecting down to the subcortical areas down to the brainstem to regulate the body. And literal copies of those, so collaterals off those axons, go to other parts of the brain as sensory predictions, which are the expected sensory consequences of those movements. What it means is that an action potential doesn't have an intrinsic meaning. Its meaning is determined by which neuron sends it and which neuron receives it. Exactly the same signal, if it's received by the spinal cord, is a motor signal. Exactly the same signal, if it's received by V1, is a sensory prediction signal. It's exactly the same signal. Its meaning, however, physically it's the same signal. Its meaning is different depending on who receives it, who sends it, and who receives it. it's relational. So what this means, I mean, for example, there are very clever studies where they take humans and they put blindfolds on them for a week. Okay. And they teach those humans to read Braille. And as they're reading Braille, V1 is, you know, going nuts. It's like definitely processing signals. And so you think, aha, but are those signals actually important for like reading Braille? Like, do they have any, you know, any kind of spatial temporal meaning? Yes, they do. Because then the experimenters, they use TMS to, they, they, they eject electromagnetic signals into the brain that disrupts V1 and their ability to read Braille is disrupted. So you've got the causal link, right? And then you, a week later, take the blindfold off. V1 goes back to mostly processing visual signals. So what I'm saying is that, first of all, that what we think of as brain regions that have very, very, very specific meanings from a psychological standpoint probably don't. They certainly have specific signal processing capacities based on their architecture and what they're connected to and so on. But a lot of the distinctions that we make, like I met a woman once who had no somatosensory system at all. Like it was just congenitally not there. But she was able to eat only by looking at herself in a mirror while she ate. So she was using visual signals to control her motor movements. Meaning if she tried to eat without a mirror, she wouldn't know how to move the spoon. No, she wouldn't. Yeah. She wouldn't know how to swallow. So sensory signals are not so that we know the world. Sensory signals are in the service of controlling motor. They're in the service of motor control. They also let us know the world, which is relevant for motor control. So I'm saying that, you know, when you start to look at the architecture of the brain, and we've only talked about architecture, we haven't talked about any of the other types of evidence yet, you start to see things differently. You start to realize, oh, well, actually, so most of the synapses are predictive synapses, and that's interesting. And that motor signals, copies of those signals are going everywhere, and they're beginning to construct experience before the sensory, other sensory signals arise. Like if this were a different format, I could show you an image, an illusion that you would experience as red. You would literally experience red and there would be no wavelengths of light in that range that were hitting your retina. But you would experience red. So you would be like predicting red, remembering red. How? Your experience of red. What do you mean how? How would you make that happen? what would you do you're saying i mean you could do that obviously by stimulating my brain in the right area is that no i don't have to stimulate your brain with electrodes i could just stimulate it another way so what you do is you you show people well i'm gonna ruin it now for everyone who hasn't seen it but you show people um a stop light like a like a traffic light red orange green except the red one where red is supposed to be is gray there's no there are no wavelengths of light there are no long wavelengths of light coming from that spot but because you've had countless numbers of statistical like there's been countless numbers of statistical regularity for you you know facing this array of signals your brain predicts that that's red and you see red you see red until i move in two gray boxes and sit them right beside and then all of a sudden the light looks gray and then i pull the boxes away and now it goes back to being red this is something i've never had i've had anyone not experienced this probably but they haven't told me i mean it's one of the best i haven't i have an illusion where i have that i got from somebody who made that where it's electrical towers are playing jump rope. So these like electrical towers are playing jump rope. It's just a video, but you can hear the towers hit the ground. You feel the vibrations in your chest. Those are all prediction signals. Prediction signals are not like abstract things. They are, it's literally your brain is using its own intrinsic signaling to change the firing of its own sensory neurons in preparation for signals that it that it expects to receive. It's acting, your act, in the world that will generate certain sensory signals, and it's expecting those signals. And when those signals come, the neurons that are already firing in a pattern to expect those incoming signals, they stop firing, and you have an experience. So the other interesting thing, this is Earl Miller's work, the only thing that's making its way from, say, V1 to the middle of your brain or the front of your brain are visual signals that the brain didn't expect, because the ones it did expect, they've already kind of canceled out the neurons, the prediction signals that were correct. So you don't react to shit in the world. Stuff in the world is there to confirm your predictions or correct them, not to react for the most part. I'm still struggling to wrap my head around this, and I now realize why you said that sometimes you're still struggling to understand your own work. Let's go from something, not to minimize the red light experiment, but let's now take that to an emotion. Okay, before we do that, why don't we take it to baseball or hockey or something like that? Like every sport, every sport would not exist if brains weren't working. We're not predictive. Like there's this really great example that's been worked out for professional baseball. I wish I had a hockey example in my pocket, Peter, but I don't. It's the, unfortunately, it's baseball. That's okay. We love, we love, we love us some baseball over here. Okay, so, you know. Hitting a baseball, presumably. Hitting a baseball, yeah. So if you look at a major league diamond, the size of a major league diamond, and you look at the speed with which a major league pitcher usually pitches at like 90, 95 miles an hour, there is absolutely no way that if a batter, if a batter waited to see the ball, he would ever be able to hit it. There's just literally not enough time. What's happening is that based on who that pitcher is, where they are, what the temperature is, what the wind is, how much he ate earlier that day, how much sleep he got, based on all of these things, based on a huge ensemble of signals, his brain is making a prediction about where that ball is going to be in a moment from now. And that is where he's going to be. He's not doing it consciously. Where do predictions come from? They come from mem- predictions are just memories. You don't, you don't experience yourself remembering anything, but basically your brain is re-implementing signal patterns from the past for the purposes of doing something in the present. That's what a prediction signal is. So every experience you have, every action you take is a combination of your remembered past and your sensory present. The sensory present is there to confirm the remembered past or to change it. And we have a special word in science for changing the remembered past. We call it learning. That's what learning is. What accounts for the differences between individuals? Why are some people better at prediction? So let's use basics. Baseball is an example because it's a very, it's a very concrete example. So what makes Shohei Ohtani or Aaron Judge better at hitting home runs? Like, presumably they're not aware of it, but is it that they saw more reps? Is it that their eyes are better at picking up the cue sooner as the, as they see the hand of the pitcher? Like, um, what do you think? So I, I don't think anyone knows the answer to that question, but certainly it has something to do with. It probably doesn't only have things. It's probably not only, um, experience, but certainly lots and lots and lots and lots of practice and repetition for sure. That's how every skill is built. Like think about exercising. So this is another example that I find really interesting. Like if you wanted to get faster at running a mile, you would run that mile over and over and over again. You would, you would train to, to do the same thing and you would do it over again as many times. As you needed to, to get to the speed that you physically could manifest basically. That means you're becoming more efficient, more metabolically efficient with practice. That's what athletes do. But what if you're, what if you're exercising to burn calories or what if you're exercising to remain healthy? Then you do something like interval training where somebody is calling out to you every 30 seconds. You don't know what they're going to say. It's changing things up every 30 seconds. That's. Much more metabolically demanding way of exercising because your brain can't predict what's coming next. So you're always adjusting, adjusting, adjusting, adjusting, learning, processing prediction errors is more metabolically expensive on all things considered than when your motor actions arise from your predictions. So every skill is built by practice. You can't become skillful at something without practice. But that doesn't mean you can't do it. That doesn't mean you can't do it. That doesn't really account for why some people need more practice than others. Like I, no matter how much practice I ever had, I will never play baseball like a professional, you know, athlete would play baseball. So I think, again, I would say the value, Peter, of, of a new theory is not that it explains everything. It's that it, it, it asks questions that were never, never been asked before. And it sets aside some questions as, you know, sometimes. Sometimes progress is asking better questions. It's not answering old questions. So I don't know the answer to your question, but what I will say is that practice, repetitive feed, you have to have practice and you have to have concrete, repetitive feedback. Practice alone without, without concrete, repetitive feedback is not usually useful for building a skill. And this is also true about emotion, you know, if you want to become more granular in how you experience the world or how you experience other people, you can learn to do that, just like you would build any other skill, but it requires feedback. And that feedback is very hard to get in an unambiguous way. Who gives you unambiguous feedback? Maybe your spouse, maybe your mother, maybe not. Maybe your therapist, if they're good and you pay them enough, you know, it's the, it's not like, you know, building other skills where there's concrete, unambiguous feedback to be had, but it is, it is a skill. It's a skill like any other skill that can be built. And that's, I think the thing that why people find this theory really valuable. They find it valuable because it gives them agency where they didn't think they had any and it gives them hope. So, so how do we, how do we transition to that? So there, there are, if you look at certain, certain areas of cognitive behavioral therapy, for example, we'll talk about the relationship between thought and emotion and action. And I think those are attempts to also give, give agency, right? So. Really? I think so. Only just say that the, the treatment strategies work, but they don't work for the reasons that cognitive behavioral therapists say they work. They couldn't, they couldn't possibly work for that reason. So that's, that's. That's kind of where we're, let's go there. Cause that's kind of what I was trying to understand is how does this explain an observation of CBT or DBT's effectiveness? Well, I think first of all, I mean, have you ever tried to not think a thought? Well, it's impossible. We know that. Yeah. It's really hard. Yeah. Yeah. However, if you change your actions or you change your circumstance, like you get up, go for a walk, or you don't even have to physically move, you can just virtually like move. Meaning like change your attention. Yeah. Yeah. Just shift, actually move your eyes. You could, you don't have to move your, the rest of your body. You can just move your eyes, shift your attention to something else. That works sometimes. So what I would say is that. So, but let's, let's pull on that thread. So let's use the DBT example of opposite action. This is one of my favorite personal techniques, right? When I am really upset, I, I a hundred percent isolate. This is my default pattern when I am upset. I want to pull myself away from everything and everyone, including my family. So cognitively, I know this is not a good thing to do, but I do it. And when I'm, when I'm able to, I can muster the energy to undergo opposite action. So I will say, I'm really stressed out. I'm really angry. I'm really upset. I'm going to isolate myself here. No, Peter, get up off this chair and go and play baseball with your son or go and play soccer. And it guarantees you're going to. Feel better, but it's like, it's so hard to get up and do it. So for sure, but I do feel better. So why explain everything that's happening through the theory? Well, I can't explain everything, but what I can say is that every mental event begins as a motor plan. Every set of predictions begins as a motor plan. The remembered past begins as a motor plan, a plan for. You know, an allostatic plan for your brain is anticipating the needs of the body and attempting to meet those needs before they arise. It's a plan for your heart and your lungs to coordinate and your gut to coordinate. It's a metabolic plan that will support the skeletal motor plan, whatever it is you're going to do. And copies of those signals become your thoughts. They create your thoughts. They create your feelings. They create your sensations. So the reason, or a reason, or maybe a part of the reason why literally physically doing something different works to change your thoughts and feelings is because thoughts and feelings are the result from motor, the preparation for motor movement, not the other way around. And actually, if I were going to be. Sorry, say that again. It's not that you see something, then you think about it, then you feel something, then you move. Ah, yes. Yeah. It's that you start with a movement. You start, right, if we were to stop time right now, what's happening is your brain has some, there's some pattern of signals of what just happened, and it's making a set of motor predictions. So it's starting, it's preparing to change what's going on in your viscera, in your metabolism, the coordination of that. It's preparing to send signals. And it's also preparing to receive signals that it expects to receive based on those motor changes. That's, it's, you start with a motor plan, then you think and feel. Actually, I would say then you feel and think, and then you see. Or maybe seeing happens at the same time as feeling and thinking. But basically, it's motor first, mental second. It's not mental first, motor second. That's, we experience the world that way. That is not how it works under the hood. And it can't work that way. I mean, there's a beautiful book that was published by a couple of physiologists called the, was it called The Principles? No. What was it called? We're going to find it. We're going to put it in the show notes. It'll come to me. Yep. This book is like, this is a, this is a masterpiece. This book is a masterpiece. Yeah. It's a masterpiece. Because they basically, I think they go over a fly, a mouse and a primate, maybe. No, maybe it's a fly, a worm. And I don't know, they take three organisms and they go over basically like the, the energetic constraints on a nervous system. And they just show that if it didn't work by prediction, it couldn't possibly work. The Principles of Brain. Do you think this explains, by the way, why our brains, you know, the famous statistic, right? It's 2% of our body weight and yet 20 to 25% of our metabolic demand. Is, is that in your mind a further line of, of contribution to this? Um, I don't know. Principles of Neural Design. It's called The Principles of Neural Design. I don't know. I don't, I certainly haven't ever treated that as evidence before. And also I would say the estimate that your brain takes 20% of your energy budget is based on the full cellular respiration cycle. So it includes oxidative phosphorylation. And the brain, neurons don't always get ATP by the whole cycle. They sometimes, some neurons almost exclusively get their ATP by glycolysis, but that doesn't require oxygen. So I think it's just more complicated. I think it's a good case that the brain is a very, it is your most expensive organ. So, so now let's, let's think about that through the lens of other animals, other mammals even. Would you agree with the statement that we as humans have the most developed brains relative to others? No. No. No, no. So, I mean, our brains are not more developed. Our brains are differently developed. You know, our brains are, we have exactly. We, the size of a, you know, our cerebral cortex are not like larger than what you would expect for a primate of our size. I mean, primates have a larger, larger proportion of the cerebral, larger proportion of the brain is the cerebral cortex than for other, for some other mammals. But that's a, that's an innovation that comes with primates. It's not like human specific. And there are other animals that have much larger cerebral cortexes than we do. elephant, right? Or a whale. So what is unique neurobiologically about humans relative to others? Yeah. So I think one thing that's unique is, it's probably not the only thing, but one thing that's unique is our capacity for abstraction. And that you can see the evidence for, or what, maybe not evidence, but the like anatomical substrate for that you can see. So if you were to take the cerebral cortex off the rest of the brain and lay it out flat like a napkin, what you would see is that there's an architectural gradient there. And the architectural gradient is mostly in the upper layers. And it kind of looks like this, that like when you're at V1, so you have like at the outer part, you have V1, A1, so primary visual cortex, primary auditory cortex, primary somatosensory cortex. Sort of. And there the neurons are very small. And they have fewer connections to each other. So there are a lot of neurons, but they're very tiny. I'm talking about pyramidal neurons mostly. And they're not very well connected. So they're processing small details. And at the other end of the gradient, you know, in the midline, in the areas that are closest to the subcortex, which we would call limbic, there are fewer neurons, but they're honking big. And they have a ton of connections. So the thickness of the cortex is the same, but the constitution of the architecture is different. You go from a lot of little cells to fewer, to fewer, to fewer, to fewest. Okay. There's also a temporal gradient, but we would call that dimensionality reduction or compression. So the signals are being compressed, or you could say they're being decompressed. So what is unique about a human brain, or not unique, but what is special about a human brain is that our ability to compress is greater. We have a lot more, that gradient is sharper in a human than it is in any other animal, even our closest relatives, like a chimp or a gorilla. Because what it lets us do is it lets us see similarity in differences. It lets us treat, you know, a cup and, and, um, a ladle, a pail and a, and a, and your hand as something to drink out of. It lets us see a kitty cat and a tiger and a cool guy, all as cats. It lets us, right? So, uh, what a chimp or what a, what a chimp can do is a chimp can probably, a chimp can probably understand that a monkey climbing a tree and a snake climbing a tree is both climbing. They're both to climb. And it might even understand like a human climbing, like literally climbing up the stairs is the same as climbing. Whereas I think probably a macaque can't do that. They probably climbing a stair, 10 stairs and climbing a tree would be seen as different actions, but I'm guessing, I don't actually know. I'm just sort of inferring, but what it definitely can't do, is understand a metaphorical social ladder. Whereas a human can understand that. So a human can find functional differences in things that look different, smell different, sound different. This is something that humans can do. Now, on the other hand, here's something humans can't do that a chimp can do really well. If you're, do you ever have problems trying to find your keys? Chimp would never lose its keys. Like chimps forage for, they forage for food. So their ability, their, what we would call episodic detail, their ability to remember detail far outstrips a human's ability to remember the details. So, you know, we would get lost in the forest, whereas a chimp would not get lost. They would know exactly where they were by fine grain details that we would probably ignore, which is also a consequence of our great capacity to abstract. And what comes out of this great capacity to abstract? Invention. Civilization comes out of it. I mean, like basically there are many, many, many things that exist because humans collectively, we impose functions on things that they don't have by their physical nature. But if we impose them collectively and they dictate our actions, then they do have those functions. I want to go back to this idea of chronic stress, right? Because at the end of the day, what I think matters is our experience, our subjective experience. I mean, we've already touched on the idea that I think we both both believe, which is the state of one's mind can impact one's health or vice versa. I shouldn't infer the causality like that, but let's just say that there is a relationship between the state of mind and the state of health. And by the way, even if there wasn't, why would we want to suffer? Right? Why would we want to suffer in our, as David Foster Wallace calls it, the tiny little skull-sized kingdoms on our shoulders, right? Like why? We don't want to suffer. Yeah. So I think there are a couple of things that I would, a couple of caveats that I would make. First of all, there's a difference between discomfort and suffering. I can think of lots of reasons why I would deliberately engage in discomfort. Yeah, exercise. Do it every goddamn morning. Yeah, exactly. Exactly. Exactly. Or, you know, I don't know, learning to play piano or learning, doing a PhD or whatever. There are lots of reasons. Getting your kid out of bed in the morning. Morning when they don't want to. For sure. Suffering though, I think is a different matter. Suffering is, there's something additional to suffering than over and above discomfort. And in fact, in chronic pain, the goal is often to reduce suffering, even to dissolve it into just mere discomfort. So that's the first point that I want to make. The second point that I want to make is that you can talk about stress. So what, I mean, you can talk about stress from a metabolic standpoint, or you could talk about stress from, from a subjective standpoint. And, and I think it's important. But the metabolic standpoint is difficult, Lisa. So for example, like I can, if I, if I had 10 people lined up and I measured free cortisol levels in all of them and epinephrine. Yeah, but I just want to make the point for the listener as well. If I measure all the catecholamines and all the adrenocorticoids, the stress hormones, it tells me nothing about what they're experiencing. Okay. So cortisol is not a stress hormone. It's not a stress hormone. Cortisol, as you know, is a glucocorticoid. It's involved in glucose metabolism. That should be a clue. Like if you, when you, when you wake up in the morning and you go to drag your ass out of bed, you're, you have a cortisol surge. Why? Because you're about to do something that costs energy. So that should, to me, that was a clue. Like when I realized, you know, somehow, I was talking about it until 2010, when I was at a meeting at NCI, National Cancer Institute, and they were talking about glucocorticoid metabolism. And I was like, holy shit, depression, depression, major depression has, people have cortisol dysregulation. It's just a hormone that is involved in regulating glucose metabolism. That means that stress probably has something to do with glucose metabolism. Glucose metabolism. So when I thought about it more and over the years, this is what we've come to. Really, a moment of stress, metabolically speaking, is just whenever your brain is predicting there's going to be a big metabolic outlay. Allostasis. Your brain is anticipating the needs of the body and preparing to meet those needs before it arises. By the way, Lisa, you've used the term before, and I know what it means, but I want you to contrast homeostasis and allostasis because we talk on this podcast a lot about homeostasis, which is the reaction. Reaction too, but maybe you can put that in context. Yeah, yeah, sure, sure. So homeostasis is reactive. Allostasis is predictive. Homeostasis is about returning to a set point or a range of set points. Allostasis is not about returning to any set point. It's about efficiency. It's about metabolic efficiency. So I can be, well, someone could be in allostasis when they're running a mile and when they're asleep. I mean, I wouldn't be in allostasis when I'm running a mile, but somebody could be, but they would never, nobody would ever be able to maintain allostasis when they're running a marathon. That's just too much of a disruption. So allostasis is predictive. Homeostasis is reactive. Allostasis is about maintaining balance or efficiency. Metabolically speaking, it's not about trying to reduce costs by getting back to a set point. Different systems can work by homeostasis, but they are all coordinated by the brain's allostatic efforts. And there are, you know, global metabolic signals that the brain receives. GDF-15, there's some indication cortisol actually may function this way. There are a number of kind of general signals. I think even lactate probably classifies as one. Yep, yep. It's possible. So I'm talking about. Allostasis because I'm talking about prediction. So when the brain is predicting an allostatic disruption, it's anticipating the needs of the body and preparing to meet those needs. That actually is the definition of allostasis, according to Peter Sterling, that we use in our lab. That is stress. I mean, that's stress. That's when you see a cortisol surge. That's when you see other chemicals and so on. We don't always feel subjectively, distressed when there is a moment of stress. Correct. Right. It could be heightened. It could be pleasant, as you said. But when there's. And as long as you replenish what you spend and you're predicting well, and you're not like, you know, swimming in a sea of uncertainty where you can't predict very well. By definition, that's what it means to be uncertain. You can't predict. You are, you know, what you spend, metabolically speaking, and now I'm kind of like veering into metaphor here. What you spend, you replenish what you spend and you're okay. But if you don't replenish what you spend or you mispredict or you are in a sea of uncertainty or you have costs that can't really be recovered. Like maybe you have systemic inflammation for some reason. Like anything which is basically going to metaphorically make withdrawals from your metabolic budget, that will very slowly could accumulate over time and then you will be distressed. Because fundamentally, mood is related to metabolic status. Okay. Let's take another example of a child that is being abused. So there's two things that I can at least imagine that are creating distress. The first is the unpredictability that you said. I don't know which day dad's going to come home drunk. And I don't know what he's going to do when he's going to hit me or when he's going to hit mom. And then there's a second feeling that I think is related, but I'd like you to comment on, which is the helplessness of the situation, which is I don't have agency in this situation to do anything when dad comes home drunk. So that's, there's, there's uncertainty. And then even when something's happening, I don't have agency. And to me, I can't imagine a greater set of circumstances to produce distress in anyone. I, even though I use a very pointed example with a child. Yeah. I would say though, that there's an additional thing there that there's an additional, so there's uncertainty, but there's also, and there's lack of agency, but there's also, you know, we're social animals. So we don't manage our, our nervous systems on our own. We, we are the caretakers of each other's nervous systems under best circumstances, right? The best thing for your nervous system, Peter, is another human. And the worst thing for your nervous system is also another human. And so one of the things that we do for our children when things work well is we, we maintain allostasis for them. They can't do it. Their brains actually aren't equipped to do it. They have to kind of learn. They don't know. I mean, a baby is born. It can't even nurse. You have to teach a baby how to nurse. A baby can't even control its limbs. I mean, babies, the, the wiring is there, but it's not fully developed. Partly what we do when we feed them and clothe, that keep, that regulate their temperature and cuddle them and do all these things is we're actually regulating their, their nervous system. We're regulating their metabolism and slowly, slowly, they learn to take this on themselves, but not completely. We regulate each other all the time. So we can basically create for each other savings and like to use that meta body budgeting metaphor, like your brain's running a budget for your body. It's not budgeting water. I mean, it's not budgeting money. It's budgeting salt and glucose and whatever. You know, this is a metaphor that I've used before. It's a metaphor. So it's not an explanation. It's just a metaphor, but it's a good metaphor for this. Yeah. We can create savings for each other. We, we regulate each other. We literally regulate each other. You know, there was, you know, you have your hand up here like this. And so, you know, if you and I were in a coffee shop, I might do this and then, you know, you might scratch your head and then I might like push my hair back. People coordinate their actions. They coordinate their breathing. They coordinate their movements and you coordinate your breathing. You will, you know, more likely coordinate your heart rates. This is something people do when they trust each other, when they like each other. Right. Yeah. We can also disrupt each other. Right. So one of the things that's happening for a little kid who's in an abusive situation is that they're not getting the benefit of that kind of savings that most of us who are in safe environments, you know, benefit from. How does that translate to the to the metabolic deficit? Right. So in that situation, it doesn't it doesn't it just means everything. Everything is costing more. Like literally, if you are with a friend and you have like a backpack full of rocks on your back, like an experiment, you're with someone that you like and that you trust. You burn fewer calories when you schlep that thing up a hill than if you're by yourself or with a stranger. So what this means is it just means that like things are more expensive. That means that that kid's going to just metabolically be less resilient. Plus, if you add to that the fact that they're going to be more vigilant. And there's actual harm being done to them. It's like a perfect storm of metabolic burden that doesn't show up necessarily. Then it shows up in adolescence or in adulthood. And it doesn't just show up as mood disturbance or whatever behavioral problems. It shows up as like diabetes, likely increased likelihood of a metabolic illness, diabetes, heart disease. I mean, ACE, you know, ACE scores is like, you know, like the adversity in childhood. Predicts. Not perfectly, but bad health outcomes, bad health outcomes. So it's like a slow drip on a pipe. One drip is not going to do anything. You know, a hundred drips, not going to necessarily do anything. But eventually, if it goes on for long enough, that drip will bore a hole in a steel pipe. And or, you know, monkeys jumping on a bed or whatever, you know, like eventually the bed will break. Maybe not the first time, maybe not with the 10th monkey, maybe not with the 20th monkey, but eventually it will break. And so I think that's the way to think about it, that it's a slow, slow process. So chronic stress might make you feel like shit, but it's not actually going to harm your health immediately, but it will inevitably harm your health eventually. So what, how do we turn that into a prescription? So let's, let's just now. You know, talk about a situation where uncertainty and helplessness take a different form. It's no longer something as dangerous as an abusive parent. It's uncertainty about a job. It's uncertainty about a relationship. It's uncertainty about the world we live in. AI, you pick, you know, we could all come up with many things to be uncertain about and to also have some degree of helplessness about that certainly would never rise to the level of trauma or traumatic insult. And yet two entirely different people can be faced with the same set of external circumstances and have a totally different manifestation of this notion of chronic stress. So one, I'd like to understand a little bit why that's the case. And perhaps more importantly, what can the person who is having a more negative response to that do in order to shift the balance and take that metabolic cost off their shoulders? Well, the first thing I would say is that I don't think we have to imagine what it's like to live in uncertainty. I think, I think modern life is designed to bankrupt a human body budget. And we're not equally all affected by these things, but we're all affected in one way or the other. And even people who think that they are immune are not immune. Right. So in the popular press, you see people talking about, you know, fight and flight circuits and how they're overworked. And that's why everyone's so stressed. There are no fight or flight circuits in your brain. You don't have fight or flight circuits in your brain. Your periaqueductal gray doesn't contain fight or flight circuits. It contains circuits for regulating your autonomic nervous system. And it regulates your autonomic nervous system throughout your entire life. And of course, during moments of threat, it's very active. But we have done these experiments where we have people do a memory test where they have to remember. One thing that modulates the periaqueductal gray, the so-called fight and flight circuits, too. You know, it's like the task is easier than remembering a phone number. There's no stress involved in the conventional distress sense. But yet you see these circuits being active. So I would say there's tremendous amounts of uncertainty combined with the fact that our niche is much bigger, like the things that concern us, that affect us. Our metabolism is much bigger than it used to be because of the news and because of the Internet and so on and so forth. So we've got expanded niches, like an expanded potential burden, expanded uncertainty. So a lot of expanded cost. And so people are more vulnerable to metabolic illnesses of all sort. And my prediction would be, you know, I hate making predictions, but I will predict this because I won't be alive to see the result. But I think in 100 years. If we still exist as a species, somebody's going to look back at this time and just see it as a massive public health crisis, right? Where we're basically all bankrupting our body budgets at the same time as we don't sleep enough and we eat pseudo foods, you know, like anything that's not on the periphery of a supermarket, you know, and we're doing all these things, each of which is sometimes a nudge and sometimes a massive shove in a particular way. So that I feel very comfortable making that prediction. Your question about like, well, why are some people more susceptible? Like, you know, I mean, trauma. Why do some have more equanimity? Adversity is the potential for something negative to, you know, but there are people who experience adversity and who are not stressed and they're like subjectively. And there are people who experience stress. They're experiencing things as adverse that like the mythical average person wouldn't. All I can say there is it has something to do with prediction and memory. I think that seems pretty clear. And also remember that, you know, you're. I don't have to tell you this. I mean, you know this, that while there is no muscle memory, really, I mean, in the sense that your muscles don't have a memory, your brain has a memory, you know, nervous systems do adjust themselves. To the environment that they're in. I mean, your brain wires itself to its world. That world includes the body. From your brain's perspective, your body is part of its world. It's like a really important part. It's not just what's out there. It's also anything that it doesn't have direct access to. And. That. A brain wires itself to the body. So if there is chronic stress. Or if there's adversity. And the brain's regulation of the body. Changes how the body is. The body then sends signals back to the brain that the brain then has to adjust to. Right. So what I'm trying to say is that you, Peter, have a brain that is wired. To see out of your eyes. That are literally in the positions they are. If we magically took your brain and stuck it in somebody else's skull. You wouldn't be able to see. Right. If somebody. Something happens to somebody's ear. Right. They can't hear for a while. They have to like adjust. I mean, think of it like. When you get your teeth fixed. And then your tongue is like constantly probing at the. You know, it's because it's trying to forage. It's learning. And it will wire itself eventually to whatever is new and different. If you have an illness. It will wire itself to whatever is new and different. And then it will wire itself to whatever is new and different. That's a metabolic burden right there. Just the healing. Right. That means the brain doesn't have necessarily the resources that it needs. So that when those signals disappear. The brain is still predicting that it's going to receive them. Because it's not updating. It's not learning. Because learning is expensive. That's chronic pain. That's pain that is not. Pain is real. But the tissue damage is gone. But you don't feel pain in your body. You feel pain in your brain. You feel everything in your brain. You see in your brain. You hear in your brain. All of your sensations are in your brain. You know, you pinch yourself. You don't feel it here. You feel it here. So I think that one source of individual difference. Is you have an adaptable nervous system. You have an adaptable body. You have an adaptable immune system. That means it learns. And each of us come to these external circumstances. With different learning histories. That means we're wired. I mean we are wired by our experiences. Not, I mean, it's not, I'm not saying that we're blank slates or anything like that. But people come to. To a situation prepared to experience it in a particular way. Everything you experience. Everything you do. is a combination of the remembered past and the sensory present. If you don't have a remembered past and your brain can't cobble together bits and pieces of the past to make a prediction, you will be experientially blind in the moment. You just won't, it's just be noise to you. But how do we change that? So let's, everything you're saying makes sense. And if I'm in a situation where I am just manifesting, I'm just making up this example. I just, I get so anxious under a certain circumstance that you wouldn't get upset about because you bring a different history, a different memory, a different pattern, a different recognition to that system. But I bring this very negative experience and I have good reason to because of whatever happened in the past. But now I want to change that. I don't want that to be my problem. I don't want that to be my experience anymore. What can I do? Yep. So one thing that you could try to do, which won't be very effective, is you could try to reach back into your past and change your past. Because who are you right now? You're a combination of your remembered past and your sensory present. So one way to change your current experience is to change your past. Well, good luck with that. That's a little bit. Sorry, but Sir Lisa, change my past or change my interpretation of my past? Those are two different things, obviously. They actually aren't different. Exactly. When you remember your past, it is a current experience. Memory isn't different from a perception. Okay? Like when you're remembering something, it is a current experience that you are having of something that happened in the past. But it's not identical. And it's actually. Yeah, I sort of. Maybe I didn't say this correctly. What I mean is you could change your interpretation of it, couldn't you? Yes, you can. But the more effective thing. Well, anyways, that's where I was going. Where I was going with this was to say you could try to change the meaning of what happened to you in the past, which some psychotherapies attempt to do, and with more or less success. But one thing that you could do is you could change. You could change something now and practice that change so that you could predict differently in the future. It's like driving. You invest energy. You invest energy in the moment to learn something new. And you practice and practice and practice. And then what starts off being deliberate ends up being automatic. Every skill works that way. Driving works that way. So, for example, when you are feeling overwhelmed and you have to force yourself to go play soccer with your kid or whatever, you could practice that skill in advance before the heat of the moment so that in the heat of the moment, your brain is predicting differently. So, let me just put it this way. I don't know what you did in Canada when you lived there. One thing I used to do was the first snowfall, first. It's not really a snowfall. It was like the first ice that appeared. I would get into my car and I would. I'd go to a side street or a parking lot and I'd deliberately put myself into a tailspin so that I could remember how to get out of it. I didn't want the first memory to be the time when I really needed it. I wanted to practice. Sometimes you can take advantage of moments where you can practice actually making meaning differently. So, here's an example I often use. I have a colleague who studies positive emotion and like the benefits of positive emotion. And I'm an inherently skeptical person. So, I thought, well, I'm going to try it myself. So, I thought, all right, I'm going to experience awe every day. I'm going to like give myself a little exercise. And so, I started with something easy. Like I would drive along. I lived in Boston at the time. I'd drive along the pike, Massachusetts Turnpike. There was like a billboard of a cute little baby orangutan with its mother. Adorable, adorable little baby. So, I would look at the baby as we were passing by it and I would think about the baby and I would have a moment of awe. And then I moved on to things. Like, you know, the sound of the waves, you know, beautiful flowers, the crickets at night, you know, really loud crickets at night. And then eventually that became easy. So, then I started to try like, well, how about a weed? Or how about a weed popping out of a cracked sidewalk? A weed, a dandelion poking its ugly little head out of a cracked sidewalk can be a moment of awe if you understand it as nature's power to be unconstrained by human attempts to control it. Now, it's very easy for me to experience a moment of awe when I most need a break. Like, when my nervous system most needs a break. For example, I'm about to take an important meeting. I'm stuck in traffic. I'm about to take an important meeting on Zoom and my computer fails. Or, you know, a meeting where I really can't lose my temper, you know, where I really have to be cool. Or, you know, a time when, you know, I'm sleep deprived and my, you know, little kid is doing something to drive me batshit crazy. You know, these are all moments where if I can just get up and go to bed, I'm going to be able to sleep. And I'm going to get a little distance for two seconds. I can take a breath, metaphorically speaking, and then I can come back into the fray. And what are you doing? Are you picturing the dandelion? Are you going back to just a broad. No, I'm finding a moment. Like, for example, if our internet failed right now, and I would, as I often do, I would be like, well, it's miraculous that we can even talk to each other. I don't know where you are, Peter. I'm imagining you're on the West Coast. I'm on the East Coast. That means. No, you're not. Okay. Well, wherever you are. The point being that we could be thousands of miles away from each other. And, but we're talking to each other like we were in the same room. So yeah, when it fails, it's frustrating. But the fact that we even get to do it is like amazing and awe-inspiring. So no, I find something in the moment to be in awe about, you know? And how long did that take? Well, I'm giving. The practice. No, no, this is a very important example and I really like it. How many weeks or months did it take to re-watch? It took a couple of months. It took a couple of months of daily practice. The thing I would say about having more control and more agency is that, first of all, it doesn't look the way you expect it to look. You expect, you know, you expect to be able to just in the moment do it. You can't. It requires practice. Like I was just telling somebody yesterday, you know, like who wants to just stand up and give a lecture. I'm like, yeah, I can stand up and give a lecture after I've It looks like I'm talking off the cuff. And I am in that moment. But it's all automated. I've practiced it already a ton of times. So you can take advantage of that. The control is looks different than you expect. It's harder to get than you expect. And not everybody has the same opportunities as everybody else. So some people have more options for controlling and for changing things. But even a monk who is being tortured can do it. That means that we all, all of us, even in the most dire moments, we all have a little, a smidge more control over how we experience ourselves in the world than we think we do. And in some moments, all you really need is that little smidge. You know, in some moments, it's that's good enough. And in other moments, when you have a little bit more energy, you know, you can practice lots of different, you practice basically making meaning differently. You practice. So for example, I, every morning, I get up and I have to walk by my office to get to the gym. And the temptation is so always there. I'll just look for a minute. I'll start looking at my email. I'm going to be there for an hour. Right. But every morning I am practicing not doing the thing that I feel compelled to do in order to do the thing that I know later, I will be glad that I did. That is, you know, in the, in the moment it's trivial, but the practice in being able to do it. And you think everyone is capable of that? I think everyone is capable of that. I think everyone is capable of something like that. So what, I'm not disagreeing with you. I'm not agreeing or disagreeing with you, but I want to know what you would say to the person who's listening to us who doesn't, cause you and I, I think are both cut from that same cloth, Lisa. I've always chalked it up to, well, I, yeah, let's just say this. So someone's listening to us and they're saying, I don't have that gene, Lisa. I, I don't have the willpower. And how would you correct them in their thinking? Well, here's what I would say. First of all, no willpower is, this is just. based on empirical evidence, like how do you build a skill? It has nothing to do with willpower. Willpower is putting a bowl of potato chips in front of yourself and trying not to eat it. What I'm talking about is getting rid of that, like you construct your niche so that you don't have to deal with the bowl of potato chips. If you want to change how you feel in the moment, you can either change your remembered past, you can change your sensory present, or you can move in some way, which usually involves changing your sensory present. But like, that's pretty much it. But what I guess, in the end, I'm a scientist. And what I would say is the following. I have emails from like, I have received more in excess of like 10,000 emails from people who have read both of my books and have found ways that neither of those books gives people advice on how to use these scientific findings in their own life. But they do. These people write to me with stories about their own lives and how they've used it and how hopeful, how it gave them a sense of agency and a sense of hope. I've had people write to me from, from a battlefield, like on a battlefield, like, in the middle of a war. I've had people who've written to me, like all walks of life, all kinds of people. And I will also say that I, we used, I mean, how I came to any of this, right? How I came to any of this. I mean, I study emotion and I had a lot to say about emotion and the brain and so on and so forth. But all of the work on metabolism and meaning making and all of that came later. Any of the people who have written to you used any of what you've, you've, you've written about through the lens of grief. So you talked about your personal experience where you have a much better capacity to manage your emotions in distressful situations. And part of it is making sense of it, finding awe in, Hey, like I know the internet went down, but the fact that we have internet's amazing. But now when, when someone loses their child, loses their spouse, I mean, it's a, it's, it's, it's grief to the highest extent. Is, is there, tell me, tell me how you, you think about reducing suffering in that state? Yeah. So I think that when I'm talking about the brain's meaning making capacities, I'm not talking about grand things like finding the meaning of life or explaining why someone dies or things like that of a teleological nature. I'm talking about things like. What does a set of sensory signals mean? So the thing about grief, the thing about losing someone that you love is that you are losing a source of body budgeting impact. Like we regulate each other's nervous systems. My daughter, when she, when she was a baby was regulating my nervous system as much as I was regulating hers, maybe more. And when you lose someone you love, it can feel like you're losing someone. And I think that's a really good point. It can feel like you've lost a part of yourself and you have, you've lost body budgeting support. You've lost somebody that you are physically connected to in some way. That's what love and safety is. If you feel safe with someone or you make someone feel safe, you create an environment for them to feel safe. You are physically linked to that person in a way that is not necessarily metaphorical, really, in that they had an impact on your mental health. And that's a really good metabolism and you have an impact on theirs. I have a friend, I can text her. She lives in Belgium. I can text her three little words. She doesn't have to see my face. She doesn't have to hear my voice. What I text her will affect her heart rate. It will affect her breathing rate. It will affect her mood, right? I mean, powerful words and actions in relation to other people are powerful. So you, when you lose someone, you've lost that and you feel it. Now that doesn't explain why they died. It doesn't make it seem any more fair that they died, but it does help you understand what those sensations mean and that they eventually will in like, I would say the evidence is something like 70% of people who don't experience complicated grief will feel it. And I think that's a really important thing. You know, they will go away. In what period of time? Well, I think I'm thinking of George Bonanno's work now. And you're now your cat. I mean, I haven't looked at this work for a long time, but I think it's like a couple of months and then complicated grief, like loss of a child or something can go on for, for longer. But eventually within a year or two, I think the evidence is that people, if it, even if it takes a long time, it takes that long. It's not that they're not sad. It's that they're not suffering. Right. So it'll still feel like shit occasionally over time, but, or maybe every day, but you won't suffer. It'll be discomfort. And are there things that an individual can do to shorten that period of time between suffering and sadness? Yeah. Well, the evidence suggests that you can remember times that, um, were, were happy. So the people who recover faster from, um, the loss of a loved one are people who remember the positive, meaningful time together. That's what the evidence shows. And it's interesting because if you think about, there are cultural, like, traditions that get you to do that, like setting Shiva in a Jewish, when you're mourning someone Jewish, or, you know, that you're awake or, you know, that you're remembering things often with other people that bring the person, make the person closer to you and bring them more alive. Like, so here, you know, so here's an example. This is a negative example, but I think it's an interesting example. So my daughter doesn't remember herself when she was two. Of course, like who does, right? I remember her when she was two and my husband remembers her when she was two. And we had, we have a shared memory of her when she was two. She doesn't remember. So that means I had a relationship with someone who's not here anymore. And sometimes, Peter, I miss, I mean, I love my kid to, I love her to bits, but I sometimes miss that exuberant little two-year-old. Like I really do. And it's not. First, I just, I want to pause it for a second, because this is so funny that you bring this up, Lisa. Two nights ago at dinner. We sat at the table, me and my wife and our three kids. So, uh, nine, 12 and 18. And we all run around the table explaining our first memory in life. So what is the first thing each of us remembered? And it, for all of us, it took place at around three years old. Now, of course, it's much more, I'm less interested in what me and my wife experienced, but I loved hearing what the kids experienced because I, to your point, like I was there, I was witnessing it. And there's amazing things they can't remember. Like the fact that my daughter doesn't remember the first two houses she lived in. No recollection at all. Right. But what you said is so profound that I never thought about it that way, which is, um, my kids get so annoyed with me because I can't stop telling them about how much I adore them. And I'm like, when you were little, you were the cutest, sweetest, most edible thing on the planet. And they're like, dad, shut up. But what I'm missing, I think, is that was, they don't remember that. They don't know what I'm talking about. They don't remember that. But your wife remembers. Yeah. And so what I'm saying is that, you know. And we text each other pictures and videos all day long. Right. No, we do that too. Yeah. We do that too. And my husband was so great, you know, when, when our daughter was small, he would always like write down these like perfect little gems of things that she would say. Like, we have a journal, each of them, we have a journal for all the funny things they said. Yeah, exactly. And so, you know, we'll text each other things like just in the middle of the day. But the point is that I can experience that feeling again with him, the two of us together, not with her. That's such an interesting observation. She's not there in that capacity, but you're still experiencing her. Yeah. And, you know, being her mom was, is a huge part of my life. And we're very close. And I've, you know, we're very close. And we, we talk to each other, like text, you know, like all the time. And, you know, we don't live in the same city anymore, but, you know, like this morning we had breakfast together on Zoom and whatever. So we're close. And there's always been something to love at every age, like something new, something miraculous. But I do miss that. I do miss that little, I do miss that little girl. I, I really do. And sometimes I really, I really miss that little girl where, you know, she just wanted to be scooped up. She had to, you know, she had to be, you know, she had to be, you know, she had her hands in my hair, you know, she would be, you know, and we'd be talking to each other, like, you know, sometimes I really miss that. So, so tell me though, what is that feeling is predicting what, how do we bring this full circle to the model? Well, it's a memory. Everything is, every. This is why thinking and feeling and perceiving are not that different from each other because they all are rooted in predictions, which are memories. Predictions are memories. Predictions are your brain reinstating patterns from the past for the purposes of the present. Like when I'm reading a memoir, I'm not literally reading what's happened to someone. I'm reading how they experienced in that moment what happened to them. Their experiences in that moment of whatever happened to them in the past. When you have a memory, you're not literally remembering what happened. You're remembering your memory is creating an experience in the moment, which is informed by some set of signals from the past. And this is also, I think, a very powerful, powerful insight that you can use. Memories are not like files in a file drawer. They are not veridical. You are always reconstructing them. When you remember something, whether you have an experience of remembering or not, you are reconstructing something. You're constructing a set of signals that bears some resemblance to the past or bits and pieces of the different pasts that your brain put together. That's how it works. And sometimes when something comes to mind, like I have an intrusive thought or whatever, I'll be like, nope, not that past. Like I literally will say that out loud to myself sometimes, like, nope, not that past. It's interesting. You went into psychology thinking you were going to be a clinical psychologist. Through this series of experiments, you're unable to replicate. You completely find a new direction in your career. And yet. The. The work you've done probably has a potential for greater impact in the field of clinical psychology than you could have ever imagined or produced had you become a clinical psychologist. I'll take that. Lisa, you've given me a lot to think about, and I'm going to be I would be lying if I said I understand everything we talked about today. I think this will be one of the podcasts I have to re-listen to. I don't do that. Often, actually. But I can. I think there's going to be a few bike rides I go on just for the folks wondering. No, I'm not going to be riding outside listening to a podcast. I'll be on a trainer where I'll be. I'll be going over this again. And I'll probably come back to you with some other questions over email. So that'd be great. I really appreciate your time and your insight today as a fellow Canuck. Well, thanks for having me on your podcast. Thank you for listening to this week's episode of The Drive. Head over to PeterAttiaMD.com. forward slash show notes. If you want to dig deeper into this episode, you can also find me on YouTube, Instagram and Twitter, all with the handle PeterAttiaMD. You can also leave us a review on Apple podcasts or whatever podcast player you use. This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing or other professional health care services, including the giving of medical advice. No doctor patient relationship is formed. Thank you. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis or treatment. 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