Huberman Lab - Dr. Charan Ranganath: How to Improve Memory & Focus Using Science Protocols

Episode Date: September 30, 2024

In this episode, my guest is Dr. Charan Ranganath, Ph.D., professor of psychology and neuroscience at the University of California, Davis, and a world expert on the neuroscience of memory. We discuss how memory works, what causes diseases of dementia like Alzheimer’s, and science-based strategies to reduce age-related cognitive decline. We also cover the essential role of curiosity and the dopamine-curiosity link that can assist memory formation and neuroplasticity. We then discuss challenges with attention and focus, and how to overcome them, as well as how to manage task-switching and create home and work environments more conducive to cognitive health and longevity. Additionally, we explore the emotional aspect of memories, tools for overcoming rumination, and strategies for reframing past negative experiences. This episode will be of interest to anyone seeking to improve and maintain their cognitive health, focus, and memory across their lifespan, as well as for those struggling with ADHD. Access the full show notes for this episode at hubermanlab.com. Thank you to our sponsors AG1: https://drinkag1.com/huberman David Protein: https://davidprotein.com/huberman Levels: https://levels.link/huberman Waking Up: https://wakingup.com/huberman Function: https://functionhealth.com/huberman Timestamps 00:00:00 Dr. Charan Ranganath 00:02:06 Sponsors: David, Levels & Waking Up 00:06:48 Memory: Past, Present & Future; Sleep 00:13:23 Self, Memory & Age, Neuroplasticity 00:18:50 Tool: Curiosity & Dopamine 00:26:55 Dopamine, Forward Movement 00:33:09 Sponsor: AG1 00:34:22 Dopamine, Learning; Curiosity & Appraisal 00:40:31 Memory, Hippocampus 00:43:34 Prefrontal Cortex & Memory, Aging 00:50:07 Aging, Prefrontal Cortex & Memory; Depression, Rumination 00:58:53 Sponsor: Function 01:00:40 Tool: Lifestyle Factors, Minimizing Age-Related Cognitive Decline 01:09:39 Exercise, Brain Function; ADHD 01:17:26 Sense of Purpose, Tool: Values, Goals, Navigating ADHD 01:23:31 Forgetting, Intention vs. Attention 01:30:10 Tool: Smartphones, Task-Switching, Forgetfulness 01:36:36 Tool: Pictures, Memories, Intention 01:45:46 Deep Focus, Dopamine 01:49:36 Hearing, Vision, Oral Hygiene, Inflammation, Brain Health, Alzheimer’s 01:59:51 Déjà Vu 02:09:00 Serotonin, Reframing Memories, Trauma 02:19:05 Psychedelics, Neuroplasticity, Perspective, Group Therapy 02:27:53 Rumination, Trauma, Nostalgia, Narrative 02:30:30 Music, Pavlov’s Dogz Band 02:36:27 Zero-Cost Support, YouTube, Spotify & Apple Follow & Reviews, Sponsors, YouTube Feedback, Protocols Book, Social Media, Neural Network Newsletter Disclaimer & Disclosures

Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Charan Ranganath. Dr. Charan Ranganath is a professor of psychology

and neuroscience at the University of California Davis. He is one of the world's leading researchers in the topic of human memory. And memory, of course, is an essential component to our entire lives. Memory isn't just important for remembering things that we learn. It's also vitally important for setting the context of our entire life. Meaning only by understanding where we come from, who we were and who we are currently, can we frame what we want to do in the next moments, the next day, the next years,

and indeed for the rest of our life. This is why, for instance, that people who have deficits in memory, either due to brain damage or due to age-related cognitive decline or diseases like Alzheimer's dementia suffer so much, not just in terms of not being able to remember things for sake of daily tasks,

but also for sake of placing themselves in the larger context of their life. Recognizing family members isn't just about being able to relate to those family members on a day-to-day basis. It's also about understanding the full context of all one's memories with those people and what meaning a given interaction brings

to any of life's experiences. So today you're going to learn how memory works. You're going to learn about things like deja vu. You're going to learn ways to offset age-related cognitive decline, what the research really says about that and ways to prevent things like Alzheimer's dementia. We also talk about ADHD or Attention Deficit Hyperactivity Disorder. And Dr. Ranganath shares his own experience with ADHD, how it relates to memory and the tools that he has used in order to combat his own ADHD.

Dr. Ranganath has an exquisite ability to describe research studies in clear terms and to combine that with his own narrative and life experience in a way that really frames for you practical tools that you can apply in your daily life. Before you begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast.

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If you'd like to try the Waking Up app, please go to wakingup.com slash Huberman where you can access a free 30-day trial. Again, that's wakingup.com slash Huberman to access a free 30-day trial. And now for my discussion with Dr. Charan Ranganath. Dr. Charan Ranganath, welcome. Thank you. Speaking of memory, we go way back.

We do, we do. I was a graduate student when you were first hired as an assistant professor, which for those that aren't familiar with the academic nomenclature and trajectories, assistant professors are professors that have not yet received tenure, but now of course you're a full professor

and you are a world expert in memory, something that I think occupies the minds of all of us, even if we're not trying. So that's actually the segue to my first question, which is as we move through our day, how much of our cognition, our perception is focused on things that are happening in the present as opposed to being driven by prior memories?

Studies ever been done that evaluate how often our brain switches you know, switches to thoughts about the past. Of course we learn about things that are in our present. I know this as a cup because I was taught that at some point, but what I'm referring to is how much of our thinking on a day to day basis is literally in the past?

Well, it's interesting. I mean, it's, first of all, it's a great question to start off with, and it's interesting because I actually don't think memory is about the past. I think memory is about the present and the future. It's about taking selectively what you need from the past to make sense of the present and to project to the future. I know you're a vision guy, right?

And so if you look at people's just eye movements, right? The first time I came into this room, I'm sure I wasn't aware of it, but I'm sure my eyes were going all over the place. Now, if I came back to Visi, you say, if you're like, oh, that was an awesome interview or whatever, right? Hopefully, but maybe not. But let's say I do, right? Chances are. Yeah. So I go and my eyes will probably go right to the Rick Rubin photo. Then I'll go right to something else,

or to the espresso machine. And so my memory allows me to make predictions about where things are. And it's almost pre-conscious, so that it's happening without our awareness. And it's confirmatory. We're grabbing the important stuff and making sure everything is where it's supposed to be.

And you can see this play out in phenomena also like change blindness. It's a little bit of a different phenomena. But basically in change blindness, there's a famous example where they show a video of people playing basketball. And they're passing the ball back and forth. And then this guy in a gorilla costume just walks behind them. And about, I think it's 40% of the people who watch this video don't see the gorilla. And the reason is, is that you're generating these serious expectations about what's in front of you.

And so you're not literally seeing what's in front of you. You are creating an internal model, a simulation really of what the outside world is. And memory, whether it's semantic memory, which we'll talk about, I'm sure, your knowledge about the world, like the cup thing, if it's episodic memory, which is your memory of what happened, let's say just a minute ago, it's all coming into play in terms of your sense of where you are. If I just ask you what day is it? You will use episodic memory for that. Tomorrow morning, I'm going to wake up in a hotel room.

If I don't have episodic memory, I will freak out because I'll be like, where am I? Did I get kidnapped? Why am I here? And that's really the experience of people with memory disorders. I mean, they have to be in really familiar environments because it's frightening otherwise, right? So even I wouldn't necessarily say that we were never seeing the present. Of course we are, right? But our understanding of the present is so informed by the past that it allows us both to focus on what's important, what's non-redundant with what we already know.

And it also allows us to detect surprises and find out the things that are unexpected and grab the most informative stuff as well. Yesterday, I took a brief nap in the afternoon. I do this practice of non-sleep deep rest in the afternoon. I gotta have you teach this to me sometime. Yeah, it's very restorative

for mental and physical energy, I find. But I fell asleep toward the end of it. And when I woke up, I was in a dark room, but I didn't know where I was for about, felt like 10, 15 seconds, somewhat scary. But I had forgotten that I was in my solo studio. I had turned the room lights down. What is it when we have these lapses of memory as we emerge from sleep or sometimes

if one has been severely jet lagged, you can experience this disorientation of place? Do we know what that is? Well, a lot of your sense of where you are comes from episodic memory. Now, there's a school of thought that says that episodic memory, which is your ability to remember past events, comes from your ability to understand where you are. And we have some interesting data from sea lions, actually, that speaks to this issue. Sea lions? Sea lions, yeah. We'll get back to that. We'll get back to the sea lions. But I would argue that to remember where you are when you first get up, you have to engage in an active episodic memory retrieval. That is, you have to figure out, well, how did I get here?

And that takes a moment. Orienting yourself takes a moment. Because it's a little bit of a controlled memory search, right? It's not something that's in front of you that reminds you of where you are initially. And you're also in this little bit of a fog when you wake up. I don't know enough about sleep to say, but I would suspect that people probably are in some kind of a stage one-ish or just high alpha. These brain waves that are like very much associated with kind of

grogginess as you're getting up. Neuromodulators are probably super low. So you're, you know, so basically not much adrenaline. Yeah. Yeah, exactly. And so that's going to lead you to really be slow in doing that memory retrieval that you need to orient yourself. So like in the clinic, if you want to ask, if you want to understand whether someone

has a memory disorder, one of the simplest things is to ask them what day of the week is it? What month is it? Who's the president? Who's the president, yeah. Right now that's a loaded question. Well, it depends on what time of year relative to the election you ask, right?

Exactly, yeah. Very interesting. I'm curious also why it is that most all of us have a stable representation of who we are. So my understanding is that even people with very severe memory deficits don't wake up in the morning and wonder, who am I or who is this person in this body?

That somehow we remember that we have a self, that we are separate from other selves, that that kind of knowledge might be innate, we might be born with it, and that the representation of self in memory is very stable, is that true? Well, here's what I'll say, it's a really interesting and complex question.

Everything's, you always talk to a scientist, you get that it's complicated. But I'll give you as simple of a thing as I can, which is, so if you look at patients with amnesia, so they have a memory disorder where they can't form new memories, they have a sense of who they are, as you mentioned, right? It's not like they don't know who they are. And I mean, like, they know their names,

they know their biographies and so forth. But what happens is, at the time, And I mean, like, they know their names, they know their biographies and so forth. But what happens is, at the time, let's say if you had gone swimming and you nearly drowned, you had a hypoxia incident or a cardiac arrest or, you know, you had, like, a traumatic brain injury, severe memory deficit, right? Your sense of self doesn't update. It gets kind of stuck. And so there is kind of a sense of looking

and not expecting yourself to be as old as you used to be, as you are, because you're stuck in your sense of who you were. And I do think, I talked, my good friend, Rick Robbins at Davis is a personality psychologist, and he studies the development of personality. And it does develop, you know, it kind of stabilizes in these adolescent years and that's actually also interestingly related to memory. But it does change. People do change in really

interesting ways. So one thing is that people grow more optimistic on average as they get older. Is that right? Yeah, yeah, that's true. So Laura Carstensen, your colleague at Stanford actually has done some really cool work on that topic. They become more optimistic and yet I would argue that we become more quote unquote set in our ways because neuroplasticity, the ability to reshape our neural circuits diminishes with age.

Well, you know, so I think that's overdone a little bit. I think you're right. You know, you definitely see less dopamine activity for instance as people get older. But what I'll say is that people have gobs. If you have a healthy aging person, they have gobs of neural plasticity. But often what happens is, yeah, you get stuck in your ways and that could be related to a few things. One is that you get changes in the prefrontal cortex and that leads you to be less cognitively

flexible. It can be also because people just build up so much prior knowledge about the world that it just becomes kind of ingrained that this is the way it is and it's harder to be surprised. I mean, you kind of see this with old scientists, right? They go like, nothing's new. Everything's been discovered in 1960, and nothing new has happened since then. And by the way, for folks listening

who are considering a career in science, nothing could be further from the truth. In fact, prior to recording, you told me a saying that I've never heard before. I don't know if it's cynical or optimistic, but if I recall the quote that Dr. Ranganath passed along, which does not come from him, it descends from somebody else, not to be named,

is that, quote, science progresses one funeral at a time. Very, very actually, very interesting statement. It could be examined from a number of directions, but I agree, I agree. I mean, there's some wonderful, let's call them aged scientists with tremendous knowledge and excitement. I mean, one only has to listen to

the Nobel Prize winner, Richard Axel, talk about his lovable faction and perception, and you can sense his delight. And he's getting up there. Sorry, Richard, but it's true. He's in his seventies, right? Hopefully he'll live a very long time. And certainly science progressed as a consequence of him being alive and working on the olfactory system.

But I think what you're referring to is really important. Neuroplasticity doesn't necessarily shut down as we age. It might even stay open to the same degree as early adulthood. But if I understand what you're saying correctly, you believe that it's because people tend to seek out less new knowledge as opposed to lacking the ability to create new knowledge. I believe that's true, but that's kind of, that's an opinion.

I don't have data on that per se, but someone's probably looked at this, but that would be my sense is, is that a lot of what happens with the way people's lives play out as they get older has to do with their environment and their experience. And that's not to say that – I mean yes, neuroplasticity does change as you get older but it doesn't account for the degree to which sometimes people can get stuck and set in their ways. And you know, your example of the scientists is such a beautiful example because I look at the scientists who don't get stuck in their ways, right? And they constantly challenge their beliefs.

They surround themselves with a diverse group of people who stimulate them and they're also open to prediction error. That is they're open to saying something could be violating my knowledge of the world or my understanding of the way the world works. So here's just an example. I know I'm going to be free associating all over the place. Please. You're going to get into that, but it's like what are the coolest studies that we ever did? And I totally credit my postdoc, Matthias Gruber, for this. He came into my lab. He was originally German, came in from University College London.

And he told me he wanted to study curiosity and its effect on memory. I'm like, this is just – I am being totally closed-minded. I said, this is just a dumb topic. You know, it's – everybody knows if you're curious about something, you'll remember it better. It's just because you're interested, right? So he said, no, no, no. This is really interesting.

And so he did this experiment and I got on board with it. I, you know, we really kind of collectively, it was just this beautiful thing where I was exposed to something new and I got excited about it. And so the idea was we would give people these trivia questions. And so it's kind of like a pub quiz, right? You sit in a pub quiz. Sometimes you get a question and it's like, I don't know the answer. Sometimes you get it and you know, I know and it's like, I don't know the answer.

Sometimes you get it, you know, I know it. Sometimes you go, I don't know. But God, I really need to know the answer to this. And you get this itch, right? Or sometimes your listeners, I mean, they're probably very curious people. That's why they listen to this. And maybe some of them go to your show notes afterwards because they want to learn more, right?

So we actually scan people's brains using functional MRI. And so we scan them when they get questions. And sometimes they had said, I'm really curious to find out the answer to these questions. Sometimes they weren't curious. And then we make them wait about eight seconds, or 10 seconds, I think it was, something like that. And then we show them the answer.

So they're kind of in suspense, kind of like you're watching Breaking Bad or something back in the day. People at commercials, and so you're like, oh, now I gotta find out what's gonna happen to Walt, right? So you're in suspense. You need to know the answer to this, or you don't care. Sometimes you just don't care. You're just sitting around.

So we show a little face, and we say, hey, how likely is it you think this person knows the answer to the question? Now, this is a totally dumb thing to do because they don't know this person. They're just looking at a face. They're just making some arbitrary decision. But I'll get to why we did that because that was, I think, the coolest part of the experiment.

But let's first get back to the trivia question. So we found that when we looked at brain activity, when we give people the question, right afterwards there is a burst of activity throughout the so-called reward circuit of the brain. There's a series, it's not really a reward circuit as we've discussed offline. It's really these areas of the brain that process the neurotransmitter dopamine. And unlike many other neuromodulators that go all over the place, dopamine is much more restricted in its effect. And so in the midbrain near the ventral tegmental area, sorry, I'm geeking out on this.

No, we've talked about that in this podcast. I think the key statement that you made that people should hold on to as we progress through this is that dopamine is not dumped everywhere. It's not sprinklered all over the brain. It's released in a fairly restricted sites in order to drive particular processes. That's right. I think that's sufficient for now. Yeah, yeah.

And so when we look at functional MRI, we can't measure dopamine, but what we see is activity in the dopaminergic midbrain area, meaning the area of the brain around the midbrain. And you see it in the nucleus accumbens or what's called the ventral striatum, which is another area that's super high dopamine reward processing area. The more curious people are, like on a one to six scale, the more activity you see. It's just like this beautiful relationship, right?

And it's not driven by the answer. Now there's a reason we probably didn't get it for the answer, but it's driven by the question. So it's not like they're like, oh, I learned something new. It's like, I want to get this knowledge. And so that's part one of the story. Part two of the story is we show that face right after the question. And if people are curious to find the answer to the question, they get a bump in memory for the faces relative to if they're not curious.

Now the faces have nothing to do with the trivia question, but it's being in that curious state that drives this dopaminergic activity in the membrane. So there's a whole lot of other studies, findings from that study. But basically, I think, god, I gotta, you know how sometimes you do a lot of studies, I mean, I published like 180 studies, so it's like, I'm trying to remember the exact, I think it was like functional connectivity between the hippocampus and the red brain

during the face was predicting better memory for these faces in general, something like that. We can put a link to the paper, of course, in the show note capture. So let me make sure I understand that when people are prompted with a question, that drives the release of dopamine. The amount of dopamine is proportional

to how curious they are to get the answer to that particular question. And then the dopamine itself, if elevated, because they are very curious, can increase the probability that they will remember the answer. It creates a milieu, an environment for better memory, but that can confuse us and make us think

that dopamine improves our memory, but it's that curiosity increases dopamine, which increases the capacity to store information that comes subsequent to curiosity. Beautiful synopsis, but I'll do two cheerful amendments. So one is, um, technically we're not measuring dopamine. So I have to be very clear about that. This is bold signal, meaning it's, you know, metabolic activity, but it's following all the usual suspects of where you'd expect it to be. The second thing is I

do think that dopamine is playing a part and I mean it definitely facilitates plasticity. So I do think it helps in learning the answer for sure. And there's a whole theory called synaptic tagging which basically says that if you just release a bunch of dopamine and then you have these which basically says that if you just release a bunch of dopamine and then you have these potentiated synapses that you can dry plasticity in those synapses, even if it's not happening at the same time. But what's really cool is the face has nothing to do with the trivia question. The theory that we have is when you get that bump in dopamine activity, you're motivated, you're energized to get the answer, and you're driven towards a state of plasticity.

And now giving you something that has nothing to do with this question, and boom, you got it. So when people ask me, and they ask me a lot, how best to elevate their brain dopamine, one reasonable answer based on this study is curiosity, to engage curiosity. Do you know the quote by Dorothy Parker? The cure for boredom is curiosity.

There is no cure for curiosity. I believe it was Dorothy Parker. I love that. If it wasn't, I'm sure we'll find out quickly in the comments on YouTube. Older people show the effect just as much as younger people do. If it wasn't, I'm sure we'll find out quickly in the comments on YouTube. Older people show the effect just as much as younger people do. Kids show it just as much as older people do.

It's just something that sticks around. So speaking to your point, if you are surrounding yourself with things that will stimulate your curiosity and if you're open to that curiosity, we can talk about knowledge gaps and all these things that stimulate curiosity Novelty is another one Richard Morris has some beautiful data on this with rats But emma do so and I too have some data with humans Surprise all of these things. I have a little chapter in my book on this Drive that system. So the dopamine system dopamine system

So basically if you expose yourself to opportunities to be proven wrong, you expose yourself to new people, places, situations, and you allow yourself to be energized by these things and not be scared and anxious, not be like, oh this person's saying something that I disagree with, I can't deal with this, you know, or oh we figured this out 30 years ago, we don't need, nothing's new here. If you can be open to that, I can't deal with this, you know, or, oh, we figured this out 30 years ago. We don't need nothing's new here. If you can be open to that, I would argue that you're going to be engaging lots of plasticity and that's something that's preserved in old age.

Recently we had one of the world's experts on romantic relationships on this podcast, Esther Perel to be specific. And we talked about a lot of things related to romantic relationships, but she said that one of the most sustaining factors for romantic relationships over long periods of time is a sense of curiosity, both about the other person, but also about oneself and how one changes

in the context of the relationship, and also curiosity about where the relationship could eventually go, where one to continue to invest in it. So this word of curiosity seems to be a resounding theme. I'm struck by, although it makes total sense, that curiosity would drive dopamine release in these pathways, that novelty would drive dopamine release in these pathways, and that also in the physical realm,

dopamine is so important for physical movement. I don't think this is a coincidence, right? Somehow evolution organized this neuromodulator dopamine to be involved the way I think about it is in both a physical movement, it's required for it in fact, as well as cognitive movement. What we're really talking about is cognitive forward movement

if there is such a thing. Is there a, we're both neuroscientists, but you're the memory researcher. Is there sort of a word or a framework for thinking about cognitive movement forward? Meaning as opposed to just recycling past ideas and memories, the notion of taking memories and actually putting them, as you said earlier,

into the present to anticipate the future, actually forward mental movement. Huh, that's a really interesting question. Well, first of all, I want to be careful in not to say dopamine does this because it's a trap, right? Well, to be clear, you observed heightened activity in a dopaminergic circuit.

So the idea that it would not involve dopamine is a bit of a stretch, but you didn't directly show that it was dopamine. So you're being very exact. I wouldn't be exact and just say that assigning a single function to a chemical is risky. But that said, I do believe there's a link. One of the things that you see is in Parkinson's disease,

dopaminergic neurotransmitter mission is shot. And depression is also a symptom of Parkinson's disease. It's quite a severe one, in fact. And so what I think one theory goes is that dopamine energizes us to seek rewards or to seek information, right? So a big part of movement is you move to get something. It's approach, right?

They talk about approach and avoidance as basic kind of things that you want to program. And so, a person with Parkinson's disease has a problem with willful movement, tremors and stuff too. But I think that dopamine is involved in this kind of energizing you to move. I think it's involved in energizing you to seek information. I think it's involved in energizing you to seek rewards. And so I do think there's some kind of a common pathway there. And it speaks to this issue of the difference which you've talked about and I talk about a lot as wanting versus liking. And so Kent Barrage at Michigan's great work on those recent

gobs and gobs of manipulations of dopamine activity and what he finds is an animal Let's say that it's deprived of dopamine It will go for rewards just fine. It just won't work for them It won't do the work that you need to get a reward. But if you just put it in front of them, they'll take it. So what dopamine – it is heavily involved with these opioid systems that does drive reward responses and it's heavily involved in learning about rewards and that's why you get a big dopaminergic bump when an animal gets a reward because you're learning about

the reward and what predicted the reward. There's a little bit of a credit assignment process that takes place. What's interesting is you get this too with actually my colleague at Davis, Brian Wilchin, some beautiful work where he's looked at trace conditioning, which is when you have like a, let's say if you play a tone and you wait a long time, and then the animal gets a shock, right? And so what you find is that the animal learns to be afraid of the tone. But it's such a long time in his thing, I think it's on the order of 10 seconds or above,

the animal has to be somehow doing something to be able to blame that tone for getting shocked, right? And so what he found was that there's this burst of dopamine activity in the locus rullius, which is actually known for norepinephrine, but there's really cool work on dopamine in the LC now modulating hippocampus. Sorry to get all nerdy here, but... No, no. Trust me, this audience likes nerdy.

Okay. I think that's part of why they're listening. A locus rullius is just an area of the brain that tends to sprinkler large brain areas with epinephrine, nor epinephrine nor adrenaline for alertness. So somewhat distinct from the dopamine system, but you're telling us it can also release dopamine. Yes, that's right. And sometimes they co-release from the same neurons, from what I understand. And so what seems to be happening is, and he's studying this now, but what seems to

be happening is it's not that the animal's going, oh, I just heard a tone, I heard a tone and then they get shocked. It may be more like they get a shock and then they get an immediate what just happened and then they get a memory retrieval of the tone. And that allows them to put the two together to learn that this tone caused the shock, right? And dopamine seems to be playing a part in that learning process too. So it's not just about reward.

It's really kind of, you know, the next time you hear that tone, you might, if it were a real threat, you could actually escape from it, right? And there's this whole act of avoidance literature that you can look at with these approach circuits that are actually quite useful for avoiding threats and avoiding punishment.

So it's really, to me, I see this role for energizing. And that's often rewards. I like rewards as much as the next guy. Look at how much coffee I drank when I got here. So it's not that, but it's just that it's mobilizing you, I think. I'd like to take a quick break and acknowledge our sponsor, AG1.

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you can go to drinkag1.com slash Huberman to claim their special offer. Right now they're giving away five free travel packs plus a year supply of vitamin D3 K2. Again, that's drinkag1.com slash Huberman to claim that special offer. One thing that we talked about just briefly earlier was this non-sleep deep rest protocol

that in yoga tradition is called yoga nidra or yoga sleep because you lie down, it's self-directed relaxation, long exhale breathing to slow your heart rate, et cetera, et cetera. I called it not an NSDR, not to appropriate it, but because the language of yoga nidra is a little bit of a separator for people, it sounds a little bit esoteric, right?

And non-sleep deep rest tells you what it is, right? There's a study at the University of Copenhagen, I can provide a link to it in the show note captions, and I'd love your thoughts on it, that show that people who do this practice, this is a PET imaging study, so positron emission tomography for those that don't know, and they see significant increases in striatal dopamine

in the condition of people that do this self-directed relaxation, as opposed to a more traditional meditation. And this is why I say that NSDR is useful for restoring mental and physical vigor, which translates to this idea that dopamine prepares us for, or is a reservoir for potential movement, typically toward rewards.

And I love that we're talking about some of the other facets of dopamine because all too often people think about it as pleasure or motivation, and certainly it's involved in motivation. And I'm very happy to learn that it's also involved in learning. I think that's a novel perspective on dopamine,

and we hear so much about dopamine. Do you think that when dopamine is released as a consequence of curiosity in a way that primes the memory system that we become entrenched in particular behaviors or routes of pursuing curiosity to the exclusion of others? What I'm thinking about here is a kid. We've seen these data, kids with ADHD

actually have terrific ability to focus if it's something that they're really excited about, really curious about. So you give a kid with ADHD who loves video games a video game, and they're like a laser. So it's not that they lack the capacity to focus, it's that they have a harder time dropping into focus. But it seems that because of the learning

Dimension to dopamine that these circuits could potentially quote-unquote learn that it's video games that provides that feeling of focus to the exclusion of other things meaning how does one keep a diversification of Inputs to the dopamine system so that we're continually driving dopamine through lots of different things as opposed to just social media or just video games or just pick your favorite thing. Because becoming a functional human being involves the requirement to focus on many things,

not just the things we were curious about. Yeah, yeah, yeah. I mean, to me, I talk about this a little bit in the book, but to me, and if you look at the literature too, you can see this, a big part of being curious is the appraisal process, so to speak. And what I mean by that is saying something happens, right? Let's say something in your environment happens. If you're going to, you have a decision to make, is this interesting?

Is this important? Is this scary? And I think the thing is that you need to be open to that possibility that it's interesting. So let me just give you like an example that I often give. Let's say you're walking in a neighborhood. You're traveling like you do for many of your events and you walk into a new neighborhood you haven't been to. It's nighttime, kind of poorly lit and you hear a loud noise, right? You could be like, well, that's a gunshot.

I better hide or I better run or you could be like, oh, maybe there's a club nearby and there's like a cool band playing. I should go check this out. That appraisal is really critical for how you respond. And so it's not just a matter of curiosity happens. It's a process of cultivation and it's a process of appraisal. And so, I mean, this is I think, I'm not a wellness guru or anything, but it's like, I think this is one of the cool things about mindfulness training is it forces you to take the mundane and be curious about

it. And when you start paying attention to your breathing, my friend, Mishi Jha has really kind of turned me on to this. She wrote a book on mindfulness and meditation. And one of the things that happens is you're breathing and you realize, wait a minute, this one isn't the same as the last one, right? Or you can do these meditations. I'm sure you've done this, right? This part of like, the sound is different. I'll sit in the backyard doing, thanks to you, I do this morning 10 minute thing.

And so I'll be out in the backyard and I'll be like hearing some sound and I'll be like, oh, that sound, there's a bird there. I didn't even notice that, you know, and then there's some other sound. I'm hearing the freeway. That's annoying, but I heard it. So these – it's really a matter of paying attention in some ways and being open to it. And I think this speaks back to this thing about as you get older, sometimes people find it scary to be in a new place.

People find it scary to meet a person who's different from them or so forth. I mean, I love listening to music that's a little bit out of my comfort zone, so people hate it, you know? So I think some of it is sort of cultivating being comfortable with discomfort. I think it's such an important theme. I feel like nowadays, in part because of the algorithms on social media, we are fed things that feed our progressively greater and greater scrolling and dwell time, as it's called. The algorithms are measuring clearly how long we dwell

on a given image and what's in that image and et cetera. But it'd be nice to cultivate an algorithm for curiosity. Surely it can be done. I mean, you got all these smart computer scientists and AI folks. And we come into this world naturally curious. All primates, including humans, will visually fixate on anything that's novel, right?

And study it. And try and make predictions and gain understanding. Maybe now would be a good time for us to discuss a little bit about the circuitry involved in memory so that we have that as a template to digest some other themes in memory. Most people are probably familiar with the so-called hippocampus, which is, I mean,

seahorse. It looks a little bit like a seahorse, although the anatomists had a little bit of an imagination there in my opinion. But hippocampus, let's add to it prefrontal cortex, which you've already mentioned, and then these neuromodulatory systems. So if we were going to assign a one sentence definition, functional definition to each of those areas, what would you say the hippocampus does? If you need more than one sentence left. Well first of all, I'll add a whole lot of other neocortical areas we can talk about.

Please, and let's add those in, but I think if you can start with three, I think then folks can digest it. Yeah, so the hippocampus is controversial. I mean, it's the most studied area of the brain, arguably, except for maybe V1. Um, Visual cortex.

V1. Yeah. Uh, and, uh, but I believe in my colleagues do, I wrote a big paper with Howard, I can delete Howard, I can bomb and Andy on Lenis on this who, um, you know, from Davis and, uh, we believe that it's about linking various experiences to a context. And what I mean by that is you've got information about smell, high level vision, high level semantic knowledge information, right?

And the hippocampus' wiring is really set up to not understand what's going on. So the late David Morrow's pioneer in computational neuroscience proposed that what the hippocampus is about is what's he called simple memory. It's basically saying, I know Andy Huberman. Sorry. He's okay. He used to call me Andy. That's fine. Yeah. Long story.

That's a Davis thing. You would understand. So, um, uh, so I know Andy Huberman, right? But to have a memory of this moment that's separate from, let's say I saw you at some neuroscience retreat when we were in, when you were in grad school, I have to have some part of the brain that doesn't know who you are to some extent, right? Because I got to keep them separate. And so there are the hippocampus, what it'll do is it'll form a memory that's not an Andy Huberman memory It's an Andy in this place at this time in this context

And that's what allows it to support what's called episodic memory, which is your ability to say I Went to Washington DC once and I remember going to the Smithsonian as Opposed to your knowledge about what generally happens in Washington, DC, or the presidents there. Oh, that's where a lot of politics happen. Oh, the Smithsonian is a place in DC. It's a memory of your being there at a particular place and time.

Now, there's other parts of the brain that allow you to associate that information in a meaningful way and to be able to actually expand on that context and create these narratives and these stories about it. Where the prefrontal cortex comes in, and it's a huge area. It's about one-third of the primate brain. So it's just massive. There are a lot of people who go, well, there's no real,

there's a bunch of different areas and I'll do different things. And I subscribe to the view that that is very true. And at the same time, there's a global function of the prefrontal cortex, which is what's called cognitive control. It's this ability to say, I'm going to regulate my movements, and I'm going to regulate my perceptions and my thoughts based on what's important to me in terms of this higher order goal, right? So when I've tested, for instance, patients with prefrontal lesions, I'm sure Mark Desposito talked to you about this.

It's like the hallmark of them, they used to say, well, the prefrontal cortex, it's important for working memory. and you could record from neurons in the prefrontal cortex or look at fMRI signal and if a person or an animal is holding something in their mind like a phone number, neurons or bold signal and MRI will be highly elevated. Their activity will be elevated throughout this period of time where they're holding in mind. But it turns out if you just ask somebody with a major prefrontal lesion, here's a bunch of numbers, five, two, seven, eight, you know, I ask you to tell them back to me

in right order. They can do it just fine. But now I start to distract them, I move my hands around, there's a plane going on, you know, flying outside the window. I mean, I had that literally happen once. Now they start to bomb it because their attention is not controlled by their goal. It's controlled by the environment around them. And so this is where things get really interesting. So I once tested a patient and I'd heard about this, but until you see it, it like doesn't register.

It really blew my mind. So there's a test called the Wisconsin card sorting test and we don't have to get into all the details of it. But basically it's this test where people learn some rule about where to put a card on a table, right? And they don't get told the rule. They just learn it. And patients learn this with prefrontal damage, learn it just fine, right? And they don't get told the rule, they just learn it. And patients learn this with prefrontal damage,

learn it just fine. Is it that they get a error signal or a correct signal if they're doing it in the right direction over time, they just kind of, the brain figures it out. Yeah, yeah, so maybe I'll give a little bit more background, but I don't want to go in the weeds. No, that's okay. I mean, if I'm correct, if I'm wrong,

I forget the Wisconsin Card Soaring Test details, but you know, like they're told to just start showing the cards and that the correct algorithm will reveal itself by a series of error and correct signals. And so maybe I'm taking all the red cards and putting in one pile of black cards and putting them in another, I'm getting error signals,

so then maybe I go odds, evens. Maybe I divide by suit, if it's depending on what kind of cards they are. Maybe I organize by even odd alteration. And sooner or later, the brain figures it out. Yeah, exactly, exactly. And you don't need a prefrontal cortex to do that, which is surprising, but you don't, you can do it.

And- So there's context dependent action and learning without the prefrontal cortex. Yes, but let's unpack this context then, right? So now you've been, let's say, putting all the diamonds in one pile. You've been putting all the spades in another pile. So now I changed the rule, but I don't tell you and you put the queen of diamonds in the diamond pile, let's say. And now I say, nope, that's wrong. So now you have to say, wait a minute, that was right all this time, what's going on? This is like life.

This is like life, right? The thing that used to work for you no longer works. So you keep doing this, and a person with an intact brain will eventually figure out, OK, that's not working. I'll try another strategy, and then they'll learn the new rule, right? It's not easy, it's pain, but people will do it. This patient in particular kept on using the old rule.

And so you have to give a series of hints going like, what's your strategy here? And they're like, they'll tell you I'm putting it according to the color. And then you, okay, well, does that appear to be working for you? And they'll go, no. They'll just keep doing it. They perseverate. They perseverate. But the interesting thing is he knows it's not working, but he can't help himself from

doing it. And so what the prefrontal cortex is, it's not about this declarative knowledge about what you should do. And I think this is very deep because I think often we get more realistic about people's actions, especially for people who have head injuries or something like that. And it's like you can have all of these beliefs that you want to have, but you need the prefrontal cortex to translate these high order beliefs, things that are very abstract, into actual concrete action.

Otherwise, what you do is not going to be dictated by that knowledge. So how this relates to memory is we're constantly barraged by information. I think it might have said something like 35 terabytes. I don't know. But it's a big number and the estimates get bigger and bigger every year. So we're barraged by information. There's no way you can even pay attention to it all, right? So you really rely on the prefrontal cortex to be able to say, this is what I'm doing right now. And everything else, it's noise. Here's the signal that I need to focus on. And that's super important for memory,

because one of the things you see in old age is older people are bad at most memory tests. But it turns out in labs we kind of overestimate that. And the reason we overestimate it is we're giving them a test, which is something hard. It requires a lot of focus and it's not something they do every day. But Karen Campbell and Lynn Hasher, these great cognitive psychologists, did this cool experiment where they had a bunch of other stuff that people were supposed to ignore

in this memory task, where they're studying a bunch of things, they're trying to memorize a bunch of stuff, but there's stuff going on they're supposed to ignore. The older people were just as good as the younger people at remembering the stuff they were supposed to ignore. They were just bad at the stuff that they were supposed to pay attention to.

That's so interesting. Maybe you could say that another time. You said it very clearly, I got it, but say it one more time, because if anyone missed it, this is super important. Older people can. They were bad at remembering the stuff that they were supposed to remember,

but they were just as good as the younger people, maybe even better, but definitely as good as the younger people at remembering the things that they weren't supposed to pay attention to gosh it speaks to almost two Parallel processing streams for memory if I'm not mistaken Or maybe so what's going on there? Is it that one form of memory involves the suppression of? Information and that circuit is actually quite active

in these older people and young people. Whereas curiosity for, and the ability to remember and integrate new information is somehow diminished in older people. Earlier we were talking about how that's not the case. That curiosity, if curiosity is intact, memory is intact and growing. Yeah, well, okay, I should say the benefit of curiosity on memory is intact in older people. I got that wrong

I don't know Mattias could tell me if I just Email him if at a break or something, but I don't know if curiosity itself is as high in older adults I would self-reported or? I would guess no, but this is why I asked about movement earlier. Curiosity is also linked to your ability to access novel scenarios. Of course, online you can just thumb scroll or click and access all sorts of novelty.

Is there any, there must be data as to whether or not people in their 70s, 80s and 90s are scrolling social media to the same extent that younger people are. I don't know, but I can say two things to this. One is that definitely there's a lot of work on media multitasking. The short answer is bad for memory.

Okay, so scrolling is bad for memory. Well, media multitasking is bad for memory. Okay. So scrolling is bad for memory. Well, media multitasking is bad for memory. The tech thing is a super fascinating area in general. It's really how we interact with the tech that's bad. But if you're an older adult, your frontal function is not going to be as good. You will be more distractible. You will be more likely to go off course. And so that scrolling is going to be more potent,

because as you pointed out, the algorithms are all designed to suck up our attention. So psychologist Herb Simon came up with this beautiful term called the attention economy, right? And so the idea is that the more information that you have in front of you, the more impoverished you are in terms of your attention. So there's no such thing as free speech, because it's like you have a limited supply of attention.

So everything has a cost. So the more information you have in front of you, the harder it is to pay attention to what's important. And that's where I think the older adults really lose some of their functioning because basically I talk about in the book, and it's not a perfect analogy, is neurons are functioning kind of like a democracy in the sense that real democracies involve these political coalitions or alliances, right?

I mean, people talk about the right and the left, but that's dumb because it's like there's really just alliances between people who like different things, and they just form these convenient alliances with each other. But let's just imagine neurons kind of do this in the brain, right? And so you have, in theory, to be able to pay attention to something, some coalition of neurons has to be firing a lot that is corresponding to the thing that you're trying to pay attention to. But if something is salient, bright, shiny, loud, it's just grabbing your attention.

What's going to happen is, is that those neurons start to shout down the neurons that are trying to keep you on what's not shiny, but it's important. Right? And so what happens is with the prefrontal cortex, you can bias that competition. Now that's the term that people cortex, you can bias that competition. That's the term that people have used in literature. That allows you, so what people have found for us is just a really cool finding again

is you can find in the visual cortex neurons that fire when you're seeing something red, neurons that fire when you see something blue, let's say, right? I'm kind of distorting the picture, but you get the idea. So if an animal is trying to hold in mind something, I'd say hold on a mental picture of something that's blue, what happens is the blue neurons are firing in the visual cortex even though the animal is not seeing blue, right?

It's just they're thinking about blue. You damage the prefrontal cortex, nothing. So you lose that selectivity. So what's happening is the prefrontal cortex is biasing the competition and saying, I know blue's not shining in front of you. There's no shiny blue thing in front of you right now, but I need these neurons to stay active. And so it's doing this modulation to help out the neurons that are keeping the information that's goal relevant. So what happens when that communication goes, let's say due to hypertension, diabetes,

you get all this white matter damage that happens with old age. And this is really a big thing that is very preventable with the right protocols, so to speak. I'll just bring it, white matter are the fiber tracks, the wires that essentially that connect neurons across long and short distances.

Exactly. Yeah. And so if you damage those long range tracks, the prefrontal cortex is not efficiently able to bias that competition. And so now the inane gets remembered at the expense of the important. That's I think the key thing and a lot of that's why people talk about the prefrontal cortex as the central executive. As anybody who's worked a job knows, it's like the executives are useless, right? He's trying to get an executive to do, I mean,

except for some who are useful, but then they don't really run companies very well. There's some CEOs that are doing spectacular things, but- Yeah. Well, okay. we won't go there. Controversial, shall we say. But anyway, so a good executive, their job isn't to micromanage. Their job is to say, here's the big picture, here's my vision for the company, and I want everyone to be working towards this goal, not sifting through the mailroom, not paying the bills.

And so what happens is that when you have certain kinds of things that happen with aging, like damage to the white matter, that happens through essentially tiny cerebrovascular events, most likely. And we've done some research on this in our lab in collaboration with Bill Jagus, who's now in Berkeley, and Charlie DeCarli. You can measure this in MRIs with a measure called white matter hyperintensities. You use a scan that shows up little bright spots where the white matter is probably damaged. What you find is that these people with white matter hyperintensities actually have memory

performance that's as poor as people who have hippocampal atrophy probably in the early stages of Alzheimer's. And they're also bad at controlling information even when they don't have to remember something. So it's like a double whammy and it's kind of like the executive is trapped in a remote place and they got no internet access and no phone and so they can't communicate with the company. It's just doing their own thing, right? That's a little bit of what can happen with aging.

It doesn't have to but that can happen. You see this to a really great extent in many disorders. This is why so many disorders really affect control and frontal function, multiple sclerosis, diabetes, many kinds of things. We talked about brain fog and many kinds of inflammatory conditions will affect it. Depression, clinical depressions. I've seen people, older adults with depression, who are cognitively more impaired than people in the MCI stage of Alzheimer's.

Really? Yes. So depression is dangerous for memory. It's terrible for memory, and it seems to be a risk factor for Alzheimer's as well. Do you think that depression is dangerous for memory and a risk factor for Alzheimer's because it is, by definition, anti-curiosity?

I would probably not say that. I would say also I don't know what... I mean, once you kind of get into these things in the epidemiological world, everything interacts with each other, and there's genetics, and there's environment, and blah, blah, blah. Depression means poor sleep, which means poor learning, which means that's all... I think that's a big part of it. I think that's a big part. But you do...

Okay, so let's go back to your question question because I do think curiosity is affected by depression. I don't know the research on this but I would be shocked if it isn't. And I do think that dopamine activity is disrupted in depression and your motivation to get anhedonia is the – one of the hallmark symptoms of depression as is rumination, by the way, which is memory retrieval of preferential negative retrieval of negative events and cogitating over them. I'd like to take a quick break

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to get early access to Function. You probably think a fair amount about age-related cognitive decline and Alzheimer's. And I'm just curious at a personal level, what are the sorts of things that you do to try and offset cognitive decline? You seem to be a very vivacious and curious person. I've known you a long time,

and I don't know whether or not you were caffeinated every time we met, but you have a lot of energy. You're a very curious person. You just wrote a book, we'll talk more about, and you're going on podcasts, you're doing a lot of things besides running a world-class research laboratory. So clearly a lot of curiosity. What did the data say about ways to maintain

or enhance one's memory capacity? With the understanding that curiosity is probably involved as we talked about earlier, but at a really basic level. I mean, a number of things leap to mind, but I'm just curious what your, if you had to pick like three to five things that are clearly substantiated in the data as supporting the maintenance or enhancement of memory

as we get older, what are those? I mean, as a memory researcher, I almost find myself like ashamed when I talk about these things, because as you know, so many of the most important factors are ones that are related to just health. So for instance, you mentioned sleep, that's a big one.

Actually, there's a beautiful study that speaks to this that was done, 29,000 subjects in China and they followed them up for 10 years. Now at the beginning of, so they divided people into three groups. They said, okay, here's, well, what they said is there's six lifestyle factors that we're going to investigate. One was I think engagement in cognitive activities, I think one with social engagement, one was physical exercise, not smoking, I think no alcohol, but they identify these lifestyle factors that were basically just kind of

good lifestyle factors. So they get people who have four to six of these lifestyle factors going versus zero to one of these lifestyle factors. I'll just take the extreme. When they start, they're all the same. Ten years later, the people with four to six lifestyle factors going for them are performing almost twice as high on memory tests as the people with zero to one lifestyle. Wow.

So these are people exercising, paying attention to their sleep, social engagement. What are some of the other, I'm guessing low inflammatory diet. Yeah, yeah, definitely not smoking. And smoking and alcohol, I think were big ones. The smoking one is interesting because we know smoking can cause cancer and cardiovascular risk is real there.

Although there are some data, as I understand, that nicotine itself, not smoking, vaping, dipping, or snuffing, but that nicotine can be pro-cognition and maybe even pro-memory. And nowadays, people are using nicotine more and more. I'm not a big proponent of this because of the blood pressure increase and the typical routes of administration are dangerous, But nicotine, I've been told is protective

for Parkinson's and Alzheimer's. Is that true? Well, let me, by the way, I just have to say I forgot healthy diet, healthy diet was a big one too. Which I define as people wonder what is that? And there are all these online debates about vegan, vegetarian, carnivore, blah, blah, but but but I think most people in the world Are omnivores most and I think it's very clear that the number one thing for healthy diet is to try and get most of one's food from Non-processed or minimally processed sources. Yeah, we're set you in the right direction. Yeah. Yeah

So I was actually emailing with Dean and I issue sure Zai who really talked a lot about this Yeah, they do great work So I was actually emailing with Dean and Aisha Shirzai, who really talk a lot about this. Yeah, they do great work. They do great work. And so they were actually sending me some stuff and I had known about some of this, but like Mediterranean diet has worked really well. Olive oil, fruits, vegetables, fish, eggs,

limited amounts of meat. Although I happen to, I'm half Argentine, so I'm a. Yeah, you like your steaks. I do. Yeah. Which I think, you know, is, let me come back to this point because I think it's super important, but leafy greens were a big one.

They pointed out a Rush Presbyterian study that I didn't know about that put people on, I think it was called the DASH diet, and it included leafy greens as a big part of it, and that had a dramatic increase in cognitive, I mean, dramatically preserved cognitive performance in people who are on that diet. So the healthy diet is a big part. Now nicotine is interesting. So if you notice a lot of people with schizophrenia smoke, and one of the things that's been found is that nicotine does seem to improve functioning in people, cognitive functioning

in people with schizophrenia. Now I think the big thing to remember about any kind of drug, and this goes for food effects probably too, but especially drugs, is there's huge individual differences, huge. And so, I mean, just to give you an example, I could not function without that coffee that I had this morning and then coming in here. But my daughter wouldn't not be functional after those cups of coffee. Some people really are affected by these different things differently. And then of course, there's always a dose response curve and they often follow these inverted U's.

So Mark Desposito, who was my postdoc mentor, did a lot of work with dopaminergic drugs. And a lot of people had done these drug studies early on on cognition. They would find no effects or sometimes it would make people worse. And what he found was that if you looked more carefully, there was an inverted U effect where some people, and it depended on their working memory capacity, were actually benefiting from the drug. And then these other people who were, let's say, I can't remember, higher or lower, were

doing worse. And there's a genetic component to that, unsurprisingly. Dopamine transporters play a role and so forth. And so now you start to get into all of these gene environment drug interactions that are just – I would really caution people against saying nicotine is good, nicotine is bad. I think it really, really is a much more complex issue. It's just like marijuana, right?

So you can look at smoking weed in adolescence. For people who are at high genetic risk for psychosis, it dramatically increases your risk for psychosis. That's my understanding. Yeah. Although the times I've said that on the internet, I caught a lot of pushback from some of the cannabis researchers, but then having invited

one of them on this podcast, I then got subsequent input from other researchers, which counter their narrative, which we can both say because we're both research scientists, that's what you call a field. Yeah. Sorry, maybe cut out any misinformation I might have said in the end. No, no, no, you didn't. You didn't.

I think the point is just that it's very clear that there are certain individuals for whom high THC consumption can trigger psychotic episodes. Yeah, and we're seeing this with- But not everyone. Yeah. I mean, we're now interestingly seeing this with psychedelics where it's like all these positive effects of psychedelics We're being are being brought up But you know a lot of people remember the negative effects on people like rocky Erickson from the 13th floor elevators or like

Sid Barrett from Pink Floyd who became psychotic after doing large amounts of LSD. What was the first example? Rocky Erickson from the 13th floor elevators, great psychedelic band. Oh, psychedelic, okay, we'll talk more about, Charne is himself a rock and roll musician and loves rock and roll, hence the reference to Rick Rubin earlier. And there's a photo of Rick here in the studio

that our photographer, Mike Blayback, took. So we were looking at that together. So yes, psychedelics have claimed the minds of certain people, made them, helped contribute to their preexisting, presumably psychosis. I should also say in fairness to the other compounds out there, methamphetamines have also significantly contributed

to the progression of psychosis in many people. So it's not just psychedelics. Yeah, yeah, yeah. Right. Yeah. And then of course, there are those who have somehow managed to take psychedelics and become more sane. Yeah, I saw some- Or at least remain as sane as they were before.

Yeah, and of course sanity's in the eye of the beholder too, but what I'll say is that yeah, and you can see this, actually there's some new concern about Adderall and stimulants, and if you're giving it to people who might be at high risk for schizophrenia, it might also promote psychosis. That makes sense, given the noradrenergic dopaminergic

involvement in schizophrenia and those drugs are pro-noradrenergic dopaminergic in general. Yeah, yeah, exactly, exactly. So it's really a much more complicated interaction and I think this is where this whole realm of personalized medicine will be super helpful But there does seem to be a broad general effect for certain dietary Interventions berries seem to be good leafy greens seem to be healthy. We talked about the exercise

Yeah, and my understanding I've been looking at this in detail lately, but I'd love your thoughts is that while everybody We now believe men women women, et cetera, should do both cardiovascular exercise, so to speak, elevate heart rate for 12 to 60 minutes kind of thing, depending on the intensity, as well as resistance training to maintain neuromuscular function, offset sarcopenia, et cetera. To me, the really impressive effects of exercise

on learning capacity and the brain in terms of brain health seem to come from cardiovascular exercise. And that could just be because that's what's been emphasized in the studies. But even when one looks at something and compares the best human studies, it really does seem like getting blood flow up to the brain, getting a nice release of neuromodulators

into the brain facilitates learning. And then of course people have to do something with that learning, right? So do you make an effort to exercise for the specific purpose of maintaining or enhancing brain function? Yes, yeah, actually. So I like, when I finished my book,

I limped to the finish line. I had all sorts of crazy stuff happen. I won't depress the readers with all the crazy stuff that happened. I'm sure people would be curious, what does it take to finish a book and how much, do you mean you took a toll on your body? It took probably, I mean, I don't know, I probably lost some biological years in that, but it was really like, I mean, it was great. I mean, it was really an emotional roller coaster though, but then I had a bunch of...

I'm trying to do science, write this book basically in my spare time, which doesn't really exist as you know how it goes. And then I had life happen. My mom was in the hospital, my cat died on my birthday. It was just like... Yeah, see, I didn't want to impress people with all this stuff. It's real life. I'm just sorry to hear it.

Yeah, no, no, no. It's real life. I'm just sorry to hear it. Yeah. No, no, no. It's okay. So then I finished my book and I was just thoroughly thrashed and I had a sabbatical because I wanted to have time to promote the book and educate people about what's in the book, which I'd never gotten a chance to do before. It's like doing this. Fantastic.

I get to talk to people. So I really wanted to make some changes. And actually, this gets something we were talking about before we started recording, which is after I wrote the book, it's all, you know, it's going in the proofing stage. I was talking to my daughter and just, you know, out of the blue, she said, we're talking about ADHD. And she's like, Dad, you totally have ADHD. And I'm like, what? And I'm like, oh, Gen Z, overdiagnosis of ADHD, whatever, right?

And then I remembered when I was a kid, my school contacted my parents and said, you have ADHD. He has ADHD. And it was interesting because it was like, I actually was ahead in school by a year and I got held back because I just was so socially bad. I couldn't stop talking in class and I was just like really awkward and

impulsive and, um, um, and so, but the, you know, it was the seventies, nobody did anything, you know, and, and I had all sorts of behavior issues and so forth. And there are other factors going on too. But it really got me thinking, oh my God, I gotta make some changes. I'm living this unsustainable life where I'm jumping from crisis to crisis to crisis. And I say, I don't have time for blah blah blah.

And so, my, again, this is gonna sound depressing, but it's got a happier ending. So my dog had died in 2019 of cancer and that was my first dog. So I thought I'm never getting a dog again. And in 2020, in the pandemic, I got another dog. Good for you. Yeah. What kind of dog?

She's a, both of these were shelter dogs. Great. Good for you. They're all mixes. I'm sure there's some pit bull in her, because every shelter dog either has pit bull or chihuahua. Exactly. But she looks very Belgian Malinois and she moves like a Belgian Malinois. Beautiful dogs. Yeah. And they're so smart and super athletic. I mean, she can jump vertically. So when I'll

come home, she'll jump up and then push herself off me, which is like a very classic thing. And so that's why they can jump. Like she can climb up like seven feet up a tree to chase a squirrel. Yeah. They use these for military operations in tier one military. Yeah. Yeah. Yeah. They're trained to jump out of planes. Yeah. Parachutes. Yeah. Yeah. And she's, but she's a smaller dog. So our big, our older dog looked like kind of, she wasn't, she was actually a Kelpie mix I think, but she looked like a Rottweiler. And so everyone was scared of her even though she's the sweetest dog. This one, she's like smaller even though she looks kind of shepherd like.

Everyone's like, oh, your dog is so sweet. She's so cute. You know. You're like, but this one's the ninja. Exactly. Yeah. Yeah. I mean, all sheltered dogs have a little bit of a crazy switch in them, don't they?

It's like, it's tough for them. They're like feral people, feral dogs. Yeah. But they have big hearts. Yeah, yeah. Because they're eternally grateful. You give them a home. Yeah, yeah, exactly. And you know, one of the things that I was thinking is I missed walking the dog. I missed that activity. And so I make sure to do that every morning.

And this goes back to some of the activity things that we're talking about. I know I'm totally drifting away from ADHD, which is ironic. No, I see where you're going with this. Yeah. But this is a little bit different, but it's related, which is having a sense of purpose is very important for healthy brain aging. There's a Trends of Cognitive Science article I'll send you. It's one of these things that neuroscientists don't talk about because it's not – we don't understand it.

But it's hugely important as part of this whole phenomenon, what they call cognitive reserve. And having this dog that I'm taking care of, especially because my kid had gone to college, he's grown up living independently, walking this dog every day. It gives me, obviously I'm married and I love my family and I've got lots of them. I've got a lot of my students and so forth, but it gave me more and I'm exercising in a way that's kind of fun. I'm listening to podcasts and I'm moving.

And so that's something right there. It's not just the exercise, but it's the whole thing, right? I'm not doing something that I hate. So then I'm like, I hate running. I hate, I have this inertia because I've my ADHD brain doesn't like to do stuff unless it's shiny and fun, right? And I could go into work, I could write this book cause it's fun for me, you know? But so I'm like, how could I do this? And so I ended up shelling out for a personal trainer.

I blew my advance on a personal trainer who's great. And I go to see her and she tells me what to do. So I don't have to think about it. And it's fun. You're in great shape. Oh, thank you. You're a few years older than I am. And I haven't seen you in a while.

And I always have this slight fear when I run into a colleague again after a while. Because there was this joke that we didn't tell professors until we became professors about the so-called tenured look. I run into a colleague again after a while because there was this joke that we didn't tell professors until we became professors about the so-called tenured look. You see someone come in as a postdoc, you see them as a junior professor, and then you see them after tenure.

And tenure is a big milestone, right? It corresponds to academic freedom, et cetera. So it's a wonderful milestone. It's a wonderful thing that we both have this. But you see some people who got tenure and just go, oh goodness, they look like they're, you know, aged 25 years in five years. Yeah.

We also see this with former presidents, not all of them, but a lot of them. And so to run into you, well, I saw you on Lex Friedman's podcast, but then to see you on my charn's taking great care of himself, it makes me happy. It's not a judgment. It makes me happy because I love my colleagues

and I want to see them live a very long time because I don't subscribe to the idea that science progresses one funeral time of my favorite scientists. Okay, let's not attach that saying to me. It was a joke. No, I'm saying that there's certain scientists. I love my fellow scientists.

I do too. If you're out there anywhere, don't hate me. There are certain scientists that you'd love to see live forever and you're one of them. So you said walk in the dog, which presumably gets you some sunlight, a lot of sunlight in Davis, even in the winter. Cloud cover is bright up there,

it gets you on a regular sleep rhythm. So, but you said this sense of purpose, right? So, and I'm curious about how you now frame exercise. You said you don't like working out, you made an investment in your health by paying a trainer. So now you train regularly. And that's also an investment in your brain health. And if we were to go back to this notion

of sense of purpose, are you talking about a larger sense of purpose? Like, okay, I want to contribute to understanding of how the brain works. You're a brain explorer after all. And therefore the exercise and the money you put towards the trainer is linked to the ability to do that. Are you linking these nodes or are these kind of separate entities? Like I want to be healthier and here's a way to be healthier and ergo, I'll be around

longer to study the brain. To me, and again, you know, I'm not a social psychologist of this a little bit off out of my wheelhouse but to me the sense of purpose is kind of this existential thing of like You know, I got to take care of this dog and I got a you know And I am when I look at this dog and she's moping around in the corner. I feel bad But I feel like it's my responsibility to do something with my students. Yeah, with my students, I have... I was very, very fortunate to have many people leave my lab after the pandemic, which destroyed so many careers, and many people left my lab and I got faculty positions. I'm so

happy for them. But it also... It speaks to your mentoring as well. Oh, thank you. You do well because you have good people in the lab, as you know. That's true. But what was interesting was I'd finished the book, and my lab was relatively empty. And I did feel purposeless.

I felt that absence of that sense of this bigger thing. And so part of the work is, and this was like a thing that I felt doing the book promotion is, I feel a sense of purpose in explaining science to people. I got an email this morning as I was getting on the plane from somebody who was asking me a question about memory. And I was just like, this is so cool. You know, after you spend years lecturing students and some of them are sleeping in class and you wonder, is anybody really impacted by this?

And it's just been a beautiful thing. So that gives me a sense of purpose. class and you wonder is anybody really impacted by this? And it's just been a beautiful thing. So that gives me a sense of purpose. I've come up with, I've really rededicated myself to research and we're doing these huge computational models of learning and I'm trying to get, we're doing VR stuff and we're going to be doing all sorts of new things in the research. And that gives me a sense of purpose. But a lot of it to me about the connection thing that you bring up, it's super important because often I find myself again because of the ADHD thing.

For all of these things that I like, there's things that you have to do that suck. And for me, that suckiness is utterly painful. I mean – and I know there's a lot of people like – I know ADHD is over-diagnosed right now for reasons that are interesting And I know a lot of people it's very kind of fashionable to say stuff something like that Maybe I don't know people can be judgy about the stuff, but for me it really is painful I mean, I've actually found that it's hard for me to work with certain people if they talk slowly So I've really had to think about,

so I actually hooked up with an ADHD coach who has been phenomenal for me. And I know coaches are another controversial thing. I don't know that I'm not in my world. You wanna learn something, you learn something from somebody who's skilled in how to improve somebody at something. Yeah, yeah, well, you know, I mean,

I didn't know what to expect because it's like an unregulated world so to speak or minimally regulated. But the person I found was just amazing. And the first thing she had me do was she put down, had me write down a sheet of all my values and order them and rank them and stuff. I'm thinking this is such a waste of time. Sorry, Laurie, but I was thinking initially this is such a waste of time. Why am I doing this? I don't really value any. I don't know. I'm sorry, Laurie, but I was thinking initially this is such a waste of time. Why am I doing this?

I don't really value it. I don't know. I just do things. I don't necessarily value them or whatever. But then I started writing them down and then later I was talking to her about like this, some of my troubles with motivation and getting things done that I don't want to do and kind of infamous for having trouble getting things done that I don't want to do in terms of like administrative tasks and so forth. You're a real scientist.

Well, that's true, I guess. ADHD is- Any scientist that likes administrative stuff, I think I'm willing to call out as, what are they doing in science? Cause that's like, you're supposed to be focusing on experiments. So bravo.

So values then motivation. Yeah, so basically it's like, so then I put the two together and I said, I'm not giving myself credit for why I'm doing this. So this goes back to the whole, I mean, in a way it goes back to the prefrontal cortex conversation is what's my goal? If I'm going to see someone and have a meeting and I don't feel like going to the meeting because I'm tired and I'm bored or I want to just look at this YouTube video or I want to go on social media or whatever dumb thing that I would waste my time on, right? I say to myself, well, why am I doing this?

And I remind myself of that motivation and it kicks everything in gear because now I have that goal in place because the goal just doesn't pop up for me automatically. And so relating what I do to values is a game changer for me. But it's a conscious thing that I have to work on to remind myself of those values and connect them. And that's part of what I think people lose when they retire, for instance. I see this in people I'm close to who have retired, they feel like work is their only purpose. And so afterwards, they feel purposeless. And then they're just doing things like, you know, doom scrolling, or, you know, being

radicalized on, on the internet, or like, you know, going into like, but it's just like, whatever captures their attention. And I think so a big part of that sense of purpose for me has really been to get in touch with what do I really want? And I mean, this goes back to another thing with memory. And I know this is a total ADHD pre-association thing, but it's like, people often ask me, okay, fine, give me all this stuff for brain aging. And we didn't even get into hearing aids

and vision testing and oral hygiene and so forth. We'll talk about those three things. But what I tell people is, I can tell you lots of strategies for remembering names, for remembering where you've been for trying to remember like to do something in the future. Some of the hardest memory challenges we have, but unless you do them, do those strategies, I can't help you. And the problem is, is that, and this speaks to, I really liked what you said. We do have to talk about some exceptions like retrieval induced forgetting and some interesting things like the pre-testing effect, but your thing on study skills, I listened to a podcast and I was like the pre-testing effect. But your thing on study skills, I listened to that podcast

and I was like, the beautiful thing that you did with that, one of them, was that you said, assume that you will forget. Because if you go back to the earliest research on memory by Ebbinghaus, he tested himself and he actually created these weird words called trigrams that weren't really words. He tried to memorize them and what he found was within 20 minutes, he had forgotten about half of what he memorized within.

And I don't mean just forgotten, like he couldn't bring it to mind. It took him as long to re memorize them as it was if he had never done it. Right. So sometimes we have partial memory where we can't recall it, but we get some savings and it's easier for us to learn. He didn't even have that for a lot of the stuff. So then he waited 24 hours and he had lost two-thirds of what he had memorized, right? So translate this into the real world.

There are some things that are caveats that we do better in the real world I would say at the big things, the gist of what we encounter, but the details we lose, most of them, most of the details of your life will be gone. And this is true for even, I would argue this is even true for people with highly superior autobiographical memory, you don't know for sure, but I can tell you more about that. This is true for everyone who's been studied as far as I know. And so if that's the case, the question is not like, why am I so forgetful? It's why do we remember the first one? It's why that title did for the book. And the question is, what do you want to remember? What are the memories that you want to take with you? Whether it's memorizing things for a class like in study skills, or whether it's your kid's birthday party,

which I talk about in chapter one. These are, it's about intention is what I say. It's the difference between attention, which can be grabbed by anything, versus intention, which is saying, this is what I want to take with me, right? Let's hover on that. Attention versus intention.

We hear these words all the time. Attention is the directing of one's perception to particular sensations or things in one environment is the way it loosely defined. Accurate but not exhaustive. Intention is understanding why we're having a cognitive sense, maybe a cognitive emotional sense of why I am directing my perception to particular things. Is that right? Yes.

It is directing your attention based on some reason that's an internal goal, right? And that's where the prefrontal cortex really comes in. So it's very easy in some ways to pay attention to me if I'm like gesticulating and I'm talking very loudly because it's grabbing your attention constantly. I mean, let's face it. I know lots of people in my life who hate this because I'm so loud and gesticulatory. You're not loud.

Who are these people giving you this feedback? Send me their names and numbers. I have words for them. And listen, I would say, given that you run a world-class laboratory, you're successful in your family life, you're successfully raising your second doll, you've written a spectacular book,

you're going on podcasts, you're educating the public, I would say you're doing great. So keep going. And whoever these people are, we'll have words with them. I need like, Homan's like words of encouragement on my phone that I could just open up. Plus your- I don't want to take us off track,

but you know, I spend a lot of time each morning. I first do a non-sleep deep rest or some sort of meditation. Rick Rubin taught me this to get into intention. And there are other people who have come into my life recently. This notion of intention, the reason I said let's hover on it is so important.

Because we are in a world where things will grab our attention, especially on social media. It's basically a war for attention. I don't think it's an attention economy anymore, or Simon's brilliant, you know, I'm not trying to take anything away from that, but it's a war for attention. And one of the ways that you rob your competitors

is by taking their attention. I used to joke when I was in a very competitive area as a postdoc, I was competing against a big lab at Harvard and this and that, which trying to find genetic markers for retinal neurons, et cetera. And I said, if I could just get them excited about The Wire, remember that show, The Wire? Because it'll suck like 15 hours of those postdocs time.

So I thought, you know, it'd be really diabolical. I didn't do it, but you know, telling people like, you have to see The Wire, they, you know, this and that, you know, because you get someone on a really good Netflix program, and if they're a competitor, you just got a competitive advantage. But this is being done all day long, right?

In any case, attention is our ability to, for our perception to be drawn to whatever is most moving, most loudest, most salient, intention is different. Yeah, and this is by the way, this isn't a technical term, this is just, I like it because it rhymes and a friend of mine came up with it. So, but yes, intention is your ability to say, this is what's important to me right now,

and that's why I need to pay attention to it. Hence the values list. Hence the values list, because if I don't keep that in mind, so we tend to think of control as being just like willpower or like you want to do the right thing or whatever. It's not. It's really a big, there's so many parts of it really,

but a big part of it is motivation. And motivation is not a trivial thing. It's not simply wanting to do the right thing, but being able to keep that value in mind and retrieve that value. Motivation is not a trivial thing. It's not simply wanting to do the right thing, but being able to keep that value in mind and retrieve that value, because everything has a value associated with, right? And sometimes things that are, you know,

I'm thirsty and there's water in front of me, that has a big value and that should grab my attention. So it's not that having your attention shift, you want it to be flexible, but you wanna to keep these higher order goals in mind. And so it's this balance between stability and flexibility. Now the key is, or let's get to your specific example of like technology, right?

So ever since I got a phone, that is a smartphone, my first iPhone. When was that? Mine was 2010. Mine was, well, you did better than me, I think. Maybe it was around the same. iPhone 3, I think, was my first. OK. We'll have to look up the iPhone.

I think I had the iPhone 3, which was whenever that came out. So until then, I would check email when I was at a computer. When I'm not, I don't think about it. Now, it's always there. And you get alerts on your phone, right? So let's play this out now. We're having this great conversation.

Let's say we leave, we talk about skateboarding and punk rock and like, yes, why didn't we talk about this on the podcast? We're having a great conversation, right? But now let's say I didn't put my phone on focus mode and I start getting all these little beeps on my phone. I know people. I know I played in a band with somebody who had ADHD and he would – anytime we were in a conversation, he would just check his text messages.

Sometimes he would text in front of me, right? So what happens is every time you do that, you're essentially shifting your task. Your mindset changes. Your intention is somewhat changed by this new task. So now I've shifted and there's a cost associated with that. In fact, actually people who study this, there's like four or five different costs that go on. It makes you slower to do the new thing.

Now I go back to the conversation. Well, now I have another cost associated with that. And so I'm not there where you are in this moment. I'm several seconds behind you and I'm still catching up while you're talking and that requires even more control to get caught up and get back up to speed. So I'm straining my natural resources. I'm straining my natural resources. I'm straining my cognitive control by shifting back and forth. But here's an even worse part of it.

So a memory, we haven't even talked about this, but it's like a lot of our forgetting happens because we have these blurry memories. They're not distinctive. They don't, you don't get a population of neurons that shouts out loud, hey, that's this conversation I had with Andy, right? It's like, it's just kind of this blurry sense of I talk to someone on a podcast.

Not saying that this will happen now because it won't. So I have this blurry memory. Well, why does that happen? Well, part of it is you have to catch the distinctive moments of these events and you have to associate them together into this cohesive narrative. One of the things we found in our research and other people have found is when, let's say if you're watching a movie and somebody changes the topic of conversation or a character comes in, something that shifts your attentional focus and shifts your understanding of what's

going on, you see this big peak in activation in the hippocampus. And what that seems to be related to is encoding a memory for what happened up to that point. And so we call that an event boundary. And so once you have an event boundary, it turns out you, like you go on to the next event and you have trouble remembering the stuff that happened right before the event battery. It's why people end up in the kitchen and they're like, what was my reason for coming here? And it's because they pass through three different rooms and their sense of where they

were was changing, their mental context updated to the point where now they have to work to figure it out, right? So this is what's happening when we are shifting between different tasks. I'm texting and I'm emailing and then I'm talking to you. Or as you've probably seen in going to conferences, people, scientists, scientists who know better are sitting typing emails while someone is giving, I've done this because I'm attentionally impaired.

Or I'm impaired, actually ADHD is a cognitive control issue I think, but nonetheless, it's like I do this, right? So it's like, I get it nonetheless, it's like I do this, right? So it's like I get it. But it's like you are now creating this fragments of memories where it's not I have a cohesive conversation. I have a little bit. I got a little bit more.

I got a little bit more. And those fragments of memory don't play together well in memory. They can compete with each other. And that competition is a big part of forgetting. And so that's why it's super important to just do one thing and then do another. If you want to do social media, fine, do it. Then do whatever it is you are supposed to do for work, right? But it's the shifting that really kills you because it creates saps your cognitive control it

Actually creates these fragmented memories. It also actually increases stress levels. So there's all sorts of you know things I know there's a lot of tech bros who are just like, oh no, I multitask. I'm great I hear not well, so I you know I'm from the Bay Area and spend a lot of time with those folks men and women in tech I think that the best ones, like the truly exceptional ones, are very good at dropping into a trench of attention. They're very disciplined with their phone use.

And the ones that are doing a lot of task switching often don't have complete lives. They really don't. They're not taking care of their health also, and they are sort of under the sense that they're working all the time when they're not. As a graduate student, I didn't have a smartphone. I did something recently.

I tweeted about this. You may have commented about it. I don't know, but this has helped me a lot. I took an old phone and I put social media on the old phone and only social media. So it doesn't operate as a phone. I can airdrop things to it. So I use that for looking at social media and for posting.

That phone is in a box. And then my main phone is for texting and other forms of communication. So I still have that distraction around me, but social media is now a dedicated thing that I spend a specific amount of time, and I have a timer on that phone. So I allocate myself a certain amount of time each day

So for every moment, I'm gonna start that timer. Yeah, once it hits zero That's it and I'm starting to shorten that amount of time the impact on productivity in terms of writing in terms of Researching in terms of just dropping into conversation. It has been enormous with that simple switch And I just find it easier to just segregate social media from the phone. Part of the problem is that the phone is,

it's like in a walking office. It's not even, it's a phone, it's a computer, it's a, I mean, it's just too much access. Well, and here's the thing, and this is really gets back to this idea of engineering your environment. And because so much of our lives we're out of control even though we feel like we're in control, right?

And it's really, if I have a higher order goal, sometimes you have to do exactly what you did, which is hack your environment to enable you to regain control, right? So what I mean by this is it's like, I, even though I might not check my phone, I might have alerts off, if I have a habit, I'm thinking about it. And every time I think about it, that urge pops into mind, I'm getting a little distracted, I'm losing a little bit of executive control. So you don't even have to do it, right? You can just think about it.

So and multitasking is just one thing. There's other things. Like one thing is, I talk about in the book is taking pictures. So you've probably been to concerts, I know I have, where it's like, you know, people are like just filming the whole things on their phone. Or like now you see the rise of Instagram walls

where you go into places and there's a wall that exists, so people can post to Instagram. Nothing wrong with this, but most, not all the research, interestingly, and I can get into why, shows that taking pictures actually impoverishes people's memory. Really? Yeah.

What about looking at pictures of, I think it was Larry Squire, when I was down at San Diego, that said that hanging a few pictures in your office of things that are really pleasant memories can really enhance your work environment because you look at them and go, I remember that. I think like because of all the context it brings about,

but you're saying that the act of taking pictures depletes our memory for that experience. Well, let me be more specific about this, right? So let's say I'm mindlessly taking pictures. So I go in, I'm seeing the Grand Canyon, I'm just like, ch-ch-ch-ch-ch. A lot of people, like intuitively on average, will say that they will remember it better

because they took pictures. But what often happens is they're not really focusing on the distinctive elements of their experience. They're just grabbing as much stuff as they can, right? Let's take the concert as another example. If you are filming the concert and you're just trying to grab what's being sung, you will have a recording of the concert.

But what's the memory you want to have? Do you want to have a memory of the song that you already can stream anytime? Or do you want the memory of how you felt, the friends you were with, the connection that you had with the artist because you were there? I know this sounds real hippie-dippie, but it's real in the sense that this is what you want to remember. I think, at least I don't want to lecture people if they want to remember taking pictures of things. That's fine. I'm sure everybody remembers taking pictures at these things.

But what did you take a picture of? And so you can use the phone, and this is where the studies show good effects, is if I mindfully use the phone and I say like, there's something here that will be a good cue that will remind me later of this great conversation. I focus the camera on that. I take a picture mindfully. I use the camera not as a way of spreading my attention and just grabbing everything in this shotgun approach,

but rather use it to find what's distinctive and what's important and actually focus me on it. That's a really good thing. So what I try to do is selectively document, not over document. I'll take a picture of people laughing or people eating. I like to go to conferences now. John Listman used to do this, late John Listman, and so he passed away. So now I try to do this.

I think more about these things. So I try to take pictures of people randomly, you know, they're drinking a beer and then they spit out laughing or something like that. And these are not things that are like landmarks, they're not things that are tourists, but they are great retrieval cues. And so what happens is the next part of it is seeing the picture. Well, what do you do when you see the picture, right? Do you scroll, right?

Or do you use it as a cue to effectively test yourself, to recall what happened during that event and integrate it? Now what's interesting is that act of recollecting the event in itself will change the memory. And it can make it more accessible, but it can also make it a little bit more abstract and story-like. And so there is an interesting trade-off where you have these things where you have these memories, and you can even document it But if you use the if the more you retrieve it the more accessible it will be But sometimes it'll be less immersive and more like a story that you've told a hundred times So is it so it sounds like if we have we go on and

On a vacation or to a show or something that taking a photo as long as it's intentional of something specific that will look, the key is to look at it later, not just post it, but to look at it later and to spend a few moments or more drawing to mind some of the emotional and cognitive experiences around that memory. That, however, changes the memory, right? Anytime we create a story, we're changing the memory.

But perhaps provided it was a good experience, that's better than to not access the photo at all. But I'm struck by, as you are, the number of people who are taking photos at a concert. A friend of mine who's a very successful photographer who shoots a lot of photos of musicians thinks this is the craziest thing. As if any one of those photos is going to be meaningful,

right, that they're outside of the experience of the concert, which is exactly what you're describing. Maybe you just have a memory of taking a lot of photos. Yeah, yeah, that's exactly what happens. People will remember something, but it's not their feeling, it's not like the friends they were with and what they talked about. It's more like the friends they were with and what they talked about. You know, it's more like, you know, I use this example in an interview.

So apologies if people have already seen this. But it's like I just I got to see the descendants. I'm guessing since you skateboarded, you probably had heard the band. The descendants. The band Milo. Yeah, yeah, yeah. Exactly. So I grew up listening to them in high school, but I never got to see them because all the great bands I got into broke up right before Black Flag and the Minutemen and so forth.

And so when they reunited, I was like – I had an opportunity to see them in a club in Sacramento. And so I saw them for the first time and what was – I wasn't one of the kids taking photos. I was actually watching. But then there was a moment where Bill Stevenson, the drummer, who's a super intense guy and really one of the creative forces behind the band, he gets up and he starts walking towards the crowd and Milo's like, sit down, go back behind the drums.

And he's like, no, I want to say something. And I was like, I got to take a picture of this because this is going to be like he's really connecting with us. And he talked about how cool it was to just be able to have this moment where he's now at this age able to appreciate this connection that he has with the audience that he couldn't appreciate before he was younger. And I was like, I'm taking a picture of this because that's what I want to remember. You won't remember everything, but if I look at that photo, technically I haven't

looked at that photo again, but just taking the picture of it forced me to really think about that. And that's the biggest takeaway I have. You know, a lot of the songs they played, they did a really good job on, but what I really took away from that was this connection that I really wanted when I was a kid, you know, and re-experiencing that feeling of being a kid and hearing these songs when they were fresh and new for me. And so that's, I know I'm sounding like kind of a hippie or something.

That's not my style. Not a hippie, you sound like a punk rocker. It's not confusing the two. That's good. Yeah, exactly. I like to agree. I got a digressing all over the place. No, no, I have a question that I'm hoping

binds some of this together related to taking photos and memories. I keep many photos, I like printed photos, I have these in a drawer, they mean very much to me. Some of them are in the studio, but I keep most of them in a drawer at home. Polaroids are an interesting example, I think, of what you're describing.

The act of taking a Polaroid is more than just clicking or pressing with your thumb on a camera. There's a waiting process, there's a, you actually get to see the photo emerge over time. I would bet, even though I haven't run the study, I would bet that people keep Polaroids more than they, and look at Polaroids more than they keep other photos. Which if you think about it is,

if it's true, if it's true, is counter logic because, you know, usually people want to do another photo because they don't like the way they looked in the previous photo. With Polaroids, you can't do too many of those. It's kind of one and done, maybe two and done. But I feel like the act of taking the Polaroid,

waiting for the photo to emerge, kind of stamps it in your memory of the experience itself. And the act of taking the photo is more involved. It's more of a process than just a click. That then you see the photo later. Now, of course, with digital photography, you see it, but you can take a hundred, you can take two two photos like that.

If we were to export this theme of limiting our task switching as a way to enhance our memory, setting up our environment in a way where we put our phone away perhaps, and we also are focused on intention, why we are in something, do you think that there's something positively reinforcing

about getting into a trench as I call it? Because I find that conversations like this, one of the reasons I do this podcast, the solo episodes and these interviews is that they provide something that my life prior to it did not provide, which was depth. I mean, we're just here. There's no phones here.

And if there are, they're off, right? And I feel like anytime we go into these trenches, could be a video game, could be an interaction with a loved one of various kinds. But when we go into these tunnels of attention, there's something that's so deeply satisfying about it, especially to those who have attention deficit issues, that it feels like something real happened

and the rest is just noise. Is there any relationship of the focus system to release of dopamine? I know release of dopamine can drive focus, but is the reverse also true? That if you're in a state of focus, do you enhance the release of dopamine can drive focus, but is the reverse also true? That if you're in a state of focus, do you enhance the release of dopamine? Correct.

That's the question. Yeah. Well, I don't know. I wish I could give you an answer and say, I don't know. And it would be really hard to disentangle the chicken and the egg, right? Because if you're measuring dopamine activity, you'd have to, well, okay.

So here's what I can say, is that I think that we often think of, you know, we think of like, let's say an emotion, right? Or any other mental state. And we think of it like it just happens. But in fact, there's a time scale to these things, right? So it's like, there is a basic response that you get when somebody points a gun at you, but then there's an interpretation that you have

that can take that threat response and make it into something more. And then you're like really jacking up your neuroadrenergic activity, right? You could test her rising. Yeah, but it's like, I mean, well, in that case, it could be a catastrophe. But if you survive, you averted the catastrophe,

the question is, does the potential catastrophe live within you or does it die within you? You only need to live within you sufficiently enough that you avoid the threat in the future, right? But that's the double-edged sword of noradrenergic systems is that they capture lots of memory and they open up thoughts about what could have gone wrong.

Yeah. But if it didn't go wrong, it didn't go wrong. You're alive. You only need to remember to avoid whatever puts you in that circumstance. Yeah, but that can still be scary, right? Sure. And this is where I think it's like this,

we talked about this before, this appraisal is very important. In the case of focus, it's a little bit different, but just to make this very concrete, the prefrontal cortex has top-down inputs to many of the neuromodulatory systems. So on average, people tend to think of the neuromodulatory systems like dopamine

and norepinephrine as being very bottom-up. They just send signals everywhere and set the brain into focus or not focus or whatever. But the prefrontal cortex has some anatomically at least some capability of regulating those systems both directly and indirectly. And so that does I think speak to this idea that if you have a very strong goal focus, you can in fact regulate the dopamine system. I think it's a and nor a norapinephrine to nor adrenergic system So I think it's a reasonable thing and I bet you Amy Arnston has done some related work on this topic

I'll check it out earlier You mentioned and I want to make sure that we return to this notion of taking care of one's vision and one's hearing as a way to offset memory loss. Very important concepts. Could you share with us what's known about that? This is just starting to be a thing, but the effect sizes, for instance, for hearing aids are really strong,

both in reducing AD risk, I believe, and in Alzheimer's risk and in just good cognitive aging and risk keeping your memory as you get older. So don't listen to your headphones too loud, right? Well, actually, okay, so speaking of things I did to preserve my brain health, I'm playing in a band now and we're pretty damn loud. And so I went to an audiologist and I got a custom earplugs.

Oh yeah, all the top music, I'm friends with some really amazing musicians. They all wear insert earplugs. Oh yeah. All the top music, I'm friends with some really amazing musicians, they all wear insert earplugs. Oh yeah, yeah, but I think these custom ones will be more effective at both preserving the spectrum of all the frequencies. Well, I just mean, protect your hearing. Yeah, yeah, yeah.

No, but yeah, but they're related because if you can't hear your frequencies, you might end up turning up and you get this paradoxical thing. Sure. So too much information, I know. But basically that is, yeah. So there is this issue with, in fact, actually there's an article that the Shersaie sent me on in the Lancet that one of their public health recommendations is to get into a preventative

mode for preventing Alzheimer's disease. And one of the things they say is, screen for hearing and give people hearing aids and make people use them if they have, encourage people to use them. Vision is starting to be a big one. People who are older get cataracts, get it treated, you know. A lot of this preventative healthcare,

which our system is not really equipped for it, but it can really save so much money, it can save so much emotional pain for so many people. It's really amazing. Another one I mentioned briefly is oral hygiene. Gum disease, it turns out, increases your risk for I believe it's Alzheimer's and also for cognitive brain health in general.

I did an episode on oral health and the effects on, as you said, on brain health are amazing because streptococcus mutans, which is the bacteria that causes cavities, can funnel its way into the bloodstream and potentially cross the blood-brain barrier, which is, I think, why people think it might be detrimental to brain health.

Yeah, yeah, I mean, I don't know the detailed mechanisms, but I think that makes sense. And there's this vague notion of cognitive reserve, which is basically, some people seem to be quite immune to vague notion of cognitive reserve which is basically some people seem to be quite immune to the effects of cognitive aging and some people seem to be very protected against Alzheimer's. So what is it? One of the things that seems to come up as far as depleting cognitive reserve or putting

it at high risk seems to be inflammation, right? Neuroinflammation and so Kim McAllister as know, was doing work on this topic of neuroimmune interactions. And basically, the immune system expresses itself in the brain. You get microglia activation that can cause these inflammatory responses. And there's reasonable evidence suggests that it's interacting with tau and amyloid

in this kind of cascade of stuff that happens in Alzheimer's disease, right? And one of the things that we're learning now, and we don't know nearly enough, but the data out there is quite scary, in fact, is long COVID is associated with significant cognitive effects. And brain, is that the explanation for the brain fog that people report? Well, it's- Many, many months in-

So they report a subjective brain fog, and you can see this, you can measure this as a significant cognitive deficit that they're experiencing, right? And we've seen in the past, like HIV, was there was actually a whole variety of dementia that was associated with HIV from the viral transmission. We can, like you can see with multiple sclerosis where you have like autoimmune responses

in the brain affect mental function dramatically. We're seeing more and more evidence of this. So this is again another one of those things. It's like you'll go, oh, COVID, I don't care about it, blah, blah, blah. I mean this is a health thing that can really affect people and it can – I don't think anybody – it's not a political issue to get brain fog, it just sucks, right? Nobody wants this. So I think there's a lot we're learning about viruses and bacteria.

One of the cool things I was talking about before we started recording is I was at a conference and I met the coolest guy and I'm blanking on his name but I'll send it to you after. But he's, he did this great study and he was studying the effects of nutrition on brain health and memory, especially cognition. And so he said, what's the most interesting finding that you've gotten? I love to ask people this because I'm curious and it stimulates my curiosity and I usually get a good answer.

So he told me he did this study where he has these rats and he gives them sugary water During the day about the equivalent. He said to a can of coke a day So they're getting this sugar when they reach adulthood, you know These teenage rats they reach adulthood and they have memory problems and they do they have hippocampal atrophy So you go? Okay. Well the hippocampus is affected, memory is affected, sugar, blah, blah, blah, no problem. So then what he does is he takes the gut bacteria from the sugar animals and puts it in an animal that doesn't get this diet.

And he finds the same kind of pathology and the same kind of memory deficit in these animals. So there's something about that process of like the gut-brain interaction that also seems to be playing a part in ways that I don't understand. I think they're still figuring it out. But again, this really shows this tight neuroimmune link. We're seeing this now with pollution. Air pollution is a big factor. So even if people don't believe in global warming, there's nothing good about being

in a place with a lot of smoke in the air. It definitely can, and this is one of the risk factors that is noted in the Lancet Report for Alzheimer's disease. One of my colleagues, Pam Lyon, is doing research on this at UC Davis showing that you get, like she actually takes real pollution from the Caldecott Tunnel, which connects Oakland and- Walnut Creek. Yeah. Yeah. And finds that rats exposed to this pollution have hippocampal damage. And so there's so many of these environmental factors that can

trigger the inflammatory response. We talked about blood sugar. Blood sugar also seems to be related to these issues. So, and diabetes is like so bad in so many ways. It's associated with those white matter hyperintensities that we talked about. And so that's bad. We've done some research on that. But it also affects – it can cause little – if you get severe diabetic ketoacidosis,

you can actually have hippocampal damage from that directly and it also dramatically increases Alzheimer's risk. We have an epidemic of diabetes right now. Matthew Feeney This probably explains, at least to my mind, why these lifestyle factors like improved sleep, cardiovascular and resistance training exercise, but certainly cardiovascular exercise, eating a lot of leafy foods, et cetera. We know all of those things offset inflammation to some degree or another, right?

I mean, one of the best ways to inflame your brain and body is to not get enough sleep and eat a lot of highly processed foods, for instance. To date, are there any even semi satisfactory prescription drugs or other compounds that can slow the progression of Alzheimer's dementia once it's started? There are now some drugs that are,

I think they're targeting amyloid that are producing some modest effects in stalling the progression of the disease. See, the problem with Alzheimer's, as you know, is once you lose neurons, you're not getting them back, right? And it's like, yeah, there's neurogenesis and you can run around, but it's not much. It's not, you don't want to, if you're depending on that, you're hosed, you know?

So, like, but getting back to the exercise thing, it's neuroprotective. And so, like, let's say with a drug, right? I mean, everybody wants a drug. If I told you, I give you this drug, you're 60 years old, and it's going to have some terrible side effects, you're going to get diarrhea, nausea, all this stuff, but it'll reduce your risk of Alzheimer's by 40%. A lot of people would be motivated to take it. Now I tell you, okay, well, here's a lifestyle intervention that's going to involve what Sarah Madden calls down states. It doesn't have to, we can actually get into that and memory reactivation

during down states, but, um, uh, involves sleep, diet, exercise, social stimulation. Right. And these things, by the way, also reinforce each other. Having better sleep makes it easier to exercise. Having exercise makes it easier, better to sleep. All of these improve mood, right? So these will improve your mental function, your

mood, as well as your mental function relatively soon and reduce your risk by at least 40 percent if not more. If you go to, I can send you this Lancet article, but it's like the amount, the proportion of variance, meaning the degree of risk that you can reduce with fully preventable or fully in our control lifestyle issues is huge. It's as big or bigger than the genetics. So- I think people really need to hear and internalize that

because I think everyone's waiting for this miracle drug that is unlikely to ever arrive, frankly. I mean, you know, to date we have some okay treatments for Parkinson's to try and offset the loss of dopaminergic neurons, but they can even transplant essentially dopaminergic neurons into the substantia nigra. But none of those things, L-DOPA, et cetera, have proved to be cures for Parkinson's. Not getting hit in the head is helpful.

Oh yeah, yeah. Traumatic brain injury is another one of the big risk factors. So there are a lot of don'ts. I'm grateful that today you're sharing a number of dos and both in the context of offsetting age-related cognitive decline Alzheimer's, but also in terms of how to enhance focus and enhance memory. I want to make sure that we touch on a few topics

related to memory that are a little bit off the trajectory we're on now, but that come up a lot when people start thinking about memory. And one that's kind of intriguing, very intriguing is deja vu. Do we have any understanding about what deja vu is? Is it just like a recollection of something similar

that spontaneously gets triggered? What is deja vu? Well, it's not fully understood, but I'll give you my best guess that's science-based and not just my wildly speculating completely. But basically, one of the early findings that gave you sense about what deja vu is, is Hewlings-Jackson, who is this great neurologist who did pioneering work in behavioral neurology, observed that many patients who get epilepsy would have this aura, it's this mental sensations

right before a seizure where they would get an intense feeling of deja vu. It doesn't happen in everyone but a certain number. This is associated with temporal lobe epilepsy and the hippocampus as you know is in the temporal lobe. But there's also these areas around it that are super important for memory, including the amygdala, but also really the perirhinal cortex is a key, key player in this. And so then you have Wilder Penfield and other people who started to do these surgeries for epilepsy,

and they said, well, I wanna make sure I'm not taking out good brain, right? You don't wanna, so Penfield wasn't responsible for HM and that was like kind of an irresponsible surgery. HM is a now dead famous patient and literally chapter in the history of neuroscience that somebody who had his hippocampi bilaterally, one on each side of the brain, removed to treat epilepsy,

it fixed the brain, removed to treat epilepsy, fixed the epilepsy, but he had lost all capacity to remember prior events. Yeah. And so, in fact, he had this dense, dense amnesia, right? And actually, one of the little known things, even in memory research, is he actually lost, he had what's called a temporal lobectomy where they just hack off the front part of the temporal lobe or it might have been cauterized. I can't remember the – I think he cauterized it.

But anyway, they do that temporal lobectomy and he actually had the posterior one-third of his hippocampus but he had lost his perirhinal cortex bilaterally. And that turned out to be Betsy Murray at NIH later and other people turned out to be a huge thing. So one of the reasons I think that he became so densely amnestic is that it was bilateral. So if you think about the brain, like you have a side of the brain that's causing a seizure, so you kind of got a spare tire on the other side where it's like that other healthy tissue on the other side can sometimes pick up the slack.

But if you take out both hemispheres now you're in really bad shape. So Scoville did that. He actually did it for people who are HM had epilepsy and it was a legit operation in that sense but he did it for people who had I think like psychosis, too, depression. I mean back then they just did all kinds of crazy stuff. So, but Penfield was like, no, I want to make sure I take out only the tissue that needs to go. So what do you do? You stimulate different parts of the brain and you see, does it produce anything other than a seizure? And if so, that's not an area you want to remove. And

so he would go into the anterior temporal lobes and stimulate and people would have, sometimes they would have an intense people would have, sometimes they would have an intense real memory. But sometimes they would have this intense sense of deja vu where it's like they feel this I feel like I've lived out this whole thing that's happening right now. I've lived it before. When you know that's not true, right? So what is this?

Well, a number of people, my lab was heavily involved with this and Andy Anelinas at UC Davis was really central to a lot of the stuff, found that the perirhinal cortex, which is this area as I said, it's a big player with the hippocampus, seems to be very critical for this general sense of familiarity that we have. And so, you know, I use in the book an example of like, if I say, have you eaten a rambutan before? Now you being a worldly guy might... Have you ever eaten a rambutan? No, I don't know what that is. Okay. So how quick was it that you were able to say no, that you were able to think about it and go, I've never

eaten a rambutan? Less than a second. Okay. So you didn't have to search your entire memory for whether or not you've eaten a rambutan, you know, because it's so unfamiliar, right? So things that are highly familiar, like, you know, maybe I'll ask if you've eaten a banana before, or grapes before, you can say yes, because, and partly you don't have to remember any instance. It just feels right, you know, those are very familiar things to you. Have you ever seen a grape before? Yes, of course you have, right? Apple, very familiar to people. So we just have that general fluency and you can look at this like I've you go into the grocery store and you see someone and you're like, I know I've seen this person before

Where have I seen them before and then you leave and eventually you're like, oh well That was somebody who I met at this conference or something like that. But you weren't expecting them at this context and no episodic memory is triggered. But there was something about their features that felt very fluent and natural to you and triggered that sense of familiarity. And that seems to be processed and you can see brain activity associated with that in the perirhinal cortex.

And people with damage to the perirhinal cortex seem to not differentiate between the rambutan and the banana. It's all kind of unfamiliar to them. They might remember I've eaten a banana, but they don't necessarily have that sense of familiarity. And Rebecca Burwell at Brown University is the coolest experiment that doesn't nearly get you know how in science you get these unsung hero experiment well what if this was one of them where she stimulated in

rats the perironal cortex at this frequency called the beta frequency which is kind of a relatively low frequency oscillation, and basically put two objects in front of the animal. And so like typically if there's a new object, the animal will spend more time like exploring it, right? And depending on how she timed the stimulation, she could make the animal think that a familiar object was novel. She stimulates at a different frequency, I think it was gamma,

and the animal now thinks of, or actually it was like, yeah, so she thinks, now the animal thinks that a familiar thing is novel. With beta, it was that it thought a novel thing was familiar. Wow. So, it could literally use this stimulation to change the way the animal is interacting with and presumably a memory driven way with this object. So for those looking for novelty in different domains of life, maybe this is the solution. Maybe. Yeah. And so, Anne Cleary, just to close the loop here, who's a great researcher at Colorado State, developed this beautiful paradigm where what she

does is she said, okay, well, does that relate to deja vu well let's see so what she did was use virtual reality and so in virtual reality you can create these environments and you know put objects in particular places and so she creates these virtual environments where there are particular objects in particular places and let's say one's a museum right so a person can go through passively and watch a movie or they actively navigate through passively and watch a movie or they actively navigate through these spaces. And then what she does is she has them go through, let's say, a video arcade.

But unbeknownst to the subject, the objects that are in the room are in exactly the same positions as the objects in the museum. But it's a video arcade, so it looks different. But the room shape, the spatial layout, you know, everything is identical. It's got a different skin on it so to speak for video gamers. So what happens is people are much more

likely, very likely, to produce a deja vu sensation when they're in these places, these virtual environments that look very much like where they've been, but they're mismatching in some critical way. So it's like you've got enough to trigger the strong sense of familiarity, but the mismatch is suppressing recollection. And so that seems to be a crucial part of why you get this uncanny feeling of remembering

is the strong familiarity you get. And by the way, I've watched these movies and I cannot for the life of me see that the museum is the same as the arcade. It just feels so different cognitively. But, you know, I can imagine being like if I really did it immersively, having that sense of familiarity. So you're really pitting these things in opposition to each other. So what likely happens with deja vu is something uncanny that triggers a little bit of memory retrieval or a strong fluency,

but then there's a mismatch that suppresses it and prevents that context from coming up. I'd like to talk about the relationship between memory and mental health for the following reason. I'm very struck by the fact that in experiments such as the work that Carl Dyseroff, who was actually the first guest on this podcast, brilliant neuroengineer, of course, and psychiatrist,

described in which he's talking to a patient who's depressed. This patient has a stimulator for the vagus nerve. They can crank up stimulation of the vagus nerve. And essentially the narrative goes from this patient, I believe it was a woman in this case, talking about being suicidally depressed. She can't anticipate doing anything of any interest

or excitement to her, increasing vagal stimulation, which by the way, folks, does not just calm people down. Vagal stimulation actually creates a lot of alertness. So this is a vast misconception out there that vagal stimulation is all about calming. In any case, as the vagal stimulation goes up, her narrative literally changes in real time to, yeah, I could see myself going out and applying for a job.

I'm kind of excited about the future, et cetera. So complete transformation of one's outlook, but also in some instances, memory of prior events. So how we cast prior events is so interesting. And the bridge I'd like to build right now conceptually is that there are two papers that intrigue me. One is a paper from Lombardo Maffei's lab in Pisa, which had a paradigm for exploring learned helplessness

in rodents, which is a sort of a model for depression, how long a rodent is willing to swim in water to save its life, right? Before it gives up. And there's a learned helplessness that eventually arrives these yes or not kind experiments. But at some point they give up and then they've essentially learned they're helpless.

And of course they save the animal before it dies. But these animals given a essentially an SSRI like Prozac can restore some sense of hope, meaning they'll swim longer after having learned to be helpless. Okay, is it recovery of depression? We don't know, but in humans, you see some of the same thing

when SSRIs have been effective and they're not always effective. You also see this in some of the psilocybin trials where people have done the psilocybin therapies. Yeah, we got to talk about that. In the correct context. And now all of a sudden people have this completely different emotional version of the same events.

Like, yep, a bunch of terrible things happened or with the MDMA trials for PTSD, controversial right now, FDA didn't approve it, but a good number of patients described saying, yeah, this really terrible set of things that happened, those happened, but I accepted and I'm taking the lessons and I'm moving on and then there's maybe even forgiveness, et cetera, but I accept it and I'm taking the lessons and I'm moving on. And then there's maybe even forgiveness, et cetera, et

cetera. So to me, this is a, this is a shift in memory brought about by a dramatic shift in neuromodulators SSRIs, of course, increased serotonin, psilocybin increases serotonin. And it's interesting to me that MDMA while it increases dopamine, most dramatically increases serotonin, seven X or more in terms of the,

now I'm not suggesting anyone do these drugs at all. You could blow out the serotonergic system with too much of it. With too much of. Too much MDA, MA. Although the studies on this is interesting because the study that claimed that MDMA did that actually was retracted.

Oh, is that right? It turns out they had inadvertently used methamphetamine. Oh, jeez. Keep in mind folks that MDMA did that actually was retracted. Oh, is that right? It turns out they had inadvertently used methamphetamine. Oh, geez. Keep in mind folks that MDMA is methylene dioxymethamphetamine. So I'm not suggesting anyone do these drugs. I'm using this as a conceptual template. Yeah, yeah, yeah.

I mean, this is abuse we're talking about too. Yeah, right, right, right. It's not like- Right, right. I mean, so in clinical trials, it's clearly been shown both for SSRIs as well as for psilocybin. These are still emerging clinical trials,

and MDMA that in a significant percentage of individuals, especially when combined with therapy, people can now feel differently about the same memory. So feeling different about the same memory and feeling different about therefore the sense of possibility going forward. This to me is incredible. And it speaks to the fact that much of depression,

the lack of a positive anticipation about the future, et cetera, is based on memories about failures of past or harms of past. Yeah, rumination basically. Right. So what is the relationship between the serotonin system and memory? Or what is the relationship more broadly

of these neuromodulatory systems or the vagal system that can create these incredible reversals of what we previously thought of as terrible, as manageable, and therefore we're willing to lean into life again. What is that? Again, serotonin's like a neuromodulator. It enhances plasticity.

And what I mean by that is that if you have like a transient learning event, you will get a change in the connections between neurons that were active during that event. And super interesting work right now going on in behavioral time scale plasticity and all that stuff. So it's not just cells that wire together, it's more interesting actually, or fire together, wire together, it's more interesting. But those changes can often be transient and what people, so like Eric Kandel, for instance,

one who studied serotonin in particular, and emphasized this, but basically many neuromodulators, if you give a little bath, bathe these neurons in serotonin or other neuromodulators, if you give a little bath, bathe these neurons in serotonin or other neuromodulators, you stabilize that plasticity and that allows increases in receptor density between these neurons that allow them to communicate more effectively. Now you can get weakening in LTD too, we won't get into that, but serotonin definitely promotes plasticity, right? And so one of the things I talk about in my book is that memories are, we all have plasticity. As I said, retrieving a memory can allow us to change the memory in certain ways.

When you get into the details of it, it becomes complicated in interesting ways. But the short version is you can change it. We get a small part of what happened when we remember. But there's that feeling of the context. There's that emotional response that we have that's both kind of a basic, raw motivational, my heart's racing or something like that. That's why people often say, well, emotional memories are stored in the body. Well, it's just part of the memory.

It's a retrieval cue, so to speak. And it can be also be part of the retrieved experience. But you have all of these factors going on that are part of this emotional memory. And then you have a story that you create, a narrative that you use to make sense of it. And that affects all these physiological systems too, right? So every time I use, I talk in the book about an example of how group therapy is so powerful as a means of memory updating, social interactions,

where it's like people can change the narrative. They say, well, you know, I gave you this narrative about how I'm loud, and you told me, well, I remember hanging out with you, and you weren't loud then, and you're not loud now, and so now I can update these memories maybe. Vigacious. Yeah, exactly, I can update these memories maybe. Visacious. Yeah, exactly. I could reframe it, right? And these framing effects are huge. So in theory,

people can take an experience that was traumatic, and many people do, and say, this made me who I am, and I'm happy with who I am now, even though it's a horrible thing, I'm stronger for it, or I'm a survivor, or, you know, I couldn't have done anything about it and it's not my fault. Or you can have these narratives of shame and so forth, and guilt, and anger, and so forth. I'm not judging anybody's reaction to trauma, but what I am saying is that's part of the emotional response It's part of the memory that people construct

The problem is is that with traumatic memories when they do stick it's hard to change Because there's so much plasticity driven by the neuromodulators during that event with PTSD Even we could talk about that as a whole nother thing, but just let's take traumatic memories. It's so intense and the amygdala response drives the physiology in many cases of that arousal which makes you feel like this immediacy of it, right? And in fact sleep and nightmares, all of a sudden. But anyway, stay out of PTSD for a moment because that's a whole other thing. But those memories are very resistant because of that intensity and often the more you retrieve them we re-traumatize ourselves.

So reframing in a cognitive therapy sense is very difficult because they feel this and their brain is telling them I'm under threat or I'm ashamed because they've reinforced this narrative so many times and you can work through the logic but sometimes you need to create some big prediction error to generate some error driven learning or something we can talk about or you need some kind of help. So if you're driving neuromodulatory systems, like that theoretically could give you a broader window of plasticity. In fact, actually, we're trying Prozac on my dog.

One of the things that I've seen … Why? She's very anxious and very like … and it's to the point where she'll not exercise, even though she's a very active dog. She'll stop on a walk if she hears a garbage truck anywhere. And so it's very low dose and I'm not necessarily saying go drug your dogs. But I'm just saying that the story that I've heard is that you get this period of plasticity where you can kind of rewrite some of these behavioral patterns and make them more open

to training and so forth. So it doesn't even have to be a permanent thing, right? And I think a lot of these things like you're talking about with learned helplessness studies probably transient effects of not being on it for years or something. But it's not very effective in terms of SSRIs. But psilocybin and psychedelics have shown a lot of promises being bigger effects, right? And these produce massive plasticity. There's two things I think that are really interesting about it. of promises being bigger effects, right? And these produce massive plasticity.

There's two things I think that are really interesting about it. So my neighbor, Dave, by the way, Davis, I will just say, I'm biased, but it's one of the top three places in the world for learning and memory research. So next door to David Olson, it turns out, is studying psychedelic effects on plasticity. And so he really emphasizes that there's these massive neurotrophic factors, BDNF, like all these factors that are going on that are promoting plasticity. And for people who've taken them, that's what they report, is that there's this period of integration afterwards where your brain's just like, you can feel it. Everything's good.

You change. You change, yeah. You change if the change, yeah. You change. If the integration is guided properly. One thing that I do want to make sure I highlight and it's not just for, you know, public safety reasons, although that as well is that people are so intrigued by the idea of quote unquote, opening plasticity.

Plasticity is just an opportunity for learning new contingencies. Yeah. Right. Just taking psychedelics is an experience, but certainly, but the learning of new contingencies occurs in the integration phase, as well as within the session. That's why the clinical trials that showed some efficacy for some people were guided intensely by therapists.

The mere act of having plasticity, plasticity is an opportunity for learning. It's not the actual learning. That's right. It opens up like significant opportunities for reshaping. But the second part of it, which maybe I think is really interesting is there is also a dissociative element of these drugs. So ketamine isn't a psychedelic, but I think there are some interesting plasticity effects and definitely produces this dissociative element too. But with psychedelics, there's often a major perspective shift. And perspective is hugely important for memory because a lot of our sense of the emotional impact of our memory

is based on a perspective that we adopt when we remember. And research has shown that you can take the same encoding event, meaning like I tell you a story, let's just take a very simple thing, a very, you know, I give you a story and it's like I tell you now viewed from the perspective of someone else and you're trying to remember it, you can remember things that you didn't remember the first time around. Changing your perspective can literally change what you remember.

It can also change the narrative that you produce. So now let's say you pull up this traumatic memory but you're viewing it from the outside and you're feeling your heart's racing, your eyes are dilating, there's these crazy effects from psychedelic, but you're seeing it and it's not you. There's some deeper self you're feeling,

whether it's true or not. Or you have a sense of agency in there. Yeah. Some of the psychedelics, I've never tried this one, but there are interesting studies of Ibogaine, Ebola, where the universal experiences I understand is that it's 22 hours long. It's actually a cardiovascular risk,

there's some things that need to be offset there, so don't run out and do this folks, but people I'm told get a high definition movie of specific events in their life that actually happened, only when they close their eyes, so no hallucinating with eyes open, interesting, and then they have agency within those movies, and once they exact the change they wanted to have it rotates like a cube very interesting perhaps to a memory researcher why this would be and

Then they get another event of past where they have agency in that event Incredible it's I mean, you know, there's so much that we don't know and I think it's you know And I will say that some of the psychedelic stuff is overhyped and there's not, some of the science is quite bad in that field right now. A number of papers are being retracted now. Yeah. Yeah, I do think that some of the concerns they had in the FDA

I take issue with. But what I will say is that you have a drug that dramatically increases plasticity, but it changes dramatically the mental context that you have when you pull up the memory. So you have a real opportunity for memory updating. Now there's a phenomenon in the animal literature called reconsolidation, where essentially the act

of retrieving a memory opens it up to requiring some kinds of neuromodulators again to really promote resealing of the memory, so to speak. But it can also, if you interrupt it, you can erase the memories. And theoretically, if you can do that, you could also change the memories pretty significantly. So if I can vividly access some neural population that's giving me this, normally gives me this physiological response that sets off this train of thoughts and it's associated with this physical and mental context, and I can dramatically, I can access those neurons but dramatically reshape the context and dramatically reshape

the narrative, I've created the opportunity for massive change. I don't know if that's true, but it sure makes sense to me that that's the case. Now having said that, if you and me share our traumatic elements of our childhood, I'm sure we could go out for drinks and do this for quite a few hours, right? That in and of itself will also produce some change in our memories. It's very powerful. And I saw this in the clinic where I was doing group therapy with Vietnam vets. And I'm like, I'm a total fraud. I'm like, I don't know, 27 years old, 28 years old. And I'm like in with these like, you know, Vietnam vets in their 50s who've really seen stuff,

you know, and they live in combat zones now in Chicago. And what I realized was everyone was telling their story, but they're hearing reflections of their story from me, but also from other members of the group who they can relate to that are different from their narrative. And now all of a sudden, what happens is the memory is no longer theirs. It's a collective memory that's shared by all these people because the memory now incorporates elements

of their reactions as well. It allows people to remember it in a new context, right? And I mean, and we can just take a much more watered down version of this where how many times have you had a terrible experience and it became a great story? I basically say that there's no point in having a bad experience in life if you don't get a great story out of it, right? So I talk in the book about a near-death experience I had paddle boarding and everything about this was stupid. It's like the degree, I could send you pictures of it and you'd be like, oh my God, what was he thinking?

I've made foolish errors in outdoor adventures in my past where afterwards I thought that was a really dumb move to even go to that location to dive, let alone what we did when we did there. Like, you know, I mean, some of the stupid stuff that we did, even as kids, like bridge jumps and without testing water depth, I mean, stupid, stupid stuff

that I don't recommend anyone repeat. But you're right, the surviving stories, you carry those forward. Yeah, yeah, exactly, exactly. The problem is the other stories we can talk about, people who are paralyzed, dead, et cetera, those stories exist too. Yeah, yeah, and well, so, I mean, to be clear,

it's like I felt horrible during that experience, and it was one of the most immediately fear-inducing experiences I've had. But later, me and Randy O'Reilly, the computational neuroscience, we're friends. We both did the stupid thing together. We would tell the story, tag team it. And, you know, we told it to students and friends and so forth.

And it just became funny. And so each time we told it, it just became kind of funnier and funnier. And you start to embellish things and so forth. And so that change of perspective was really drawn out by sharing and seeing people laugh and see people like, what were you thinking? You're such a smart person and you did this and, and it becomes part of the narrative and you know, keep in mind, there are people who do this, that they say like, I've had a really traumatic experience, but I've learned from them.

I've had a horrible, emotionally abusive relationship, but I've learned from it, right? And I don't mean to trivialize anybody's experience who didn't have that thing and they're just traumatized by it and they carry it with them. But what I am saying is that the memory, so to speak, I think in neuroscience right now there's a big hot topic about N-gram grams as if a bunch of neurons is the memory. But every time we have a memory, we're painting a new picture. We're creating a new novel. Well, and I think this is where people have to be very careful not to cowboy post-traumatic stress disorder treatment in a way that allows the narrative to make it worse because people, previous guest on this

podcast has this notion of, in describing this, of story fondling where people can go further and further into the description of how terrible something is, reinforced by others and then the memory changes to become much worse than either the real events were or just simply worse within their body and mind, and then they have to live that forward. So it can go both ways, which is really points to the key,

which is to do this with really trained professionals. Yeah, yeah, and it's all about, because you can re-traumatize yourself, and this is also why rumination is so bad in depression, is because you recall a negative memory, and that gets you in a negative mood because you pull up the contacts and then that makes it easier to recall more negative memories and then every time you recall them, now they're getting more power because they're

associated with these negative moods. Trevor Burrus So recollection is really a double-edged blade. David Kopel Oh, yeah. Yeah. I mean look at like – so if you take something like reminiscence or nostalgia. So the original term nostalgia, I credit Felipe de Brigard for, he's a philosopher neuroscientist.

He told me that nostalgia used to be a term for disease that was coined by a Swiss physician. And he used it to talk about a kind of post-traumatic experience that soldiers had, where they would get so wistful about their home that it just made them miserable in the places that they were at. It's been referred to as the pain of an old wound. Yeah, yeah, yeah, exactly. I didn't say that someone else. Yeah, yeah. And so it can, the research shows it can have very positive effects on mental health, right?

And it can have positive effects on mental health if you use that as a way of saying, hey, this is just a great thing that's happened. I'm grateful for that. But it can become toxic if you're like, my life used to be so great and now it's terrible. Even if it's positive reminiscence, if you come into it with the wrong attributions, it can become negative, toxic, and it can contaminate your present, right? I mean, the past has got good and it's got bad in it, just like the present has got good and it's got bad in it. And it's really all about what are the narratives you're constructing for it in many ways. And that plays a big part in the dynamic, malleable,

constantly shape-shifting nature of memory. Incredible. I want to make sure that we talk about something at first glance very different than all of this, but it lands squarely in the conversation we've had until now, which is your love for and your participation in rock and roll. You have a band, right?

Pavlov's Dogs. Yep, actually I have a couple bands now, I think, please. Okay, what are the other ones called? Well, so Pavlov's Dogs, I'll say, versus like a band of neuroscientists and psychology, neuroscientists and psychologists, neuroscientists who met actually, most of us met at a memory meeting, actually.

And so we get together at conferences and we'll rent out a club and we'll play basically, Brad calls it skinny tie music. It's like- Is it original music or covers? Covers, that one's a cover band. Covers, okay. And so we'll play like the Ramones, the Clash Gang of Four.

Great. It's a lot of, we added Blondie and... She's still touring. Yeah, she's amazing, isn't she? A friend of mine went on tour with her. Yeah, there's a band called Surfboard. Surfboard was on tour with Blondie. Oh, sir, I know them.

Yeah. Oh, that's a friend of yours. Yeah, Danny from Surfboard, yeah, great band, and she toured with Blondie. Oh sir, I know them. Yeah. Oh, that's a friend of yours. Yeah, Danny from Surfboard. Yeah, that great band. And she toured with Blondie. Blondie's amazing. She's still super vivacious as a surfboard and Danny. What instrument do you play?

I play guitar and I also do vocals. Lead vocals? Yes, or yeah. And- Reluctant, because sometimes it's talking or being off key, but yeah. Can people find links to any Pavlov dog live shows or recordings online?

I think we have some recordings on YouTube. And if you look on our Facebook page, maybe our Instagram too, we have live recordings. Okay, and you have a show coming up. We'll put a link to that, because people will listen to this long after that, presumably, that's coming up in Chicago on October. I think it's the seventh, is it a month?

It's the Monday. We'll put a link to that. Yeah, yeah, yeah, sorry. But for those that can't make it, because most of us aren't in Chicago, including me, unfortunately, we'll keep an eye out for Pavlov's dogs. I love that you play music, and I just have, for sake of time,

one question about your love for rock and roll and playing music. When you're playing rock and roll live, are you thinking about anything else? Sometimes and that's when I suck. Actually, you know, one thing, one hack that I came up with cause it's like with the cover band, we practice like, we cram. It's the worst thing.

It's not space learning. It's like we go through the songs and we keep adding and taking away songs, but it's like we'll cram for like, I don't know, about eight hours of practices over three days or something. And so for me, it's like a constant memory thing, because my brain doesn't want to play covers. It wants to play the songs that I've written.

And so there's always this very thing. And then I get nervous. I get really nervous. And so I move a lot, and then I'll see friends. And that kills me, because then I start thinking, what are they thinking? And so I started my last show I did with Pavlov's dogs. I wore sunglasses, and it was great.

Because then I wasn't attuned to them and I was, it just goes back to what we're talking about kind of with the camera and stuff. I was feeling it and I was thinking, I was, I was not, I was in the flow in the zone and feeling it and doing it and not thinking about it. And there's a whole interesting literature choking under pressure that actually relates to this idea of like, you know, sometimes having too much cognitive control going on is like really bad When you're under stress, and if you know something fairly well, you're gonna be better off if you just go into an automatic state I love that when I do live shows. I like to have the House lights relatively dim. I don't want to see anybody at first and then as they get more comfortable

I'm happy to have the house lights come. Oh, what do you play? I didn't know you play. I don't want to see anybody at first. And then as they get more comfortable, I'm happy to have the house lights come up. Oh, what do you play? I didn't know you play. Oh, I don't play anything. I do live events where I talk about science. Oh, yeah, yeah. Where I tell stories about science and scientists. Okay, a couple of things are right in the front of my mind

and I'd be remiss if I didn't say them right now. First of all, it's absolutely clear that we need to get you back here for more discussion about memory and learning. There's just so much that we didn't have the opportunity to cover in this conversation, but we most certainly will in a future conversation. We didn't bring up the turkeys of Davis.

Not the turkeys, no we didn't. Second of all, I want to thank you for writing your book, Why We Remember, because it's a fantastic exploration of the modern understanding of memory. Still some of the mysteries that remain, but this is a field that's evolved a lot and you capture so much of the incredible findings there

over the years in a very pleasurable way. So it's a pleasure to read. And then I also want to thank you for coming here today to share with us your understanding about memory and also your sharing of your experience with ADHD and some of the tools you use, some of the struggles. I think all too often people hear about these, you know, scientists or physicians or people who are authorities

on a topic and they don't hear about the challenges they face and I assure you that a great, great many people will appreciate the fact that you yourself have struggled with certain issues related to attention, but that you've overcome them at least as well to be able to be a functional parent and family man, professor, author, now public educator, dog owner, second time around.

And for that and for a great many other reasons, you've educated us and you've given us a great many practical tools. It's also great to see you as a fellow punk rocker and old friend. And I even let you call me Andy. So thank you. So thanks for coming here today

and please do come back again, Charn. Oh, I would love to. Thank you, Andrew. It's just been great to be here. Thank you for joining me for today's discussion about memory and ADHD with Dr. Charan Ranganath. To learn more about his work and to find a link to his book as well as social media accounts,

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