Daniel and Kelly’s Extraordinary Universe - How Does Memory Work? (Featuring Dr. Michael Yassa)

Episode Date: April 17, 2025

Kelly talks to Dr. Michael Yassa about how memories are formed, comparing brains to computers, brain-computer interfaces, and more! See omnystudio.com/listener for privacy information....

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Starting point is 00:00:00 This is an I-Heart podcast. It's important that we just reassure people that they're not alone, and there is help out there. The Good Stuff podcast, Season 2, takes a deep look into One Tribe Foundation, a nonprofit fighting suicide in the veteran community. September is National Suicide Prevention Month, so join host Jacob and Ashley Schick as they bring you to the front lines of One Tribe's mission. One Tribe saved my life twice. Welcome to Season 2 of The Good Stuff. Listen to the Good Stuff podcast on the Iheart radio app, Apple Podcasts, or wherever you get your podcast. Do we really need another podcast with a condescending finance brof trying to tell us how to spend our own money?
Starting point is 00:00:40 No thank you. Instead, check out Brown Ambition. Each week, I, your host, Mandy Money, gives you real talk, real advice with a heavy dose of I feel uses. Like on Fridays when I take your questions for the BAQA. Whether you're trying to invest for your future, navigate a toxic workplace, I got you. Listen to Brown Ambition on the I Heart Radio app, Apple Podcast, or wherever you get your podcast. I'm Dr. Scott Barry Kaufman, host of the Psychology Podcast. Here's a clip from an upcoming conversation about how to be a better you. When you think about emotion regulation,
Starting point is 00:01:14 you're not going to choose an adaptive strategy which is more effortful to use unless you think there's a good outcome. Avoidance is easier. Ignoring is easier. Denials is easier. Complex problem solving takes effort. Listen to the psychology podcast on the Iheart radio app, Apple Podcasts, or wherever you get your podcasts. Hi, it's Honey German, and I'm back with season two of my podcast. Grazacios, come again. We got you when it comes to the latest in music and entertainment with interviews with
Starting point is 00:01:43 some of your favorite Latin artists and celebrities. You didn't have to audition? No, I didn't audition. I haven't audition in like over 25 years. Oh, wow. That's a real G-talk right there. Oh, yeah. We'll talk about all that's viral and true.
Starting point is 00:01:56 trending with a little bit of cheesement and a whole lot of laughs. And of course, the great bevras you've come to expect. Listen to the new season of Dacias Come Again on the IHeartRadio app, Apple Podcasts, or wherever you get your podcast. The analogy that I like to use for this is imagine you are at a club and there's lots and lots of noise going on, lots of things going on, lots of people talking to each other. there's loud music and so on and you're trying to communicate something to somebody who's you know dancing alongside you and it's very very difficult because of all of that noise but now you get real close to them and you kind of you know hold your hand to their ears and you start to talk directly into their ears now they're going to receive that communication with much
Starting point is 00:02:44 higher fidelity be able to tune out noise and selectively attend to that communication you've enhanced the communication between that person and the person they're talking to that's what happens synapses. There's lots and lots of synaptic firing, lots and lots of communication happening. But when cells start to attach to each other, they communicate much more preferentially, they can transmit signals that express that form of learning. In other words, if there's an experience that happens that is learned by the brain, the brain can express a form of plasticity or form of memory in the strength of the connections. So if the connections grow stronger, That's a signal that this memory has been learned.
Starting point is 00:03:24 And most of the information that we have about this comes from animal models, comes from slice recordings, where we can see evidence for enhancements in the connectivity, enhancement of the communication between cells as a result of a learning experience. You've reminded me why I hate clubs. That's all right. No one invites me to them anymore. I share that with you too. Hi, I'm Daniel.
Starting point is 00:03:58 I'm a particle physicist, and every day I rely more on my computer's memory instead of my own. Yeah, I'm Kelly Weider-Smith. I'm a biologist, and I'm having a lot more of those moments where you walk into a room and think, why am I in here? I walk around campus here at UC Irvine, and a lot of folks go, hey, Professor Whiteson. And I go, hey, and I think, I have no. idea who you are and why we know each other. And sometimes it's just because they were in a class I taught with 400 people and the relationship is a little asymmetrical. And sometimes it's just
Starting point is 00:04:31 because my memory is terrible. And maybe we had coffee and I've forgotten. So I apologize to all folks out there who I'm pretending to recognize. Yep. Yep. Nope. I'm there also. And every once in while I'll be standing in the grocery store and I'll stand in front of the aisle for a little too long and my daughter will go, you forgot. Didn't you? Yeah. I have no idea what I'm looking for right now. And hopefully this doesn't give us too much anxiety thinking about what the root cause of our memory problems are. I have that as well. Is that a memory issue or is that a distraction issue?
Starting point is 00:05:03 Like where you're looking for capers, but then you see a jar of pickles and it makes you think about that last time you had a pickle. And then you're like, hmm, I wonder if you can pickle at home. And then five minutes later, you're dreaming about a whole pickling building in your backyard and you've forgotten that you were looking for capers. So I don't like pickles. So no, that's not my scenario. But sometimes it'll be like, you know, I see my reflection in a bottle and I'll be like, oh, is that spot skin cancer?
Starting point is 00:05:26 When am I going to die? There we go. Yeah, exactly. But so it is often distraction instead of forgetfulness. But, you know, sometimes it's hard to disentangle those things. Well, I've just learned something deeply troubling about you that you don't like pickles. What? You know, Daniel, you've made a really great point about your memory because we have definitely talked about this.
Starting point is 00:05:46 Oh, no. Oh, no. And I think even on the show, we've talked about this. That's embarrassing, but not as embarrassing as being close-minded to the wonderful world of pickles. I'm with you, like the big deal of pickle. Okay with the sandwich, but I'm not munching on one in general. But if you've ever done home pickling, you know, like you can pickle cauliflower or carrots, it's really wonderful. The only pickled item I've ever enjoyed is cowboy candy, which is when you slice up really hot jalapenos and put them in like a sugar pickle.
Starting point is 00:06:17 Oh, so good. That I love on sandwiches. Other than that, I have not met a pickle that I liked. I'm sorry. We're going to have to work on that. All right. Okay. All right.
Starting point is 00:06:24 Well, I'll keep my mind open. But today, we got a wonderful question from our listener, Simon, who is interested in memory. And so let's go ahead and listen to Simon's question now. Hi, Daniel and Kelly. This is Simon from New York. I was a huge fan of Daniel and Jorge Explain the Universe. However, I am loving the new show with Kelly and never miss an episode. Here is my question.
Starting point is 00:06:49 mainly for Kelly. I am now into my 70s, and not surprisingly, find myself reflecting a lot on my life and the thousands, perhaps millions of memories that go into a lifetime. I have often wondered exactly how the human brain, using biological substances, chemicals, and electricity actually stores memories. I have tried to read about this, but have not found anything to satisfy my curiosity or wonder. Perhaps this blurs too much into the question of what is consciousness and sentience and is not something you want to delve into. But if you would like to tackle it, I would love to hear about what insights biology and physics have to offer. I have very recently been reading a lot about computers trying to understand
Starting point is 00:07:40 how they really work and that seems somewhat related but only somewhat. Anyway, thanks to both of you for all you do. my weeks would not be complete without listening to your podcast episodes. All right, Simon, we love your accent. We do. I grew up in New Jersey, and I miss hearing that accent more often. So that was awesome. And thank you for this fantastic question.
Starting point is 00:08:05 And we got really lucky. So folks, remember, we talked in the past about whether or not triptophan from Turkey actually makes you sleepy on Thanksgiving. And we interviewed Mark Mapstone for that. and he suggested that if we were interested in memory, we should talk to his colleague, and his colleague was willing to come on the show. So on today's show, we have Dr. Michael Yassa. He's a professor at the University of California, Irvine, where he's also the director
Starting point is 00:08:30 of the Center for the Neurobiology of Learning and Memory, and is the director of the UCI Brain Initiative. So, like, clearly the perfect person for this topic. Yes, amazing. And also, it's one more notch on my personal goal to have my. entire neighborhood on the podcast. Those of you who don't know, people at UC Irvine, many of us live in this faculty neighborhood right next to campus.
Starting point is 00:08:53 So we're all friends and neighbors and we know each other. And by now, we've had a significant fraction of that neighborhood on the podcast because when I want to know like, hey, who's an expert in flight? I'm like, oh, I know that guy who lives on the next street. And so it's a fantastic resource. That is pretty great. So let's go ahead and bring Mike on the show. But we should mention you were off telling people about your amazing research ideas.
Starting point is 00:09:15 so you were not able to join us for this interview. So I flew solo with Mike. Thanks very much for handling this while I was goofing around in the Bay Area. My pleasure. I had a blast. All right, welcome to the show. Mike. Thanks for being with us today. Thanks for having me. So what got you interested in studying memory?
Starting point is 00:09:34 Let's start by getting to know you a bit. Sure. So I don't think that I really knew much about memory when I was an undergraduate. I was fascinated by the brain just by virtue of taking a couple of classes that kind of inspired that passion, that love for everything brain-related. And one of the things that was really fascinating about it is that I felt even at the time, this was in the late 90s, that we knew next to nothing. Unlike other classes that I took where there was sort of a big body of knowledge, it felt
Starting point is 00:10:02 like with the brain, there's just so much more that we really didn't understand. So that became really fascinating as I started to dive a little bit more deeply into different aspects of how the brain functions. memory came about as one that was front of foremost, particularly because we started to see, or I started to see, that memory loss is just very devastating, unlike any other cognitive domain that if you have an attentional deficit or if you have a deficit with executive function, you know, that can be somewhat circumscribed. It's a contained kind of deficit, but memory loss was just utterly devastating. You know, seeing patients with Alzheimer's disease, seeing patients with
Starting point is 00:10:41 various forms of memory loss. That was really compelling. And I started to understand a bit more that memory is what makes us who we are. It's so fundamental to our core. It's the essence of our consciousness. Everything that we do, we do because of some experience that we've had that we've have been able to store. And it just became not just fascinating, but like entirely all-consuming. So I focused on memory from all of its aspects. One is trying to understand its fundamental in our workings. And two, trying to understand how it breaks down in a variety. of different conditions. And if we can do that, maybe we can help people. Yeah, I've got a neighbor with Alzheimer's, and it's been totally devastating for the two
Starting point is 00:11:18 of them. So, yeah. So this interview was inspired by a question that we got from the listener, and one of the things that they asked about is, does the concept of memory blur the line with consciousness and sentience? How do you view these concepts? Yeah, you know, it's interesting. There's a somewhat related question, which is, you know, you can have a computer, have memory. We talk about memory in a computing platform in a robot or robotic application, certainly when you think about chat GPT, well, that can hold on to memory for some period of time and use that to guide how it responds to the user and so on. So memory in and of itself may not be the thing that I would say as associated with sentience.
Starting point is 00:12:00 I think that it's the way that our memory works, not just as humans, but as sort of, you know, live organisms, it's not like the way that you would do it in a computer. let me elaborate. The way that memory is stored in a computer is very much, you know, one-to-one. Everything that you see and learn, you're storing with incredibly high fidelity. You try to retrieve it 20 years from now, 30 years from now, it's exactly the same. There's no degradation. But that creates a problem for a memory system and that it's more difficult to extract generalities. It's more difficult to generate knowledge based on memory. But say as a human and you're encoding memories all the time.
Starting point is 00:12:39 These memories are stored, but we know that there's blurriness of memories, there's forgetting of memories, there's all sorts of things that we tend to think of as memory problems. But in fact, one could argue that they're not bugs, they're features of this system, because memory is not intended to be a super high fidelity kind of system. It's intended to get enough information in so that you can generalize knowledge,
Starting point is 00:13:01 so you can learn from experience and be able to guide your future decision-making. So while a computer is, memory is really about storage with high fidelity. You don't want to write a file in a word and then store and then later on have an abstract version of it rather what you actually wrote. You want to have an accurate record of what you actually wrote. But for the brain, what you might want to get later on is that abstract version. It's just enough knowledge to be able to guide your future decision making. And that's the reality of how memory evolved in life organisms and maybe the thing that makes it very different from non-sensient beings is that it never really
Starting point is 00:13:35 evolved to think too much about the past. It evolved almost entirely to think about the future. So the reason why you might store something is because you want to use that knowledge to guide future decision-making to make sure that you do things that are adaptive that promotes your survival. You're not going back to the same poison as berry bush. You know, to run from a bear out in the wild as opposed to go up and say hello. Those kinds of things are based on memory equipping us to make better predictions for the future. So can we dig in a little bit more to this trade-off? So why can't you remember everything perfectly and generalize when the time is right? Yeah, so it turns out that you can mathematically and computationally model this,
Starting point is 00:14:17 and it gives you a pretty straightforward answer. And the way that it works is that if you were to encode every single experience that you have in a very high resolution, high fidelity kind of approach, then it becomes very difficult to generalize that to new situations. the representations in the brain become almost hyper-specific. They're very, very specific to those instances in which they were encoded. So being able to extract the generalities or the knowledge that you can apply to new things requires that there's enough blur, enough fuzziness across the different instances,
Starting point is 00:14:52 so you can generalize that knowledge. I'll give you an example. If I were to ask you, what is the capital of the United States? You'd have a very, very quick answer for me, which is? Washington, D.C. Exactly. Now, if I ask you, when did you first start? learn that.
Starting point is 00:15:06 No, don't know. So now, if I had asked you the day right after you first learned that, maybe in class or maybe from parents, you would have a pretty good memory for that. It's a pretty exciting thing that you just learned. But the reality is you've learned it so many times over so many different exposures. You've heard it a million times in many different settings. And what's most important is not so much the first time you heard it or the last time you heard it, but the fact that you extracted that piece of knowledge, that core piece of
Starting point is 00:15:33 knowledge out, and now that's part of your body of knowledge. So the specifics around how and when and where we encoded specific things may not be all that important from an evolutionary standpoint to hold onto as the memory for the actual knowledge is important. That's what's going to guide your future action. That's what's important to generalize the new situations. So in some ways, there's no evolutionary pressure to hold on to the specifics over time. But it is an interesting point, Like, why can't we have both? Well, you can think about it from an energetic standpoint. If you have a limited resource system, why would you invest your energy into storing the specifics
Starting point is 00:16:12 when you know you're not going to use them down the line? Yeah, no, fair enough. So you mentioned the analogy of the brain as a computer. Is there any analogy over history comparing a brain to something else that you think is a helpful analogy or the brain is just so different, it doesn't make sense to try to compare it to anything we have experience with? So that is a really interesting question. have thought about this before, and I keep coming back to the computer, that's the closest
Starting point is 00:16:38 thing. And I always tell people, I think it is possible that we will get to a point, perhaps with quantum computing and other types of things where we might be able to approximate a human brain-like functionality in a computer. To this day, we don't have that. Even with the incredible advent of AI in large language models and all of those things, still, there are certain things that human brains can do and mammalian brains in general can do that computers just are not capable of. But there is not another device out there that is capable of this level of processing that I can think of to associate with that analogy.
Starting point is 00:17:15 Particularly, I mean, I think one of the things that the brain does, don't get me wrong, like the computational kinds of things that have been built are incredible. And the amount of the minuscule amount of time that it takes for them to be able to process and provide an answer is just wild. beyond the imagination but there are still some things that brains can do that the computers can't and in particular
Starting point is 00:17:36 it has to do with the ability to extract knowledge the ability to error correct the ability to do the kinds of decision making that we do as humans that are very difficult to encapsulating the computer the ability to have emotion emotional reactions those things are still very difficult to model
Starting point is 00:17:53 while you can tell the computer all you want about what we think the human experience is we still don't understand that well enough to be able to model it in a computer. Yeah, fair enough. All right, so let's pull back to memory a little bit. Sure. So we've talked about how memory differs from sentience. Are there different kinds of memory?
Starting point is 00:18:10 And do our brain store different kinds of memories differently? Yes. And oftentimes we just say memory as like one big blanket umbrella kind of term. But it is important to know that there are different memory types, different memory systems in the brain, and they serve different functions. So let me give you a couple of examples. One type of memory, which I tend to like quite a bit, we studied quite often in my research laboratory, is what we call episodic memory, memory for episodes, memory for events that happened to us.
Starting point is 00:18:38 And we tend to kind of operationally define it as remembering what happened, where it happened, and when it happens. So whenever you have kind of like the collection or the conjunction of those three, you can label that as an episode and you have a memory for a particular episode in your life. Typically, you think about that is also the root of our autobiographical memory, our memory for autobiographical experiences, things that happen to us. But that's very different from remembering how to tie your shoelaces or how to ride a bicycle or how to do something like your tennis swing or your golf swing. You know, those kinds of things are trained in the brain very differently.
Starting point is 00:19:13 They involve very different systems. A lot of times they require more trial and error kind of learning. And they tend to be a bit less accessible to consciousness. So they're what we call sort of implicit kinds of learning. So if you look at how the brain is organized, pretty much every patch of cortex is capable of some form of memory. Another term that we typically use in neuroscience is plasticity. The idea that the brain is plastic means it's capable of change. So whenever you have experience, cells that are responding to that experience are capable of change.
Starting point is 00:19:45 And that change typically is thought of as a change in the connections and the way that cells communicate with each other. but some change that reflects a record of the experience that you had. Now, those changes happen throughout. They can happen in our visual cortex, our visual system, our auditory system. They can happen in the episodic memory systems in the brain, or they can happen in these more implicit memory kinds of systems in the brain that typically support more unconscious function, like knowing how to ride a bicycle, like knowing how to swing a golf club,
Starting point is 00:20:15 and those kinds of things. Those are stored separately. And we know this to be true because we see patients that have deficits it's in one type of memory and not another because they have maybe a focal stroke or some damage or some deficit that impacted one system and not the other. So they struggle with one type of memory that's affected
Starting point is 00:20:31 in that system, but everything else seems to be intact. And by type of memory, does that mean like category of memories, like the tennis swing and the other sort of muscle memory things? Or like I could forget high school if I had a stroke in the right place? Right. Although that's actually increasingly difficult. So typically
Starting point is 00:20:47 if there is a stroke that is focal, it might affect motor memory. It might affect memory that allows you to kind of move your hands in the right way and be able to support that kind of function. But episodic memory is this really weird thing. Initially, it does depend on key regions of the brain, one of them being the hippocampus. That's a really important region for episodic memory. But over time, memories start to become somewhat independent of the hippocampus. They start to become stored elsewhere. And that's one of the reasons why in Alzheimer's disease, where we know the hippocampus is one of the earliest regions
Starting point is 00:21:21 to degenerate. As that starts to go away, you see a loss of recent memories, things that were recently acquired, maybe weeks, months, or a couple of years before, you know, the decline started, but things from long ago, like high school, are preserved. And the reason they're preserved is that they've now been consolidated, that's sort of a technical term for, made strengthened and made resilience to loss. And that's because they're stored sort of in parallel throughout the brain. So just the focal deficit there is likely not going to wipe out those particular memories. But it's much more likely to wipe out, say, yeah, your ability to have the right swing or write a bicycle or anything like that. Those are the kinds of things that are much more fulcally stored.
Starting point is 00:22:05 Okay. And can we dig a little bit more into exactly how the brain stores memories? Is it like how do neurons connect with each other? Yeah, let's dig in. Yeah. So brain cells are very, very unique compared to other cells in the body. And provided, this is, again, I always tell my students, you know, this is true 95% of the time, according to our knowledge today, sometimes things, you know, several weeks from now, months, years, things can get revised. So this is just according to our current knowledge today, brain cells are able to communicate with one another in a way that other cells in the body are not able to. And the way that they communicate with each other is using a combination of electricity and chemistry. So the transmission of signals within a brain cell is entirely electrical.
Starting point is 00:22:52 And we can talk about that in a second. But the transmission from one cell to the next, most of the time, is chemical. It involves the release of a neurochemical that goes from one cell, binds to the other, and then initiates another electrical signal from the next cell to the next cell. So it goes really fast electrical, somewhat slower chemical, really fast electrical, somewhat slower chemical, and so on. And you have this sort of progression of communication between cells. And that's really important because these cells need to bring in signals that essentially
Starting point is 00:23:23 encode the outside world and bring that knowledge into the brain to create some sort of representation of it and then act on that. Allow us to move, allow us to avoid a threat, allow us to seek reward all of those kinds of things. So that's how the brain typically communicates. But your question is how does memory happen? there was sort of lots of answers over the years. We used to think, well, maybe it's encoded in the DNA in cells.
Starting point is 00:23:48 Maybe it's encoded in, you know, the cell size. Maybe it's encoded in the whatever else is happening to change cell shape. And the current answer is that it is much more likely to be encoded in the connections in the way that these cells communicate with one another. So let's say cell A is firing and cell B is receiving a signal from cell A. If I were to modify somehow the frequency by which cell A communicates with cell B, by making it fire more, or increase the neurotransmitter release, or increase the number of receptors on the second cell that receives that neurotransmitter,
Starting point is 00:24:25 I can make it so that the communication between those cells is enhanced. And the way that the analogy that I like to use for this is, imagine you are at a club, and there's lots and lots of noise going on, lots of things going on, lots of people talking to each other, there's loud music and so on, and you're trying to communicate something to somebody who's, you know, dancing alongside you. And it's very, very difficult because of all of that noise. But now you get real close to them and you kind of, you know, hold your hand to their ears, and you start to talk directly into their ears.
Starting point is 00:24:56 Now they're going to receive that communication with much higher fidelity, be able to tune out millies and selectively attend to that communication. You've enhanced the communication between that person and the person they're talking to. That's what happens at synapses. There's lots and lots of synaptic firing, lots and lots of communication happening. But when cells start to attach to each other, they communicate much more preferentially, they can transmit signals that express that form of learning. In other words, if there's an experience that happens that is learned by the brain, the brain
Starting point is 00:25:27 can express a form of plasticity or a form of memory in the strength of the connections. If the connections grow stronger, that's a signal that this memory has been learned. And most of the information that we have about this comes from animal models, comes from slice recordings where we can see evidence for enhancements in the connectivity, enhancement in the communication between cells as a result of a learning experience. One, you've reminded me why I hate clubs. That's all right. No one invites me to them anymore. I share that with you too.
Starting point is 00:25:58 Yeah, yeah. Okay, so we've got these connections. They get strengthened, but then it feels like there's another step between, having this connection and then having a like specific memory so you know like we're not at the point where we could even in mice and correct me if I'm wrong about this where we could like see which neurons are firing together and know they're thinking about food yeah yeah so where do we go from there so what you're talking about actually is a very very big problem that we deal with in neuroscience and in cognitive science and it's the credit assignment problem how do you know
Starting point is 00:26:29 that a particular cell is assigned to a particular memory or a particular connection It's assigned to particular memory. And it's a very challenging question. And we don't know the answer yet, but we suspect there's been a lot of research on what's called mechanisms of allocation. In other words, how can you allocate particular synapses, brain cell connections, and cells, to a particular memory and not another, right? So how can we get the specificity that we need in the system? And there's been a flurry of work in recent years, understanding that are certain proteins that are used to, quote, label. synapses, label particular cells, and assign them to one memory and not another.
Starting point is 00:27:09 It's just brilliant work by some of my colleagues in the field that has tried to really get at this specificity question. We're still early days. We don't have final answers yet. But I think we have some tentative ideas that you can with specific proteins that are expressed in the synapse, essentially label them or prime them to be the ones that are modified by this experience and maybe not another. Wow. And that's pretty cool, right?
Starting point is 00:27:32 Because for the moment of the time, we thought, well, how can we ever have any specificity in our brains? If memory just activates cells, how do you know which cells are the ones that are involved here? And this might actually apply this with some answers. Wow. I feel like I recently heard about the connectome project, which I think is trying to figure out all of the neurons. So does this suggest that once we have a connectome, next we need to work on the proteome that connects to the connectome to me to really understand how all of this works? Or how helpful is this connectome project going to be? Very helpful.
Starting point is 00:28:01 I think that every time we try to map another own, it is very helpful. At some point, we'll have an everything own. And, you know, with that sort of large-scale data effort, we're going to need also the AI, the machine learning, all of those tools. You're able to parse through it and actually figure out what's going on. But it's interesting, you know, Kelly, when I was coming up as a student, there was always this question that was asked by faculty in my department and many other departments.
Starting point is 00:28:27 And it's a theoretical question, and I want to pose that question to you. which is if we were to map every single neuron in the brain and every single connection in the brain, would we have learned anything about how the brain actually functions? And whenever they asked that question, some of us were tempted to say, yeah, of course, you're going to have all the data, right? And the answer they wanted us to get to is,
Starting point is 00:28:49 no, you're no better off because you have a ton of data but no way to really test hypotheses and understand function. You have to have the right model. You have to have the right kind of strategy to go into that data and look for what's necessary. But I would argue that over the last 20, 30 years, that thinking has evolved. And now we can go in in a completely unsupervised fashion
Starting point is 00:29:12 without having a model, which means also we avoid some of the biases that might come from a model and ask, what does the data tell us? Sure, there's an explosion of data, but there are patterns that are hidden in there. And if you train up AI enough, it can pick up on those patterns
Starting point is 00:29:27 and maybe tell us that there's a new model, There's a different model. The way that we were thinking about the brain and forming hypotheses may not have been right all along. So I go back to things like the connectome projects and trying to resolve the connectome, the proteome, the epigenome, all of those kinds of things as different layers of knowledge about the nervous system. And if we have all of that information, it stands to reason that we should be able to pick up on patterns. And patterns can maybe transform the way that we think about the brain. Maybe we're wrong all along. Maybe the brain does quantum computing, maybe all sorts of things that we just would have never imagined but are buried in that data.
Starting point is 00:30:08 It sounds like an exciting time to be in the field. Oh, absolutely. Absolutely. A foot washed up a shoe with some bones in it. They had no idea who it was. Most everything was burned up pretty good from the fire that not a whole lot was salvaged. These are the coldest of cold cases, but everything is about to change. Every case that is a cold case that has DNA right now in a backlog will be identified in our lifetime. A small lab in Texas is cracking the code on DNA. Using new scientific tools, they're finding clues in evidence so tiny you might just miss it.
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Starting point is 00:31:14 On the IHeart Radio app Apple Podcasts Or wherever you get your podcasts Hola, it's Honey German And my podcast, Grasasas Come Again, is back This season we're going even deeper Into the world of music and entertainment With raw and honest conversations with some of your favorite Latin artists and celebrities. You didn't have to audition?
Starting point is 00:31:33 No, I didn't audition. I haven't audition in like over 25 years. Oh, wow. That's a real G-talk right there. Oh, yeah. We've got some of the biggest actors, musicians, content creators, and culture shifters, sharing their real stories of failure and success. You were destined to be a start.
Starting point is 00:31:52 We talk all about what's viral and trending with a little bit of chisement, a lot of laughs and those amazing Vibras you've come to expect. And of course, we'll explore deeper topics dealing with identity, struggles, and all the issues affecting our Latin community. You feel like you get a little whitewash because you have to do the code switching? I won't say whitewash because at the end of the day, you know, I'm me.
Starting point is 00:32:13 But the whole pretending and cold, you know, it takes a toll on you. Listen to the new season of Grasasasas Come Again as part of my Cultura podcast network on the IHartRadio app, Apple Podcast, or wherever you get your podcast. Hey, sis, what if I could promise you you never had to listen to a condescending finance bro? Tell you how to manage your money again. Welcome to Brown Ambition.
Starting point is 00:32:34 This is the hard part when you pay down those credit cards. If you haven't gotten to the bottom of why you were racking up credit or turning to credit cards, you may just recreate the same problem a year from now. When you do feel like you are bleeding from these high interest rates, I would start shopping for a debt consolidation loan, starting with your local credit union, shopping around online, looking for some online lenders because they tend to have fewer fees and be more affordable. Listen, I am not here to judge. It is so expensive in these streets.
Starting point is 00:33:04 I 100% can see how in just a few months you can have this much credit card debt when it weighs on you. It's really easy to just like stick your head in the sand. It's nice and dark in the sand. Even if it's scary, it's not going to go away just because you're avoiding it. And in fact, it may get even worse. For more judgment-free money advice, listen to Brown Ambition on the IHeart Radio. app, Apple Podcast, or wherever you get your podcast. I'm Dr. Joy Harden-Brandford, and in session 421 of therapy for black girls, I sit down
Starting point is 00:33:32 with Dr. Ophia and Billy Shaka to explore how our hair connects to our identity, mental health, and the ways we heal. Because I think hair is a complex language system, right, in terms of it can tell how old you are, your marital status, where you're from, you're a spiritual belief. But I think with social media, there's like a hyperfixation and observation. of our hair, right, that this is sometimes the first thing someone sees when we make a post or a reel is how our hair is styled. We talk about the important role hairstylists play in our community, the pressure to always
Starting point is 00:34:06 look put together, and how breaking up with perfection can actually free us. Plus, if you're someone who gets anxious about flying, don't miss session 418 with Dr. Angela Neil Barnett, where we dive into managing flight anxiety. Listen to therapy for black girls on the IHeart Radio app. Apple Podcasts or wherever you get your podcast. I'm going to pull us back a little bit in our conversation. You were talking about how you can strengthen connections between neurons. Does that happen because you're thinking of the same memory over and over again?
Starting point is 00:34:44 And so how do memories get strengthened and how do we lose some of them? Yeah. So the strengthening of memory or the idea of consolidation, which is exactly what it sounds like. it's making memories more solidified or more strengthened. It can happen because we are repeatedly rehearsing the memories. We're thinking about it over and over. But the good news, Kelly, is that that happens completely incidentally without you intentionally trying to do it.
Starting point is 00:35:07 Your brain constantly brings up old memories and thinks about them. And even if you're not consciously aware of it, it happens while you sleep at night. Okay. So the brain is sort of on the back burner constantly playing through these memories and replaying through these memories. And even when you go to sleep, it's replaying through these memories. So the strengthening act of memories doesn't have to be this intentional thing, which I think
Starting point is 00:35:27 is a really powerful thing that tells students also. You don't have to sit here and regurgitate and rehearse everything over and over, just go through it, understand it, and then get a good night's sleep. Right? A lot of them really struggle to do. But during that period, you might think, well, that's just rest. Actually, the brain can be quite active during that period of time and can be playing through these memories and storing them and trying to make them more resistant to forgetting.
Starting point is 00:35:51 Now, one thing to note also is that when you replay memories, when you bring back memories, you don't end up with the same thing being stored again. So memories are reconstructed in nature. If I were to bring back an experience, say that I had from a few weeks ago, and talk about it with you, what I end up storing now and reinforcing is a somewhat altered version of that memory. It's not the same thing. Because memory is reconstructed on piecing together the pieces.
Starting point is 00:36:19 pieces just get incorporated because we're having a conversation about it. And then later on, what I remember is some amalgamation of all of those experiences when I brought it back and changed that ever so slightly. My colleague here at UC Airline, Beth Loftus, built her career on studying false memories and how they arise. And they are very, very frequent. They arise all the time. We generate them more as we get older. And they happen just by virtue of our memory being a reconstructive system rather than a high fidelity video camera or picture. picture of reality, it's just sort of a hodgepodge construction of what that reality might have been.
Starting point is 00:36:55 And again, we say, why is this happening? Why can't we have a high fidelity version of things? And it's possible that we just don't need to. So even with these false memories arising, they're very artifactual, like you really need to remember exactly what happened and where it happened or when it happened or you just need to remember the core knowledge. So if we focus on, hey, the core knowledge is being remembered accurately, that's all that matters. else can go to crap and nobody's going to be less able to survive. So from a survival
Starting point is 00:37:22 standpoint, it doesn't matter that you have this strengthening, be a very high fidelity strengthening. It just matters that the core component knowledge is the thing that's strengthened, like the capital of the United States, Washington. Everything else, who cares? But if the lawyer is, you know, priding you for details in a court case, that's when you're in some trouble. Absolutely. And, you know, the good news is, well, the somewhat good news is some lawyers, some federal judges, some jury, get the lecture about false memories and understand that when you call witnesses to stand and you're asking very, very specific questions, that their recollection is going to be some combination of what actually happens, what the brain sort of reconstructed it to be,
Starting point is 00:38:04 what kinds of questions are being asked, the pressure, any interrogation that happened earlier, all of those things sort of weave their way into that memory. You're never going to be able to get this beautiful, accurate, 100% depiction of what happens. You're going to be able to, to get some variance of it that could be quite a bit more corrupted. Gosh, there could be a whole podcast on that topic. So my co-host wanted me to dig into how we learn about this kind of stuff. So you mentioned that there are animal models, but just focusing on people right now, how good are our techniques for watching how the brain works and living humans to sort of try to get
Starting point is 00:38:41 a handle on some of this stuff? Yeah. So when we started out, the discipline of neuropsychology had very, very poor. tools available to it. So you have to develop cognitive assessments, which have come a long way. You can have the right kinds of cognitive assessments and so on. But you really have to work with patients in the clinic who come in presenting with memory problems with a variety of different conditions. And essentially, it's akin to lesion studies. You're working with patients who might have circumscribed focal deficit in the brain. You can see that on structural MRI, for example,
Starting point is 00:39:12 and say this part of the brain is damaged or missing. Therefore, they have this kind of function. So you might be able to say something about the function of this part of the brain in a healthy person. But our tools have evolved significantly since. So two major advances that I can tell you are still today the chief ways by which we study this. One is functional MRI. We tend to do a heck of a lot of that in my lab. So functional MRI operates on the principle that you can put somebody in the scanner, totally intact brain, and give them a game to play or a memory task or any sort of challenge that would engage
Starting point is 00:39:47 the memory bits of their brain, for example. And what you're imaging with functional MRI is not neural activity directly, what you're imaging is blood flow. The idea being that if there's a patch of cortex, a patch of brain that is more active, that is engaged in this challenge, it's going to require oxygen and glucose,
Starting point is 00:40:07 and it's going to try to extract that out of the blood flow. So by mapping how much oxygenated blood and deoxygenated blood are going to different areas in the brain, you can generate a contrast because it turns out that the degree of oxygenation has a different magnetic signal. So that's sort of the little hack that we pull in MRI because we're changing magnetic fields. So by measuring that contrast, we can get an indirect proxy to where neural activity might be by virtue of that blood flow change. So that's been a really, really helpful technique since the late 90s, early 2000s, in the early
Starting point is 00:40:44 days of functional MRI, people did a bunch of like really just awful studies because the technology was new and we didn't know what to do with it. And folks didn't really think beyond, you know, the X marks the spot kind of approach, right? I want to know what the fill in the blank part of the brain is. It even got as absurd as I want to know what the God part of the brain is, right? So people started to do those kinds of studies, try to go in and say, X marks the spot, where is the stuff happening? Is this the same system where they had that dead trout? Oh, yeah. You know that that child study, of course. So at the end of the day, it is a statistical approach to comparing activation.
Starting point is 00:41:21 And, yeah, that study was really compelling because you could show that you see activation essentially in something that is dead. And people every now and then will kind of make fun of this and remember the old days of fMRI when folks didn't really know what they were doing. And you could get something like this, right? And in some cases, you can even get it to be published, which is crazy when you think about it. But we've come a long way since. So the beauty of functional MRI now is that, one, we understand how to do the X marks the spot much, much better. We now have much better handle on the statistical challenges, the way to build the right contrast, the way to correct multiple comparisons, all the things that you tend to think of when you're doing large-scale statistics.
Starting point is 00:42:00 That discipline would have to kind of come to functional imaging and inform it, and that has happened, which is great. But the second part is, I told you before that memory is all about the connections, and functional MRI initially was all about blobology, right? try to find little hotspots in the brain, pretty pictures of the cover of science and all that with little hotspots in the brain and that was the approach. But we know that memory is not in the hotspots, memories in the connections. So we've started to move much more towards connectivity analysis and asking about how are the different parts of the brain communicating dynamically and essentially co-activating with each other to support solving this challenge or
Starting point is 00:42:39 doing this memory test or memory game while you're in the scanner. So, So that was the advent of functional connectivity kinds of approaches, which are, I think, far more compelling, far more robust against some of the initial critiques of a functional MRI. And they reflect the true nature of how the brain works. The brain is one big dynamical system. It's not just regions working in isolation. Everything is connecting with each other. So we owe it to ourselves to try to understand it from that much more complex way.
Starting point is 00:43:08 So functional MRI still remains a very, very powerful tool, but now the analyses that we can do are just far more advanced. The other thing that I think is just incredibly powerful aside from animal models is the ability to directly record electrical activity from cells or from what's called local field potentials that the areas around cells that have also electrical activity that can be measured directly in patients and these are typically patients that are going to undergo surgery for epileptic seizures so the surgery is done to remove the part of the brain where the seizures are
Starting point is 00:43:42 from and typically when they come into a hospital they're in a hospital for about a week or so they get implanted with electrodes to record from the parts of the brain where the clinician might suspect that epilepsy is happening and they're taken off of anti-epileptic medication and essentially they're waiting to induce a seizure and once that seizure is induced they track the location that's how they decide on where to do the surgery there's about a week or so while they're in the hospital with electrodes penetrating deep into their cortex and many of those electrodes directly into the memory bits of the brain like the hippocampus.
Starting point is 00:44:18 And those patients are just an incredible group of individuals because they also, most of them want to help science and they understand the opportunity the scientists have while they're laying in a hospital bed for about a week to understand something fundamental about the brain. So every now and then they give us the opportunity to give them a challenge, maybe on an iPad or a computer while they're laying there, and they try to solve this challenge, try to to play this memory game or do this memory test while we're recording direct electrical activity from their brain cells which is incredible so it gives us almost the same degree of information that you can get in an animal model now in an animal model in a rodent you can stick more electrons
Starting point is 00:44:57 you can get you know higher fidelity and with patients you have to do things that are only clinically warranted so there's an ethical obligation of course to make sure that nothing is being done that would ever put the patient at increased risk so that also poses some limitations as to how you can record activity and get that data. But it's just incredible access that we have to the brain in partnership with these remarkable individuals. And we've learned a heck of a lot about how the brain works and how memory works from those direct electrical recordings. Wow. I previously wrote a chapter on brain computer interfaces and I was reading about like Utah arrays. Is this the same thing or is this a different kind of electric? Yes. So Utah arrays are one way to do it. Utah arrays are
Starting point is 00:45:40 a little bit more invasive. They involve several electrons that are kind of going through the surface of the cortex at the same time. They're no longer kind of the standard practice for most patients. They're still used in some cases where they're clinically warranted, but in many cases they're not because you suspect that what's happening is deep into the brain so you stick direct single electrodes all the way down to where you suspect the action might be. And you avoid some of the potential damage that happens with utah rays. So they're used in some clinical contexts, but in many others, we can stick these much thinner, slimmer electrodes directly into the parts of the brain that we suspect the epilepsy is emanating from. So far less damage that way,
Starting point is 00:46:22 and those patients typically have better outcomes than patients implanted with Utah arrays. Your point about BCIs, and there's a number of companies out there that are trying to develop brain computer interfaces using these kinds of arrays, I think that's a particular challenge for those enterprises is how do you create a way to measure directly from the brain and to be able to stimulate and influence the brain without causing too much damage with having electrons that are thin enough that are made from the right material so that you don't cause a lot of tissue damage because ideally what you want to do is create an interface that helps people so you don't want to inadvertently cause more damage. When we were thinking about Utah rays and damage
Starting point is 00:47:01 we thought about like a cup with jello in it and you stick some needles in there And as you move the jello around, if the needles are kind of staying in place, that would sort of mess up the brain. Is that a good way to think about it? Does it all move together? Yeah, the brain certainly is as vulnerable, maybe as a cup of jello, but the key is also flexibility. So you're right. When you have these electrodes, there's a bit of a compromise. So want them to be flexible so that they're moving with the brain. You're absolutely right. That'll cause less tissue damage. But at the same time, flexibility can come out of cost, which is what they're targeting might change. So you want to make them flexible enough so that they don't cause damage, but rigid enough
Starting point is 00:47:40 so that they can continue to target the same region. So it is not an easy challenge at all. But there's been some developments recently in doing these kinds of arrays with animals. And we haven't yet ported that over to humans and done the FDA approval and all of those kinds of things. It's happening soon. There's already experiments that try to test out one of the technologies, like Neuripixel, for example, or Neopixels technologies. Those have been incredibly powerful for animal models for operating from rodents and from non-human primates.
Starting point is 00:48:10 And they're small form factor. They're thinner, but they have a ton of electrode contacts on there. So it can really give you information from a lot of different cells simultaneously. And porting that over to humans, I think, will be a really helpful thing to do. But that's only been done in some limited experiments and not widespread use. So I'm hoping that some variants of those kinds of technologies will make its way to prime time soon. I've watched some videos of people with brain computer interfaces that were able to do incredible things. But one of the things that sounded totally devastating to me was, if I understand this correctly, it's over time the brain has a response to those electrodes and like kind of walls them off and the connection gets less good.
Starting point is 00:48:47 I don't know exactly what's happening. Do we have any progress in that area? Well, so that's another thing that needs to be tackled also with some of these newer silicon probes. They're less likely to have the inflammatory and the calcification kinds of responses that happen around electrical. Because remember, this is a foreign object entering the brain. And the brain's natural disposition towards foreign objects is attack it, right? That's why we have brain's immune cells. We have microglia.
Starting point is 00:49:12 We have a lot of cells that are dedicated to detecting and eliminating foreign objects. So you tend to see them sort of aggregate around electrode contact locations and things like that. But there are ways with different substances to kind of maybe fool the brain a little bit into thinking, this is okay. You can try to also reduce the brains immune response to some extent when these things are coming in. So there's approaches that are being developed to try to get better long-term outcomes. But yeah, we're still very early in this game. And for listeners who are maybe not as familiar with brain computer interfaces, what are some reasons that people might get a brain computer interface? There's a variety of reasons. So for example, for someone who has lost the
Starting point is 00:49:51 ability to control their limbs because of a stroke or a focal deficit, being able to have a brain computer interface shortcut signals so that they can still control their limbs in their body is remarkable. And patients who have had those kinds of approaches, it is just life-changing. They go from, you know, a paraplegic or quadriplegic to being able to have use of their arms and their legs again. So there's incredible utility there. For folks who, you know, might have epilepsy, for example, that there is a brain computer interface that is a stimulator that is implanted in the brain that responds to the earliest signs of epilepsy. seizures and then is able to, with electrical stimulation, essentially knock it out.
Starting point is 00:50:32 So now instead of having to have the person be going in for surgery and lumping out parts of the brain or having them be devastated by epileptic seizures, you can have an implanted BCI that responds in a closed-loop system. So it uses the responses of the brain itself to tell the stimulator what to do, and that's a completely closed loop, so it doesn't require any user intervention from the outside. That allows it to do a much better job of helping the patient. overcome seizures or epilepsy. So there's a number of different uses. I can imagine that for movement disorders for a variety of different conditions where
Starting point is 00:51:06 you might want to implant something that communicates with the brain and feeds at the right signal at the right time, there's going to be a huge use for a BCI. Then there's a whole other class of uses that may not require implantation right so these might be external devices maybe devices that are communicating with the brain in external fashion, maybe portable or mountable, and they allow it to improve function for stroke rehabilitation or improve function
Starting point is 00:51:34 in some other way. There's a lot of folks also kind of, you know, taking the transhumanist approach here and trying to develop BCIs to just improve our function. We just want to be better at something, right? So what if I can control this robotic arm to do some, you know, whatever it is? So don't care too much about those,
Starting point is 00:51:49 but certainly the utility for helping patients is huge. So getting a little more sci-fi here, do you think we'll ever be able to know what somebody is thinking by having a cap on their head or electrodes in their brain? Or is that just way too far off? I think we already do. So I think we are to some extent with an electrocapsule, so EEG is really the technology that you're talking about.
Starting point is 00:52:14 Or there's other ways to do it also with various ultrasound technologies and so on. You can detect and stimulate pretty easily. But the problem is the kind of of things that you can get this system to do are still fairly rudimentary. So I can tell, for example, based on EG signal, whether the person is going to move their hand or make some overt kind of gesture. And motor control is a somewhat simpler system than like memory executive decision or emotion or having very complex feelings like guilt, right, or things like that are
Starting point is 00:52:48 much more difficult to capture in the simple signals that we're captured with BCI's right now. So do I anticipate that at one point we'll be able to do that 100%. There's no doubt. The technology is there. It's just a matter of, are we recording from enough? Are we able to build the sophisticated models to model this function? And we're making rapid progress in that arena. So from a sci-fi perspective, I'm sure you've heard this before,
Starting point is 00:53:13 the moving vehicle, the car was sci-fi at one point until something invented it, right? So all of these things that we think about as sci-fi are just science that's not here yet. All right. Yeah, the future is now. Hello, it's Honey German And my podcast, Grazac's Come Again, is back. This season, we're going even deeper
Starting point is 00:53:37 into the world of music and entertainment with raw and honest conversations with some of your favorite Latin artists and celebrities. You didn't have to audition? No, I didn't audition. I haven't audition in, like, over 25 years. Oh, wow. That's a real G-talk right there.
Starting point is 00:53:50 Oh, yeah. We've got some of the biggest actors, musicians, content creators and culture shifters sharing their real stories of failure and success. You were destined to be a start. We talk all about what's viral and trending with a little bit of chisement, a lot of laughs, and those amazing vivas you've come to expect.
Starting point is 00:54:12 And of course, we'll explore deeper topics dealing with identity, struggles, and all the issues affecting our Latin community. You feel like you get a little whitewash because you have to do the code switching? I won't say whitewash, because at the end of the day, you know, I'm me. Yeah.
Starting point is 00:54:25 But the whole pretending and cold, you know, it takes a toll on you. Listen to the new season of Grasas Come Again as part of My Cultura Podcast Network on the IHartRadio app, Apple Podcasts, or wherever you get your podcast. Hey, sis, what if I could promise you you never had to listen to a condescending finance, bro, tell you how to manage your money again. Welcome to Brown Ambition. This is the hard part when you pay down those credit cards. If you haven't gotten to the bottom of why you were racking up credit or turning to credit. cards, you may just recreate the same problem a year from now. When you do feel like you are bleeding from these high interest rates, I would start shopping for a debt consolidation loan,
Starting point is 00:55:02 starting with your local credit union, shopping around online, looking for some online lenders because they tend to have fewer fees and be more affordable. Listen, I am not here to judge. It is so expensive in these streets. I 100% can see how in just a few months you can have this much credit card debt when it weighs on you. It's really easy to just like stick your head. in the sand. It's nice and dark in the sand. Even if it's scary, it's not going to go away just because you're avoiding it. And in fact, it may get even worse. For more judgment-free money advice, listen to Brown Ambition on the IHeart Radio app, Apple Podcasts, or wherever you get your podcast. A foot washed up a shoe with some bones in it. They had no idea who it was.
Starting point is 00:55:43 Most everything was burned up pretty good from the fire that not a whole lot was salvageable. These are the coldest of cold cases. But everything is about to change. change. Every case that is a cold case that has DNA right now in a backlog will be identified in our lifetime. A small lab in Texas is cracking the code on DNA. Using new scientific tools, they're finding clues in evidence so tiny you might just miss it. He never thought he was going to get caught. And I just looked at my computer screen. I was just like, ah, gotcha. On America's Crime Lab, we'll learn about victims and survivors. And you'll meet the team behind the scenes at Othrum, the Houston lab that takes on the most hopeless cases to finally solve the unsolvable.
Starting point is 00:56:30 Listen to America's Crime Lab on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. I'm Dr. Joy Harden Bradford, and in session 421 of therapy for black girls, I sit down with Dr. Ophia and Billy Shaka to explore how our hair connects to our identity, mental health, and the ways we heal. Because I think hair is a complex language system, right? In terms of it can tell how old you are, your marital status, where you're from, you're a spiritual belief. But I think with social media, there's like a hyper fixation and observation of our hair, right? That this is sometimes the first thing someone sees when we make a post or a reel is how our hair is styled. You talk about the important role hairstyles play in our community, the pressure to always look put together,
Starting point is 00:57:18 and how breaking up with perfection can actually free us. Plus, if you're someone who gets anxious about flying, don't miss Session 418 with Dr. Angela Neil Barnett, where we dive into managing flight anxiety. Listen to Therapy for Black Girls on the iHeart Radio app, Apple Podcasts, or wherever you get your podcast. All right, so let's talk about losing. losing memory a little bit as we wrap things up.
Starting point is 00:57:50 So we talked about how your brain is working overnight to strengthen memories. How do we lose memories over time? So there's a number of different ways to do this. Memory can be lost because of decay. So just the passage of time, a lot of times can make memories just harder to remember, harder to access. And we've known this since 1880s. Herman Ebbinghaus was the first to kind of do this using experiments with himself.
Starting point is 00:58:16 would learn lists of nonsense syllables and then try to map his own forgetting curve. So how much forgetting happens over the first 24 hours, next 24 hours, next 24 hours. Yeah, I know. Experiments on yourself. Very, very boring times in 1880. So you didn't have too much else to do, so he did this with himself. But mapped what's called the forgetting curve, which we still, to this day, we can look at any sort of memory function or any memory test that we do in the lab, and we see a very clear
Starting point is 00:58:41 forgetting curve. A lot of forgetting the first 24 hours, then things kind of taper off. So there's that. And the suspicion is that mostly it's decay. But sometimes it happens because of interference, because similar memories get in there and kind of interfere with one another, compete with one another. So then the memory that you have for them get a little bit fuzzy. And again, these are maybe features, not bugs, right? Where maybe the system is not intending to hold onto memories with high fidelity for long. So interference and decay help us extract what's most important and keep that over time, and then other things can kind of go away. Those are natural things that happen in every brain all the time, and there's nothing to be concerned about. Decay, interferes, nothing to be concerned about. But as we get older, and by older, I hate to say this. You know, I'm talking about like 40s and above.
Starting point is 00:59:27 Oh, that's not what I wanted to hear, Mike. I hate to say that. Well, I'm going to say, gradually in our fourth decade and then maybe a little bit more precipitously over time, memory does get more difficult. So things do degrade, and we start to maybe lose to some extent our ability to make it. new memories and code new memories our memories for the old stuff is still there still resilience even though every now and then we might have a problem with access so we get distracted we lose retrieval cues but you know it's there
Starting point is 00:59:56 because if you get the right reminder boom it comes back right it's just a matter of like tip of the tongue you know being able to remember exactly that the right cue for retrieval that becomes more difficult when we're just more distracted but as we get older making new memories becomes harder and then for some folks who might go down the trajectory to Alzheimer's disease right then that becomes exceptionally more difficult that's one of the first things to go and there's a very difficult line between what's normal I hate to say that word maybe more typical age associated memory impairments which you can
Starting point is 01:00:30 expect in every brain and that's something that may be a bit more cause for concern because it may be going out about the Alzheimer's disease dissociating those two say in the 60s and 70s is actually very difficult it's not very easy Because both can start out as a form of forgetfulness, but with Alzheimer's disease or with dementia, it's very progressive. So it does get worse and worse and worse over time. That change in a healthy aging brain or a typical aging brain is far less steep. So you don't see too much changing over time. You don't see this degradation to the point where it becomes very noticeable by family, friends, neighbors, and so on.
Starting point is 01:01:07 So those are the forms of memory loss or memory change that happened. Totally innocuous, no cause for concern. They happen every day to everyone, to the best of us. And then some that are a bit more cause for concern as we get older. Mechanistically, is it just the messages are not getting sent between those cells anymore? This is something we've done quite a bit of work on, actually. Mechanistically, what seems to be the case is that first, the part of the brain that's really important for encoding these episodic memories, the hippocampus, as I said, has a very interesting change in its dynamic. So this is a massive information processing hub in the brain.
Starting point is 01:01:45 Even though it's a small structure, it carries a big information processing load. And it kind of can shift its state from encoding new information to remembering old information. And there are a few changes that happen to the cells in that system as we get older that bias the system towards remembering old information and away from encoding new information. And there's lots of sort of reasons why that is. to change the excitation inhibition balance, we tend to change neurotransmitter concentrations, all those kinds of things as we get older that cause that change in the information processing balance.
Starting point is 01:02:20 But the other thing that happens more in the context of Alzheimer's disease is you also start to deprive the hippocampus of its main input coming in from the rest of the brain. So there's a region that sits alongside the hippocampus called the antirinal cortex and that region shrivels up in Alzheimer's disease. It's one of the first regions to deposit what's called tangle pathology or tau tangles, and that's a marker of cell death. So there's massive cell loss that's happening in the enteroidal cortex early on, which deprives the hippocampus of its principal input.
Starting point is 01:02:54 So in computer science, we have this old adage called garbage in garbage out. And that's essentially what's happening in the hippocampus. It's the quality of the information that's coming in starts to become much more degraded in the context of Alzheimer's C. can't possibly expect it to do a good job in coding information and storing it with high fidelity if the information coming in is in some ways, quote, garbage. So that tends to be one of the things that is also mechanistically associated with memory loss in the aging brain. Do we know why that region starts to degrade in some people and not others? You know, there's hypotheses and I have
Starting point is 01:03:29 my pet hypotheses in the field has its pet hypotheses and so on, but there's a variety of contributors. We suspect that in the context of Alzheimer's disease, it's a combination of inflammatory changes so that the neuroimmune system is dysregulated in Alzheimer's disease where the inflammatory response that normally is very healthy, starts to kind of take a turn and become very pathological. There's vascular damage that happens as we get older, and we suspect that some of those early vascular insults, so related to blood flows, the fitting of the arteries and so on, can also contribute to that. There's metabolic regulation that changes, so the metabolic demands of different regions also becomes dysregulated as we get older.
Starting point is 01:04:10 And then one thing that we've worked quite a bit on is excitation inhibition balance. And the notion that normally the brain keeps this dynamic beautifully between stop signals and go signals. And as we get older, there actually is an overabundance of the go signals, which can drive the brain pathologically more towards memory loss. and not enough of the stop signals. So that imbalance can also be a contributor. So it's a multifactorial issue. There's lots of contributors. This is not just one single pathology kind of model
Starting point is 01:04:41 as much as some of the field likes to believe that. It's a bit more complex. So as someone who just learned that they're in the old category? I would necessarily call it that. I would just say we're maybe done developing and we're now just kind of hitting that hump of, we're going to start the aging process. Got it, got it.
Starting point is 01:04:58 I'll think of it that way, but I like that better. Fair enough. What kinds of science-based things can we do to maintain our memory? So I see all these apps pitch to me. Is there any science behind any of those things? Well, the app stuff, probably not. I will tell you the four big things that are really, really important. And when I say really important, I mean they are supported both by epidemiological data
Starting point is 01:05:21 and by clinical trials. So these things are really, really helpful. The first one is physical activity. We know that physical activity maintains brain health well into older adulthood. We know that it can delay the onset of Alzheimer's disease, it can make the outcomes better for patients, and it's protective. It really is knocking out, so sedentary lifestyle is a risk factor. We've done work also to show that even activity as brief as 10 minutes of walking can be helpful to memory. So it doesn't take a lot, you know, I would say 30 minutes of, you know, mild to moderate activity like walking, brisk walking, that's sufficient to be able to give people, you know, a way to handle that risk factor.
Starting point is 01:05:59 The second thing that's really important, and this kind of goes back to your idea about apps and kind of cognitive engagement, it turns out that apps and brain games and all of that, efficacy is a little bit tenuous, so there's conflicting reports, but we know that social engagement is really important. So in other words, if you remove social engagement, if folks become isolated as St. Past Retirement, that's a risk factor, for sure. But if they're able to continue to be social, build larger social networks in person, you know, volunteering community centers, churches, synagogues, whatever it is, or being around people in
Starting point is 01:06:32 general. And that can also combine with physical activity. So let's say it's dance class. Now it's physical activity and social contact, right? Those kinds of things. Even in interventional studies have been shown to have very positive results. Then the third piece is diet. A heart healthy diet is a brain healthy diet. And the one that has been tried and true in clinical trials is the Mediterranean diet. So the Mediterranean diet, which has lots and lots of variants, but think very colorful leafy green vegetables and so on healthy fats and reducing you know things like red meat and so on so that one also has been tried in clinical trials compared to other diets and seems to be able to stay of off risk and then the last piece which i think is one of the most important
Starting point is 01:07:15 to sleep we all need good quality and quantity of sleep every night it turns out that actually during sleep we go through a process of glymphatic clearance and we clear out a lot of the pathologies that can lead down the path to Alzheimer's, these are at least be contributors to it. And studies have shown that if you have sleep loss, folks, for example, who sleep less than six hours a night versus those who sleep more than seven or eight hours, there's differences in their amyloid uptakes.
Starting point is 01:07:42 So the amyloid pathology is one of the chief of pathologies of Alzheimer's disease. You see a lot more of it in those who sleep, those fewer hours, and a lot less of it in those who sleep longer. So sleep disruption, sleep loss, that's a risk factor. the good news is most sleep problems are treatable, whether it's because of obstructive sleep apnea or insomnia or any other reason. Restless leg, all of those things, there's good treatments out there that will help people sleep better. So those are the four sort of chief things. There's many other smaller
Starting point is 01:08:10 things, but those are the four ones that I like to lead with because they have just excellent data in their favor. Well, I'm excited about the sleep thing. I like sleeping. Maybe it's time to get out and exercise a little more. So my co-host is a physicist. He always ends on. on a question about aliens. So here we go. If an alien were to land on Earth today, do you think they would store memories in a similar way? You know, if you had asked me that question 10 years ago, I would have said, yes, I think our memory system is exceptional. It's wonderful, it's brilliant. Why not? It should be like a model to strive to achieve. But I will take the opportunity since we've got a couple more minutes, Kelly, and tell you about something that changes my
Starting point is 01:08:50 answer to this question. And that is the discovery that was made first by James McGowan. who is the founding director of my center here at UC Irvine and we continue to do work with this group of remarkable individuals who have what's called highly superior autobiographical memory we spent a lot of time during this conversation talking about how memory is fallible there's forgetting there's interference it's not meant to store everything with high fidelity because that's going to compromise your knowledge generation and so on well these folks would beg to differ and it's incredible because they do store things with high
Starting point is 01:09:23 fidelity they can remember everything that happened in their lives since they were teenagers and tell you exactly what happened on what day of the week what month and so on and they don't have a problem extracting generalities and knowledge also so sometimes they'll joke with them and say i think you're like the x-men of our generation um ex people of our generation it's remarkable and we still don't understand how they do it and how their brains are wired differently so if aliens sufficiently advanced aliens i think if they're reaching earth before we reach them they're probably far more advanced than us. They're more likely to have figured out a way to do that,
Starting point is 01:09:58 which sort of combines the best of what we have built into our computers and what we have built into our brains. Just no compromise, no sacrifice. Awesome. Well, I wish Daniel we're here to hear that, but I'm sure he'll enjoy hearing that explanation when he gets back. Thank you so much for your time, Mike. This was absolutely fascinating.
Starting point is 01:10:16 You're very welcome. I very much enjoyed it, Kelly. Thank you. Daniel and Kelly's Extraordinary Universe is produced by IHeart Radio. We would love to hear from you. We really would. We want to know what questions you have about this extraordinary universe. We want to know your thoughts on recent shows, suggestions for future shows.
Starting point is 01:10:41 If you contact us, we will get back to you. We really mean it. We answer every message. Email us at questions at Daniel and Kelly.org. Or you can find us on social media. We have accounts on X. Instagram, Blue Sky, and on all of those platforms, you can find us at D and K Universe. Don't be shy.
Starting point is 01:11:00 Write to us. I'm Dr. Scott Barry Kaufman, host of the Psychology Podcast. Here's a clip from an upcoming conversation about how to be a better you. When you think about emotion regulation, you're not going to choose an adaptive strategy which is more effortful to use unless you think there's a good outcome. Avoidance is easier. ignoring is easier, denial is easier, complex problem solving, takes effort. Listen to the psychology podcast on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts.
Starting point is 01:11:33 It's important that we just reassure people that they're not alone and there is help out there. The Good Stuff Podcast Season 2 takes a deep look into One Tribe Foundation, a non-profit fighting suicide in the veteran community. September is National Suicide Prevention Month, so join host Jacob and Ashley Schick as they bring you to the front lines of One Tribe. Tribe's mission. One tribe saved my life twice. Welcome to season two of the Good Stuff. Listen to the Good Stuff podcast on the Iheart radio app, Apple Podcasts, or wherever you get your podcast. Do we really need another podcast with a condescending finance brof trying to tell us how to spend our own money? No thank you. Instead, check out Brown Ambition. Each week, I, your host, Mandy Money, gives you real talk, real advice with a heavy dose of I feel uses. Like on Fridays when I take your questions for the BAQA. Whether you're trying to invest for your future, navigate a toxic workplace, I got you. Listen to Brown Ambition on the
Starting point is 01:12:29 IHeart Radio app, Apple Podcast, or wherever you get your podcast. Hi, it's Honey German, and I'm back with season two of my podcast. Grazias, come again. We got you when it comes to the latest in music and entertainment with interviews with some of your favorite Latin artists and celebrities.
Starting point is 01:12:45 You didn't have to audition? No, I didn't audition. I haven't auditioned in like over 25 years. Oh, wow. That's a real G-talk right there. Oh, yeah. We'll talk about all that's viral and trending with a little bit of cheesement
Starting point is 01:12:57 and a whole lot of laughs. And, of course, the great bevras you've come to expect. Listen to the new season of Dacias Come Again on the I-Heart radio app, Apple podcast, or wherever you get your podcast. This is an I-Heart podcast.

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