WEBVTT - How Does Memory Work? (Featuring Dr. Michael Yassa) 0:00:05.440 --> 0:00:07.600 The analogy that I like to use for this is 0:00:08.039 --> 0:00:11.800 imagine you are at a club and there's lots and 0:00:11.840 --> 0:00:13.640 lots of noise going on, lots of things going on, 0:00:13.680 --> 0:00:16.200 lots of people talking to each other, there's loud music 0:00:16.280 --> 0:00:19.200 and so on, and you're trying to communicate something to 0:00:19.280 --> 0:00:22.639 somebody who's dancing alongside gm, and it's very, very difficult 0:00:22.640 --> 0:00:25.400 because of all of that noise. But now you get 0:00:25.400 --> 0:00:26.759 real close to them and you kind of, you know, 0:00:26.880 --> 0:00:28.920 hold your hand to their ears and you start to 0:00:28.960 --> 0:00:31.960 talk directly into their ears. Now they're going to receive 0:00:32.000 --> 0:00:34.640 that communication with much higher fidelity, be able to tune 0:00:34.680 --> 0:00:38.440 out noise and selectively attend to that communication. You've enhanced 0:00:38.479 --> 0:00:41.479 the communication between that person and the person they're talking to. 0:00:42.120 --> 0:00:45.320 That's what happens at synapses. There's lots and lots of 0:00:45.320 --> 0:00:48.720 synoptic firing, lots and lots of communication happening. But when 0:00:48.800 --> 0:00:51.400 cells start to attach to each other, they communicate much 0:00:51.440 --> 0:00:55.680 more preferentially. They can transmit signals that express that form 0:00:55.720 --> 0:00:59.240 of learning. In other words, if there's an experience that 0:00:59.360 --> 0:01:02.160 happens that is learned by the brain, the brain can 0:01:02.240 --> 0:01:06.000 express a form of plasticity or a form of memory 0:01:06.040 --> 0:01:09.240 in the strength of the connections. So if the connections 0:01:09.240 --> 0:01:12.280 grow stronger, that's a signal that this memory has been learned. 0:01:12.840 --> 0:01:14.920 And most of the information that we have about this 0:01:15.000 --> 0:01:18.200 comes from animal models, comes from slice recordings where we 0:01:18.240 --> 0:01:22.680 can see evidence for enhancements in the connectivity, enhancement of 0:01:22.680 --> 0:01:26.720 the communication between cells as a result of a learning experience. 0:01:26.880 --> 0:01:29.959 You've reminded me why I hate clubs. I'm sorry, no 0:01:29.959 --> 0:01:31.120 one invites me to them anymore. 0:01:31.120 --> 0:01:46.320 I share that with you. Hi, I'm Daniel. 0:01:46.360 --> 0:01:49.040 I'm a particle physicist, and every day I rely more 0:01:49.080 --> 0:01:50.960 on my computer's memory instead. 0:01:50.680 --> 0:01:51.080 Of my own. 0:01:53.040 --> 0:01:55.480 Yeah, I am Kelly Leader Smith. I'm a biologist, and 0:01:55.520 --> 0:01:57.680 I'm having a lot more of those moments where you 0:01:57.720 --> 0:02:01.480 walk into a room and think why am I in here? 0:02:04.080 --> 0:02:05.920 I walk around campus here at you see Irvine and 0:02:05.960 --> 0:02:08.200 a lot of folks go hey, Professor Whitson, and I 0:02:08.240 --> 0:02:10.920 go hey, and I think I have no idea who you. 0:02:10.880 --> 0:02:12.440 Are and why we know each other. 0:02:13.000 --> 0:02:15.320 And sometimes it's just because they were in a class 0:02:15.320 --> 0:02:17.480 I taught with four hundred people, and the relationship is 0:02:17.520 --> 0:02:20.720 a little axometrical. And sometimes it's just because my memory 0:02:20.800 --> 0:02:23.480 is terrible, and maybe we hit coffee and I've forgotten, 0:02:23.600 --> 0:02:26.960 So I apologize to folks out there who I'm pretending 0:02:27.000 --> 0:02:27.880 to recognize. 0:02:28.280 --> 0:02:30.480 Yeah, yeah, no, I'm there also, And every once in 0:02:30.520 --> 0:02:32.240 a while be standing in the grocery store and I'll 0:02:32.280 --> 0:02:33.680 stand in front of the aisle for a little too 0:02:33.720 --> 0:02:37.959 long and my daughter will go, you forgot, didn't you. Yeah, 0:02:38.040 --> 0:02:40.160 I have no idea what I'm looking for right now. 0:02:40.200 --> 0:02:44.760 And hopefully this doesn't give us too much anxiety thinking 0:02:44.800 --> 0:02:47.519 about what the root cause of our memory problems are. 0:02:47.720 --> 0:02:50.000 I have that as well. Is that a memory issue 0:02:50.040 --> 0:02:52.760 or is that a distraction issue? Like where you're looking 0:02:52.880 --> 0:02:55.080 for capers, but then you see a jar pickles and 0:02:55.120 --> 0:02:56.720 it makes you think about that last time you had 0:02:56.720 --> 0:02:58.320 a pickle, and then you're like, m I wonder if 0:02:58.320 --> 0:03:00.360 you can pickle at home. And then five minutes later 0:03:00.520 --> 0:03:03.480 you're dreaming about a whole pickling building in your backyard, 0:03:03.760 --> 0:03:05.760 and you've forgotten that you were looking for capers. 0:03:06.600 --> 0:03:09.320 So I don't like pickles. So no, that's not my scenario. 0:03:09.680 --> 0:03:11.320 But sometimes it'll be like, you know, I see my 0:03:11.360 --> 0:03:13.200 reflection in a bottle, and I'll be like, oh, is 0:03:13.240 --> 0:03:15.840 that spot skin cancer? When am I gonna die. 0:03:15.800 --> 0:03:16.280 There we go? 0:03:16.400 --> 0:03:17.919 Yeah, exactly, but. 0:03:18.440 --> 0:03:22.280 It is often distraction instead of forgetfulness. But yeah, sometimes 0:03:22.320 --> 0:03:24.240 it's hard to disentangle those things. 0:03:24.440 --> 0:03:26.600 Well, I just learned something deeply troubling about you that 0:03:26.639 --> 0:03:27.760 you don't like pickles. 0:03:28.000 --> 0:03:31.440 What you know, Daniel, You've made a really great point 0:03:31.520 --> 0:03:33.880 about your memory, because we have definitely talked to about 0:03:36.800 --> 0:03:39.040 and I think even on the show, we've talked about this. 0:03:39.400 --> 0:03:43.760 That's embarrassing, but not as embarrassing as being closed minded 0:03:43.960 --> 0:03:46.240 to the wonderful world of pickles. I'm with you, like 0:03:46.240 --> 0:03:48.600 the big deal pickle, okay with the sandwich, but I'm 0:03:48.600 --> 0:03:50.600 not munching on one in general. But have you ever 0:03:50.640 --> 0:03:53.640 done home pickling, you know, like you can pickle cauliflower 0:03:53.760 --> 0:03:54.400 or carrots. 0:03:54.720 --> 0:03:55.640 It's really wonderful. 0:03:55.880 --> 0:03:59.360 The only pickled item I've ever enjoyed is Cowboy candy, 0:03:59.760 --> 0:04:02.600 which which is when you slice of really hot halopanos 0:04:02.680 --> 0:04:06.040 and put them in like a sugar pickle. Oh so good. 0:04:06.080 --> 0:04:08.200 That I love on sandwiches. Other than that, I have 0:04:08.240 --> 0:04:09.440 not met a pickle that I like. 0:04:09.840 --> 0:04:11.800 I'm sorry, I have to work on that, all right. 0:04:11.800 --> 0:04:14.160 Okay, all right, well, I'll keep my mind open. But 0:04:14.280 --> 0:04:18.280 today we got a wonderful question from our listener, Simon, 0:04:18.600 --> 0:04:21.200 who is interested in memory, and so let's go ahead 0:04:21.240 --> 0:04:22.520 and listen to Simon's question. 0:04:22.640 --> 0:04:26.920 Now, Hi, Daniel and Kelly. This is Simon from New York. 0:04:28.000 --> 0:04:30.360 I was a huge fan of Daniel and joege Explain 0:04:30.440 --> 0:04:33.039 the Universe. However, I am loving the new show with 0:04:33.160 --> 0:04:37.200 Kelly and never missed an episode. Here's my question, I 0:04:37.240 --> 0:04:41.839 think mainly for Kelly. I am now into my seventies 0:04:42.320 --> 0:04:46.719 and not surprisingly find myself reflecting a lot on my 0:04:46.839 --> 0:04:50.560 life and the thousands, perhaps millions of memories that go 0:04:50.640 --> 0:04:54.320 into a lifetime. I have often wondered exactly how the 0:04:54.400 --> 0:05:00.880 human brain, using biological substances, chemicals, and electricity, actually doors memories. 0:05:01.680 --> 0:05:04.080 I have tried to read about this, but have not 0:05:04.160 --> 0:05:09.279 found anything to satisfy my curiosity or wonder Perhaps this 0:05:09.360 --> 0:05:12.080 blurs too much into the question of what is consciousness 0:05:12.080 --> 0:05:15.559 and sentience and it's not something you want to delve into. 0:05:16.640 --> 0:05:18.680 But if you would like to tackle it, I would 0:05:18.760 --> 0:05:22.280 love to hear about what insights biology and physics have 0:05:22.400 --> 0:05:25.920 to offer. I have very recently been reading a lot 0:05:26.120 --> 0:05:30.680 about computers, trying to understand how they really work and 0:05:30.720 --> 0:05:35.640 that seems somewhat related, but only somewhat anyway, Thanks to 0:05:35.680 --> 0:05:38.279 both of you for all you do. My weeks would 0:05:38.279 --> 0:05:41.719 not be complete without listening to your podcast episodes. 0:05:42.400 --> 0:05:44.400 All right, Simon, we love your accent. 0:05:44.720 --> 0:05:45.040 We do. 0:05:45.640 --> 0:05:48.640 I grew up in New Jersey and I miss hearing 0:05:48.640 --> 0:05:51.240 that accent more often, so that was awesome, And thank 0:05:51.240 --> 0:05:54.799 you for this fantastic question. And we got really lucky. 0:05:54.800 --> 0:05:58.200 So folks, remember we talked in the past about whether 0:05:58.320 --> 0:06:00.680 or not tripped a fan from Turn he actually makes 0:06:00.720 --> 0:06:04.000 you sleepy on Thanksgiving and we interviewed Mark Mapstone for 0:06:04.040 --> 0:06:06.880 that and he suggested that if we were interested in memory, 0:06:07.080 --> 0:06:09.440 we should talk to his colleague, and his colleague was 0:06:09.480 --> 0:06:12.240 willing to come on the show. So on today's show 0:06:12.240 --> 0:06:15.120 we have doctor Michael Yassa. He's a professor at the 0:06:15.240 --> 0:06:19.400 University of California, Irvine, where he's also the director of 0:06:19.440 --> 0:06:22.800 the Center for the Neurobiology of Learning and Memory and 0:06:23.160 --> 0:06:27.000 is the director of the UCI Brain Initiative. So like 0:06:27.360 --> 0:06:29.400 clearly the perfect person for this topic. 0:06:29.760 --> 0:06:32.640 Yes, amazing, and also it's one more notch on my 0:06:32.720 --> 0:06:36.039 personal goal to have my entire neighborhood on the podcast. 0:06:36.600 --> 0:06:38.240 For those of you who don't know people that you 0:06:38.279 --> 0:06:41.080 see Irvine. Many of us live in this faculty neighborhood 0:06:41.120 --> 0:06:43.360 right next to campus, so we're all friends and neighbors 0:06:43.400 --> 0:06:45.560 and we know each other. And by now we've had 0:06:45.600 --> 0:06:49.239 a significant fraction of that neighborhood on the podcast. Because 0:06:49.440 --> 0:06:51.280 I want to know, like, hey, who's an expert flight 0:06:51.320 --> 0:06:53.080 I'm like, oh, I know that guy who's on the 0:06:53.080 --> 0:06:55.880 next street. And so it's a fantastic resource. 0:06:56.000 --> 0:06:58.120 That is pretty great. So let's go ahead and bring 0:06:58.160 --> 0:07:00.760 Mike on the show. But we should mention you were 0:07:00.880 --> 0:07:03.479 off telling people about your amazing research ideas, so you 0:07:03.520 --> 0:07:06.000 were not able to join us for this interview. So 0:07:06.279 --> 0:07:07.560 I flew solo with Mike. 0:07:07.839 --> 0:07:09.880 Thanks very much for handling this while I was goofing 0:07:09.920 --> 0:07:12.240 around in the area my pleasure. 0:07:12.280 --> 0:07:17.160 I had a blast. All right, Welcome to the show, Mike, 0:07:17.200 --> 0:07:18.320 Thanks for being with us today. 0:07:18.840 --> 0:07:19.640 Thanks for having me. 0:07:20.040 --> 0:07:22.880 So what got you interested in studying memory? Let's start 0:07:22.880 --> 0:07:23.800 by getting to know you of it? 0:07:24.640 --> 0:07:28.080 Sure, So, I don't think that I really knew much 0:07:28.120 --> 0:07:31.160 about memory when I was an undergraduate. I was fascinated 0:07:31.160 --> 0:07:33.120 by the brain just by virtue of taking a couple 0:07:33.160 --> 0:07:36.800 of classes that kind of inspired that passion, that love 0:07:36.920 --> 0:07:40.000 for everything brain related. And one of the things that 0:07:40.080 --> 0:07:42.000 was really fascinating about it is that I felt, even 0:07:42.040 --> 0:07:44.440 at the time, this was in the late nineties, that 0:07:44.520 --> 0:07:47.600 we knew next to nothing. Unlike other classes that I took, 0:07:47.640 --> 0:07:49.640 where there was sort of a big body of knowledge, 0:07:49.680 --> 0:07:52.200 it felt like with the brain, there's just so much 0:07:52.240 --> 0:07:55.960 more that we really didn't understand. So that became really fascinating. 0:07:56.000 --> 0:07:57.800 As I started to dive a little bit more deeply 0:07:57.840 --> 0:08:01.600 into different aspects of how the brain functions, memory came 0:08:01.640 --> 0:08:04.640 about as one that was front and the foremost, particularly 0:08:04.680 --> 0:08:07.160 because we started to see or I started to see 0:08:07.200 --> 0:08:11.640 that memory loss is just very devastating, unlike any other 0:08:11.880 --> 0:08:15.200 cognitive domain that if you know, if you have attentional 0:08:15.280 --> 0:08:18.680 deficit or if you have a deficit with executive function, 0:08:19.280 --> 0:08:22.600 you know, that can be somewhat circumscribed. It's a contained 0:08:22.680 --> 0:08:25.840 kind of deficit, not memory loss, which just utterly devastating, 0:08:26.320 --> 0:08:29.560 you know, seeing patients with Alzheimer's disease, seeing patients with 0:08:30.000 --> 0:08:33.160 various forms of memory loss, that was really compelling, and 0:08:33.240 --> 0:08:36.079 I started to understand a bit more that memory is 0:08:36.120 --> 0:08:38.520 what makes us who we are. It's so fundamental to 0:08:38.559 --> 0:08:41.800 our core. It's the essence of our consciousness. Everything that 0:08:41.840 --> 0:08:43.800 we do we do because of some experience that we've 0:08:43.800 --> 0:08:46.000 had that we've been able to store, and it just 0:08:46.040 --> 0:08:50.320 became not just fascinating, but like entirely all consuming. So 0:08:50.760 --> 0:08:54.000 I focused on memory from all of its aspects. One 0:08:54.080 --> 0:08:57.080 is trying to understand it's fundamental inner workings, and too 0:08:57.400 --> 0:08:59.720 trying to understand how it breaks down in a variety 0:08:59.720 --> 0:09:01.800 of differ and conditions. And if we can do that, 0:09:01.920 --> 0:09:03.400 maybe we can help people. Yeah. 0:09:03.440 --> 0:09:05.960 I've got a neighbor with Alzheimer's and it's been totally 0:09:06.000 --> 0:09:09.040 devastating for the two of them. So yeah, So this 0:09:09.160 --> 0:09:11.280 interview was inspired by a question that we got from 0:09:11.320 --> 0:09:14.120 the listener and one of the things that they asked 0:09:14.160 --> 0:09:17.120 about is does the concept of memory blur the line 0:09:17.160 --> 0:09:21.839 with consciousness and sentience? How do you view these concepts? 0:09:22.240 --> 0:09:25.160 Yeah, you know, it's interesting. There's a somewhat related question, 0:09:25.360 --> 0:09:28.680 which is, you know you can have a computer have memory. 0:09:28.760 --> 0:09:31.400 When we talked about memory and a computing platform in 0:09:31.440 --> 0:09:34.199 a robot or a botic application, certainly when you think 0:09:34.200 --> 0:09:36.760 about chat GPT, well that can hold on to memory 0:09:36.760 --> 0:09:39.600 for some period of time and use that to guide 0:09:39.720 --> 0:09:41.720 how it responds to the us there and so on. 0:09:42.240 --> 0:09:45.600 So memory in and of itself may not be the 0:09:45.640 --> 0:09:49.120 thing that I would say as associated with sentiens. I 0:09:49.160 --> 0:09:52.640 think that it's the way that our memory works, not 0:09:52.720 --> 0:09:55.480 just as humans, but as sort of you know, live organisms. 0:09:55.800 --> 0:09:57.079 It's not like the way that you would do it 0:09:57.160 --> 0:10:01.079 in a computer. So let me elaborate. Memory is stored 0:10:01.080 --> 0:10:05.000 in a computer is very much one to one. Everything 0:10:05.040 --> 0:10:09.320 that you see and learn, your storing with incredibly high fidelity. 0:10:09.440 --> 0:10:11.480 You try to retrieve it twenty years from now, thirty 0:10:11.559 --> 0:10:13.880 years from now. It's exactly to say there's no degradation. 0:10:14.320 --> 0:10:16.920 But that creates a problem for a memory system, and 0:10:17.000 --> 0:10:20.480 that it's more difficult to extract generalities. It's more difficult 0:10:20.520 --> 0:10:24.880 to generate knowledge based on memory. But say as a 0:10:24.960 --> 0:10:27.480 human and you're encoding memories all the time. These memories 0:10:27.520 --> 0:10:30.320 are stored, but we know that there's blurriness of memories, 0:10:30.360 --> 0:10:32.680 there's forgetting of memories. There's all sorts of things that 0:10:32.720 --> 0:10:36.080 we tend to think of as memory problems, but in 0:10:36.120 --> 0:10:39.360 fact one could argue they're not bugs, they're features of 0:10:39.440 --> 0:10:42.000 the system. Because memory is not intended to be a 0:10:42.040 --> 0:10:45.640 super high fidelity kind of system. It's intended to get 0:10:45.920 --> 0:10:49.160 enough information in so that you can generalize knowledge, so 0:10:49.200 --> 0:10:51.440 you can learn from experience and be able to guide 0:10:51.679 --> 0:10:55.760 your future decision making. So, while a computer's memory is 0:10:55.800 --> 0:10:58.160 really about storage, with high fidelity, you don't want to 0:10:58.360 --> 0:11:00.520 write a filin word and then store and then later 0:11:00.600 --> 0:11:02.600 on have an abstract version of it rather than what 0:11:02.640 --> 0:11:04.760 you actually wrote. You want to have an accurate record 0:11:04.760 --> 0:11:07.400 of what you actually wrote. But for the brain, what 0:11:07.480 --> 0:11:10.280 you might want to get later on is that abstract version. 0:11:10.600 --> 0:11:12.880 It's just enough knowledge to be able to guide your 0:11:12.880 --> 0:11:16.640 future decision making. And that's the reality of how memory 0:11:16.679 --> 0:11:19.000 evolved in live organisms. And maybe the thing that makes 0:11:19.040 --> 0:11:23.520 it very different from nonsensient beings is that it never 0:11:23.600 --> 0:11:27.160 really evolved to think too much about the past. It 0:11:27.280 --> 0:11:30.600 evolved almost entirely to think about the future. So the 0:11:30.679 --> 0:11:33.280 reason why you might store something is because you want 0:11:33.320 --> 0:11:36.079 to use that knowledge to guide future decision making, to 0:11:36.120 --> 0:11:38.040 make sure that you do things that are adaptive to 0:11:38.120 --> 0:11:40.480 promote your survival. You're not going back to the same 0:11:40.559 --> 0:11:42.760 poison as berry bush. You know, to run from a 0:11:42.760 --> 0:11:44.440 bear out in the wild, as supposed to go up 0:11:44.440 --> 0:11:47.920 and say Hello, those kinds of things are based on memory, 0:11:47.960 --> 0:11:50.400 equipping us to make better predictions for the future. 0:11:50.840 --> 0:11:52.640 So can we dig in a little bit more to 0:11:52.720 --> 0:11:56.959 this trade off? So why can't you remember everything perfectly 0:11:57.240 --> 0:11:59.800 and generalize when the time is right. 0:12:00.360 --> 0:12:03.320 Yeah. So it turns out that you can mathematically and 0:12:03.400 --> 0:12:07.240 computationally model this and it gives you a pretty straightforward answer. 0:12:07.280 --> 0:12:09.240 And the way that it works is that if you 0:12:09.320 --> 0:12:12.880 were to encode every single experience that you have in 0:12:12.960 --> 0:12:16.480 a very high resolution and high fidelity kind of approach, 0:12:17.520 --> 0:12:21.760 then it becomes very difficult to generalize that to new situations. 0:12:22.080 --> 0:12:26.280 The representations in the brain become almost hyper specific. They're 0:12:26.400 --> 0:12:29.280 very very specific to those instances in which they were encoded. 0:12:29.760 --> 0:12:33.199 So being able to extract the generalities or the knowledge 0:12:33.200 --> 0:12:36.440 that you can apply to new things requires that there's 0:12:36.600 --> 0:12:40.680 enough blur, enough fuzziness across the different instances so you 0:12:40.679 --> 0:12:43.120 can generalize that knowledge. I'll give you an example. If 0:12:43.120 --> 0:12:44.520 I were to ask you what is the capital of 0:12:44.520 --> 0:12:46.960 the United States, you'd have a very very quick answer 0:12:46.960 --> 0:12:49.960 for me, which is Washington, d Z Exactly. Now, if 0:12:50.000 --> 0:12:52.120 I ask you, when did you first learn that? 0:12:54.679 --> 0:12:55.520 Now don't know. 0:12:56.440 --> 0:12:58.800 So now if I had asked you the day right 0:12:58.840 --> 0:13:01.040 after you first learned that, be in class or maybe 0:13:01.040 --> 0:13:03.200 from parents, you would have a pretty good memory for it. 0:13:03.240 --> 0:13:05.520 That's a pretty exciting thing that you just learned. But 0:13:05.679 --> 0:13:08.720 the reality is you've learned it so many times over 0:13:08.800 --> 0:13:11.400 so many different exposures. You've heard in a million times 0:13:11.559 --> 0:13:14.680 in many different settings. And what's most important is not 0:13:14.720 --> 0:13:16.240 so much the first time you heard it or the 0:13:16.320 --> 0:13:19.080 last time you heard it, but the fact that you 0:13:19.200 --> 0:13:22.000 extracted that piece of knowledge, that core piece of knowledge 0:13:22.000 --> 0:13:24.559 out and now that's part of your body of knowledge. 0:13:25.080 --> 0:13:28.240 So the specifics around how and when and where we 0:13:28.400 --> 0:13:32.160 encoded specific things may not be all that important from 0:13:32.200 --> 0:13:36.200 an evolutionary standpoint to hold on to as the memory 0:13:36.240 --> 0:13:39.920 for the actual knowledge is important. That's what's going to 0:13:39.920 --> 0:13:43.320 guide your future action. That's what's important to generalize the 0:13:43.320 --> 0:13:46.960 new situations. So in some ways there's no evolutionary pressure 0:13:47.240 --> 0:13:50.320 to hold on to the specifics over time. But it 0:13:50.360 --> 0:13:53.000 is an interesting point like why can't we have both? Well, 0:13:53.240 --> 0:13:55.320 you can think about it from an energetic standpoint. If 0:13:55.320 --> 0:13:58.520 you have a limited resource system, why would you invest 0:13:58.559 --> 0:14:01.520 your energy into storing the specifics when you know you're 0:14:01.559 --> 0:14:02.680 not going to use them down the line. 0:14:02.800 --> 0:14:06.440 Yeah, no, fair enough. So you mentioned the analogy of 0:14:06.480 --> 0:14:10.040 the brain as a computer. Is there any analogy over 0:14:10.240 --> 0:14:12.800 history comparing a brain to something else that you think 0:14:13.040 --> 0:14:15.040 is a helpful analogy or the brain is just so 0:14:15.120 --> 0:14:17.040 different it doesn't make sense to try to compare it 0:14:17.080 --> 0:14:18.880 to anything we have experience with. 0:14:19.360 --> 0:14:21.360 So that is a really interesting question. And I have 0:14:21.520 --> 0:14:24.040 thought about this before, and I keep coming back to 0:14:24.080 --> 0:14:27.800 the computer as the closest thing, and I always tell 0:14:27.840 --> 0:14:30.280 people I think it is possible that we will get 0:14:30.280 --> 0:14:32.880 to a point, perhaps with quantum computing and other types 0:14:32.920 --> 0:14:35.640 of things, where we might be able to approximate a 0:14:36.040 --> 0:14:40.240 human brain like functionality in a computer. To this day, 0:14:40.280 --> 0:14:44.000 we don't have that, even with the incredible advent of 0:14:44.040 --> 0:14:46.120 AI in large language models and all of those things. 0:14:46.160 --> 0:14:49.240 Still there are certain things that human brains can do, 0:14:49.280 --> 0:14:52.480 and mammalian brains in general can do that computers just 0:14:52.560 --> 0:14:55.760 are not capable of. But there is not another device 0:14:55.840 --> 0:14:58.920 out there that is capable of this level of processing 0:14:59.520 --> 0:15:03.160 that I can think think of to associate with that analogy. Particularly. 0:15:03.240 --> 0:15:04.880 I mean, I think one of the things that the 0:15:04.920 --> 0:15:07.960 brain does, don't get me wrong, like the computational kinds 0:15:08.000 --> 0:15:11.160 of things that have been built are incredible, and the 0:15:11.240 --> 0:15:13.240 amount of the minuscule amount of time that it takes 0:15:13.280 --> 0:15:15.120 for them to be able to process and provide an 0:15:15.120 --> 0:15:20.160 answer is just wild beyond the imagination. But there are 0:15:20.200 --> 0:15:23.480 still some things that brains can do that the computer scans, 0:15:24.120 --> 0:15:27.520 and in particular it has to do with the ability 0:15:27.560 --> 0:15:31.280 to extract knowledge, the ability to error correct, the ability 0:15:31.320 --> 0:15:34.000 to do the kinds of decision making that we do 0:15:34.400 --> 0:15:37.080 as humans that are very difficult to encapsuling in the computer. 0:15:37.240 --> 0:15:40.200 The ability to have emotion emotional reactions. Those things are 0:15:40.240 --> 0:15:42.560 still very difficult to model. While you can tell the 0:15:42.600 --> 0:15:44.400 computer all you want about what we think the human 0:15:44.440 --> 0:15:47.280 experience is, we still don't understand that well enough to 0:15:47.320 --> 0:15:48.640 be able to model it computer. 0:15:49.000 --> 0:15:51.160 Yeah, fair enough, all right, So let's pull back to 0:15:51.240 --> 0:15:54.120 memory a little bit. So we've talked about how memory 0:15:54.240 --> 0:15:58.320 differs from sentience. Are there different kinds of memory and 0:15:58.440 --> 0:16:00.800 do our brains store different kinds of manator differently? 0:16:01.480 --> 0:16:04.480 Yes, And oftentimes we just say memory as like one 0:16:04.560 --> 0:16:08.920 big blanket umbrella kind of term, But it is important 0:16:08.960 --> 0:16:11.480 to know that there are different memory types, different memory 0:16:11.480 --> 0:16:14.040 systems in the brain, and they serve different functions. So 0:16:14.120 --> 0:16:16.240 let me give you a couple of examples. One type 0:16:16.240 --> 0:16:18.440 of memory, which I tend to like quite a bit, 0:16:18.480 --> 0:16:21.400 we studied quite often in my research laboratory, is what 0:16:21.440 --> 0:16:24.840 we call episodic memory, memory for episodes, memory for events 0:16:24.840 --> 0:16:27.320 that happened to us, And we tend to kind of 0:16:27.320 --> 0:16:30.680 operationally define it as remembering what happened, where it happened, 0:16:30.680 --> 0:16:32.760 and when it happens, and whenever you have kind of 0:16:32.800 --> 0:16:35.080 like the collection or the conjunction of those three, you 0:16:35.120 --> 0:16:36.800 can label that as an episode and you have a 0:16:36.840 --> 0:16:39.840 memory for a particular episode in your life. Typically you 0:16:39.880 --> 0:16:42.880 think about that as also the root of our autobiographical memory, 0:16:42.920 --> 0:16:46.440 our memory for autobiographical experiences, things that happen to us. 0:16:47.120 --> 0:16:49.040 But that's very different from membering how to tie your 0:16:49.080 --> 0:16:52.920 shoe races, or how to ride a bicycle, or how 0:16:52.920 --> 0:16:56.520 to do something like your tennis swing or your golf swing. 0:16:57.040 --> 0:17:00.320 You know, those kinds of things are trained in the 0:17:00.320 --> 0:17:03.680 brain very differently. They involve very different systems. A lot 0:17:03.760 --> 0:17:06.520 of times, they require more trial and error kind of learning, 0:17:07.040 --> 0:17:10.320 and they tend to be a bit less accessible to consciousness. 0:17:10.760 --> 0:17:13.399 So there will call sort of implicit kinds of learning 0:17:14.400 --> 0:17:16.640 so if you look at how the brain is organized, 0:17:16.920 --> 0:17:20.040 pretty much every patch of cortex is capable of some 0:17:20.240 --> 0:17:23.040 form of memory. Another term that we typically use in 0:17:23.040 --> 0:17:26.520 neuroscience is plasticity. The idea that the brain is plastic 0:17:26.600 --> 0:17:30.200 means it's capable of change. So whenever you have experience, 0:17:30.560 --> 0:17:33.560 cells that are responding to that experience are capable of change, 0:17:33.880 --> 0:17:36.679 and that change typically is thought of as a change 0:17:36.680 --> 0:17:39.199 in the connections and the way that cells communicate with 0:17:39.240 --> 0:17:42.840 each other, but some change that reflects a record of 0:17:42.840 --> 0:17:46.000 the experience that you had. Now, those changes happen throughout 0:17:46.040 --> 0:17:48.719 They can happen in our visual cortex, our visual system, 0:17:48.920 --> 0:17:52.119 our auditory system. They can happen in the episodic memory 0:17:52.119 --> 0:17:54.160 systems in the brain, or they can happen in these 0:17:54.200 --> 0:17:57.159 more implicit memory kinds of systems in the brain that 0:17:57.240 --> 0:18:01.040 typically support more unconscious function like knowing how to ride 0:18:01.040 --> 0:18:03.480 a bicycle, like knowing how to swing the golf club 0:18:03.600 --> 0:18:06.520 and those kinds of things. Those are stored separately. And 0:18:06.560 --> 0:18:09.000 we know this to be true because we see patients 0:18:09.000 --> 0:18:11.760 that have deficits in one type of memory and not another, 0:18:11.800 --> 0:18:14.359 because they have maybe a focal stroke or some damage 0:18:14.440 --> 0:18:16.960 or some deficit that impacted one system and not the other. 0:18:17.200 --> 0:18:19.360 So they struggle with that one type of memory that's 0:18:19.359 --> 0:18:22.160 affected in that system, but everything else seems to be intact. 0:18:22.640 --> 0:18:24.880 And by type of memory does that mean like category 0:18:24.920 --> 0:18:27.880 of memories like the tennis swing and the other sort 0:18:27.880 --> 0:18:30.760 of muscle memory things, or like I could forget high 0:18:30.760 --> 0:18:33.040 school if I had a stroke in the right place right. 0:18:33.000 --> 0:18:36.760 Although that's actually increasingly difficult. So typically, if there is 0:18:36.800 --> 0:18:40.000 a stroke that is focal, it might affect motor memory. 0:18:40.040 --> 0:18:42.680 It might affect memory that allows you to kind of 0:18:42.920 --> 0:18:44.360 move your hands in the right way and be able 0:18:44.400 --> 0:18:47.240 to support that kind of function. But episodic memory is 0:18:47.280 --> 0:18:50.959 this really weird thing. Initially, it does depend on key 0:18:51.040 --> 0:18:53.080 regions of the brain, one of them being the hippocampus. 0:18:53.840 --> 0:18:56.920 That's a really important region for episodic memory. But over 0:18:57.080 --> 0:19:00.440 time memories start to become somewhat independent of the hippi 0:19:00.440 --> 0:19:03.440 campus they start to become stored elsewhere, and that's one 0:19:03.440 --> 0:19:06.560 of the reasons why in Alzheimer's disease, where we know 0:19:06.640 --> 0:19:09.840 the hippocampus is one of the earliest regions to degenerate. 0:19:10.560 --> 0:19:14.119 As that starts to go away, you see a loss 0:19:14.200 --> 0:19:18.679 of recent memories things that were recently acquired, maybe weeks, months, 0:19:18.720 --> 0:19:22.199 or a couple of years before the decline started. But 0:19:22.359 --> 0:19:26.080 things from long ago, like high school are preserved. And 0:19:26.160 --> 0:19:29.399 the reason they're preserved is that they've now been consolidated 0:19:29.440 --> 0:19:32.359 that sort of a technical term for made strength and 0:19:32.920 --> 0:19:36.160 made resilience to loss. And that's because their stored sort 0:19:36.200 --> 0:19:39.240 of in parallel throughout the brain. So just the focal 0:19:39.280 --> 0:19:42.120 deficit there is likely not going to wipe out those 0:19:42.160 --> 0:19:45.800 particular memories, but it's much more likely to wipe out say, yeah, 0:19:45.840 --> 0:19:49.119 your ability to have the right swing or ride a 0:19:49.119 --> 0:19:51.240 bicycle or anything like that. Those are the kinds of 0:19:51.240 --> 0:19:53.040 things that are much more focally stored. 0:19:53.240 --> 0:19:55.360 Okay, and can we dig a little bit more into 0:19:56.000 --> 0:19:59.160 exactly how the brain stores memories. Is it like how 0:19:59.200 --> 0:20:01.720 do neurons connect with each other? Yeah, let's dig in. 0:20:02.000 --> 0:20:06.159 Yeah. So brain cells are very very unique compared to 0:20:06.240 --> 0:20:09.440 other cells in the body. And provided this is again 0:20:09.560 --> 0:20:11.640 I always tell my students, you know, this is true 0:20:11.720 --> 0:20:14.400 ninety five percent of the time according to our knowledge today. 0:20:14.800 --> 0:20:18.200 I sometimes things you know, several weeks from now, months, years, 0:20:18.240 --> 0:20:20.280 things can get revised. So this is just according to 0:20:20.280 --> 0:20:24.080 our current knowledge today, brain cells are able to communicate 0:20:24.119 --> 0:20:26.720 with one another in a way that other cells in 0:20:26.760 --> 0:20:29.440 the body are not able to. And the way that 0:20:29.480 --> 0:20:32.479 they communicate with each other is using a combination of 0:20:32.520 --> 0:20:37.239 electricity and chemistry. So the transmission of signals within a 0:20:37.240 --> 0:20:40.920 brain cell is entirely electrical, and we can talk about 0:20:40.920 --> 0:20:43.960 that in a second, but the transmission from one cell 0:20:44.000 --> 0:20:47.040 to the next most of the time is chemical. It 0:20:47.080 --> 0:20:50.119 involves the release of a neurochemical that goes from one cell, 0:20:50.480 --> 0:20:53.880 binds to the other, and then initiates another electrical signal 0:20:54.240 --> 0:20:57.080 from the next cell to the next cell. So it 0:20:57.119 --> 0:21:01.040 goes really fast electrical, somewhat slower chemical, really fast electrical, 0:21:01.160 --> 0:21:03.760 someone slower chemical, and so on, and you have this 0:21:03.920 --> 0:21:08.040 sort of progression of communication between cells. And that's really 0:21:08.040 --> 0:21:10.760 important because these cells need to bring in signals that 0:21:11.280 --> 0:21:15.040 essentially encode the outside world and bring that knowledge into 0:21:15.080 --> 0:21:17.320 the brain to create some sort of representation of it, 0:21:17.400 --> 0:21:20.080 and then act on them. Allow us to move, allow 0:21:20.160 --> 0:21:22.720 us to avoid a threat, allow us to seek reward, 0:21:22.800 --> 0:21:24.679 all of those kinds of things. So that's how the 0:21:24.680 --> 0:21:28.200 brain typically communicates. But your question is how does memory happen? 0:21:28.920 --> 0:21:32.040 And there was sort of lots of answers over the years. 0:21:32.160 --> 0:21:34.840 We used to think, well, maybe it's encoded in the 0:21:34.920 --> 0:21:39.119 DNA and cells. Maybe it's encoded in the cell size, 0:21:39.160 --> 0:21:41.840 maybe it's encoded in the whatever else is happening to 0:21:41.960 --> 0:21:46.000 change cell shape. And the current answer is that it 0:21:46.119 --> 0:21:48.760 is much more likely to be encoded in the connections 0:21:49.560 --> 0:21:51.879 in the way that these cells communicate with one another. 0:21:51.960 --> 0:21:55.040 So let's say sell A is firing and cell B 0:21:55.280 --> 0:21:58.960 is receiving a signal from cell A. If I were 0:21:59.040 --> 0:22:02.760 to modify some how the frequency by which sell A communicates, 0:22:02.760 --> 0:22:06.640 would sell be by making it fire more, or increase 0:22:06.720 --> 0:22:11.040 the neurotransmitter release, or increase the number of receptors on 0:22:11.119 --> 0:22:14.440 the second cell that receives that neurotransmitter. I can make 0:22:14.480 --> 0:22:17.760 it so that the communication between those cells is enhanced. 0:22:18.119 --> 0:22:20.320 And the way that the analogy that I like to 0:22:20.400 --> 0:22:23.639 use for this is imagine you are at a club 0:22:24.320 --> 0:22:26.640 and there's lots and lots of noise going on, lots 0:22:26.680 --> 0:22:28.600 of things going on, lots of people talking to each other, 0:22:28.600 --> 0:22:31.679 there's loud music and so on, and you're trying to 0:22:31.680 --> 0:22:35.679 communicate something to somebody who's dancing alongside you, and it's very, 0:22:35.760 --> 0:22:38.720 very difficult because of all of that noise. But now 0:22:38.760 --> 0:22:40.280 you get real close to them and you kind of, 0:22:40.280 --> 0:22:42.159 you know, hold your hand to their ears and you 0:22:42.240 --> 0:22:45.160 start to talk directly into their ears. Now they're going 0:22:45.200 --> 0:22:47.960 to receive that communication with much higher fidelity, be able 0:22:47.960 --> 0:22:51.119 to tune out noise and selectively attend to that communication. 0:22:51.440 --> 0:22:54.520 You've enhanced the communication between that person and the person 0:22:54.520 --> 0:22:58.560 they're talking to. That's what happens at synapses. There's lots 0:22:58.560 --> 0:23:01.600 and lots of synaptic firing and lots of communication happening. 0:23:01.960 --> 0:23:04.240 But when cells start to attach to each other, they 0:23:04.280 --> 0:23:08.800 communicate much more preferentially. They can transmit signals that express 0:23:08.880 --> 0:23:11.800 that form of learning. In other words, if there's an 0:23:11.800 --> 0:23:15.280 experience that happens that is learned by the brain, the 0:23:15.320 --> 0:23:18.520 brain can express a form of plasticity or a form 0:23:18.560 --> 0:23:22.320 of memory in the strength of the connections. So if 0:23:22.359 --> 0:23:25.240 the connections grow stronger, that's a signal that this memory 0:23:25.280 --> 0:23:28.080 has been learned. And most of the information that we 0:23:28.119 --> 0:23:31.560 have about this comes from animal models, comes from slice recordings, 0:23:31.600 --> 0:23:35.400 where we can see evidence for enhancements in the connectivity, 0:23:35.760 --> 0:23:39.280 enhancement in the communication between cells as a result of 0:23:39.320 --> 0:23:40.399 a learning experience. 0:23:40.720 --> 0:23:43.920 One. You've reminded me why I hate clubs. That's sorry, 0:23:43.920 --> 0:23:45.119 no one invites me to them anymore. 0:23:45.200 --> 0:23:45.920 I share that what you do? 0:23:46.680 --> 0:23:49.720 Yeah yeah, Okay. So we've got these connections, they get strengthened, 0:23:49.760 --> 0:23:52.440 but then it feels like there's another step between having 0:23:52.440 --> 0:23:54.919 this connection and then having a like specific memory. So 0:23:54.960 --> 0:23:56.280 you know, like we're not at the point where we 0:23:56.320 --> 0:23:58.880 could even in mice and correct me if I'm wrong 0:23:58.880 --> 0:24:01.199 about this, where we could like see which neurons are 0:24:01.240 --> 0:24:05.120 firing together and know they're thinking about food. Yeah, yeah, 0:24:05.119 --> 0:24:06.160 So where do we go from there? 0:24:06.280 --> 0:24:09.000 So what you're talking about actually is a very very 0:24:09.040 --> 0:24:12.479 big problem that we deal with in neuroscience and in 0:24:12.560 --> 0:24:17.040 cognitive science, and it's the credit assignment problem. How do 0:24:17.119 --> 0:24:19.919 you know that a particular cell is assigned to a 0:24:19.920 --> 0:24:22.600 particular memory or a particular connection it's assigned to a 0:24:22.640 --> 0:24:25.359 particular memory. And it's a very challenging question and we 0:24:25.400 --> 0:24:28.040 don't know the answer yet, but we suspect There's been 0:24:28.240 --> 0:24:31.639 a lot of research on what's called mechanisms of allocation. 0:24:32.400 --> 0:24:36.080 In other words, how can you allocate particular synapses, brain 0:24:36.200 --> 0:24:40.560 cell connections and cells to a particular memory and not 0:24:40.640 --> 0:24:43.719 another right so how can we get the specificity that 0:24:43.800 --> 0:24:46.400 we need in the system. And there's been a flurry 0:24:46.440 --> 0:24:49.840 of work in recent years understanding there are certain proteins 0:24:49.840 --> 0:24:54.480 that are used to quote label synapses, label particular cells, 0:24:54.960 --> 0:24:57.520 and assign them to a one memory and not another. 0:24:58.119 --> 0:25:00.520 It's just really brilliant work by some colleagues in the 0:25:00.520 --> 0:25:03.520 field that is trying to really get at this specificity question. 0:25:03.560 --> 0:25:06.760 Now we're still early days. We don't have final answers yet, 0:25:06.920 --> 0:25:10.119 but I think we have some tentitive ideas that you 0:25:10.240 --> 0:25:13.240 can with specific proteins that are expressed in the synaps 0:25:13.520 --> 0:25:16.320 essentially label them or prime them to be the ones 0:25:16.359 --> 0:25:18.840 that are modified by this experience and maybe not another. 0:25:19.119 --> 0:25:20.880 Wow, and that's pretty cool, right. 0:25:20.840 --> 0:25:22.880 Yeah, because from the looment of the time, we thought, well, 0:25:22.880 --> 0:25:25.160 how can we ever have any specificity in our brains 0:25:25.280 --> 0:25:27.640 if memory just activates cells, how do you know which 0:25:27.640 --> 0:25:29.880 cells are the ones that are involved here? And this 0:25:29.960 --> 0:25:31.640 might actually re find us with some answers. 0:25:31.720 --> 0:25:34.720 Wow. I feel like I recently heard about the connectome project, 0:25:34.720 --> 0:25:36.720 which I think is trying to figure out all of 0:25:36.760 --> 0:25:39.239 the neurons. So does this suggest that once we have 0:25:39.280 --> 0:25:42.400 a connectome next we need to work on the proteome 0:25:42.520 --> 0:25:45.080 that connects to the connectome to really understand how all 0:25:45.119 --> 0:25:47.720 of this works, or how helpful is this connect dome 0:25:47.720 --> 0:25:48.400 project going to. 0:25:48.320 --> 0:25:51.160 Be very helpful? I think that every time we try 0:25:51.200 --> 0:25:54.040 it and map another home it is very helpful. At 0:25:54.080 --> 0:25:56.959 some point we all have an everything owned and you know, 0:25:57.040 --> 0:25:59.919 with that sort of large scale data effort, we're going 0:25:59.920 --> 0:26:02.760 to need also the AI, the machine learning, all of 0:26:02.800 --> 0:26:05.200 those tools people to pass through it and actually figure 0:26:05.240 --> 0:26:07.800 out what's going on. But it's interesting, you know, Kelly, 0:26:08.000 --> 0:26:10.080 When I was coming up as a student, there was 0:26:10.119 --> 0:26:13.280 always this question that was asked by faculty in my 0:26:13.400 --> 0:26:16.720 department and many other departments, And it's a theoretical question, 0:26:16.840 --> 0:26:19.480 and I want to pose that question to you, which is, 0:26:19.680 --> 0:26:22.679 if we were to map every single neuron in the 0:26:22.680 --> 0:26:26.520 brain and every single connection in the brain, would we 0:26:26.560 --> 0:26:30.199 have learned anything about how the brain actually functions? And 0:26:30.320 --> 0:26:33.199 whenever they asked that question, you know, some of us 0:26:33.200 --> 0:26:34.919 were attempted to say, well, yeah, of course you can 0:26:35.040 --> 0:26:37.080 have all the data, right, And the answer they wanted 0:26:37.160 --> 0:26:38.960 us to get to is no, you're no better off 0:26:39.000 --> 0:26:41.440 because you have a ton of data but no way 0:26:41.520 --> 0:26:45.240 to really test hypotheses and understand function. You have to 0:26:45.280 --> 0:26:47.040 have the right model, You have to have the right 0:26:47.119 --> 0:26:50.000 kind of strategy to go into that data and look 0:26:50.040 --> 0:26:53.280 for what's necessary. But I would argue that over the 0:26:53.359 --> 0:26:57.200 last twenty thirty years that thinking has evolved and now 0:26:57.760 --> 0:27:01.200 we can go in in a completely unsupervised without having 0:27:01.240 --> 0:27:03.800 a model, which means also we avoid some of the 0:27:03.840 --> 0:27:06.840 biases that might come from a model and ask what 0:27:06.880 --> 0:27:09.520 does the data tell us? Sure, there is an explosion 0:27:09.520 --> 0:27:12.040 of data, but there are patterns that are hidden in there, 0:27:12.280 --> 0:27:14.640 and if you train up AI enough, it can pick 0:27:14.680 --> 0:27:17.480 up on those patterns and maybe tell us that there's 0:27:17.520 --> 0:27:19.720 a new model. There's a different model. The way that 0:27:19.720 --> 0:27:22.520 we were thinking about the brain informing hypotheses may not 0:27:22.560 --> 0:27:25.119 have been right all along. So I go back to 0:27:25.200 --> 0:27:28.120 things like the connect home projects and trying to resolve 0:27:28.160 --> 0:27:31.880 the connect home, the proteome, the epigenome, all of those 0:27:32.000 --> 0:27:36.000 kinds of things as different layers of knowledge about the 0:27:36.000 --> 0:27:38.960 nervous system. And if we have all of that information, 0:27:39.000 --> 0:27:41.399 it stands to reason that we should be able to 0:27:41.440 --> 0:27:45.119 pick up on patterns, and patterns can maybe transform the 0:27:45.160 --> 0:27:47.720 way that we think about the brain. Maybe we're all 0:27:47.720 --> 0:27:51.800 along maybe the brain does quantum computing. Maybe all sorts 0:27:51.840 --> 0:27:54.560 of things that we just would have never imagined that 0:27:54.600 --> 0:27:56.040 are buried in that data. 0:27:56.119 --> 0:27:57.919 It sounds like an exciting time to be in the field. 0:27:58.119 --> 0:27:59.719 Oh. Absolutely, absolutely. 0:28:16.080 --> 0:28:17.280 I'm going to pull us back a little bit. In 0:28:17.320 --> 0:28:19.720 our conversation. You were talking about how you can strengthen 0:28:19.760 --> 0:28:23.600 connections between neurons. Does that happen because you're thinking of 0:28:23.640 --> 0:28:25.960 the same memory over and over again? And so how 0:28:25.960 --> 0:28:27.919 do memories get strengthened and how do we lose some 0:28:28.000 --> 0:28:28.439 of them? 0:28:28.520 --> 0:28:32.280 Yeah, So the strengthening of memory, or the idea of consolidation, 0:28:32.400 --> 0:28:34.680 which is exactly what it sounds like. It's making memories 0:28:34.720 --> 0:28:38.320 more solidified or more strengthened. It can happen because we 0:28:38.440 --> 0:28:41.840 are repeatedly rehearsing the memory, so we're thinking about it 0:28:41.880 --> 0:28:44.240 over and over. But the good news, Kelly, is that 0:28:44.240 --> 0:28:48.400 that happens completely incidentally, without you intentionally trying to do it. 0:28:48.640 --> 0:28:51.400 Your brain constantly brings up old memories and thinks about them, 0:28:51.480 --> 0:28:53.520 and even if you're not consciously aware of it, it happens 0:28:53.560 --> 0:28:56.440 while you sleep at night. Okay, so the brain is 0:28:56.440 --> 0:28:59.760 sort of on the back burner, constantly playing through these memories, 0:29:00.080 --> 0:29:02.320 replaying through these memories, and even when you go to sleep, 0:29:02.480 --> 0:29:05.000 it's replaying through these memories. So the strengthening act of 0:29:05.080 --> 0:29:08.880 memories doesn't have to be this intentional thing, which I 0:29:08.920 --> 0:29:11.080 think is a really powerful thing to tell students. Also, 0:29:11.240 --> 0:29:12.960 you don't have to sit here and like regurgitate and 0:29:13.040 --> 0:29:15.480 rehearse everything over and over and over. Just go through 0:29:15.520 --> 0:29:18.560 and understand and then get a good night's sleep, right, 0:29:18.720 --> 0:29:20.520 which is a lot of them really struggle to do. 0:29:20.840 --> 0:29:24.080 But during that period you might think, well, that's just rest. 0:29:24.400 --> 0:29:26.960 Actually the brain can be quite active during that period 0:29:27.000 --> 0:29:29.080 of time and can be playing through these memories and 0:29:29.120 --> 0:29:32.760 storing them and trying to make them morsistant to forgetting now. 0:29:33.160 --> 0:29:37.000 One thing to note also is that when you replay memories, 0:29:37.040 --> 0:29:40.560 when you bring back memories, you don't end up with 0:29:40.680 --> 0:29:44.720 the same thing being stored again. So memories are reconstructive 0:29:44.720 --> 0:29:47.000 in nature. If I were to bring back an experience, 0:29:47.000 --> 0:29:48.920 say that I have from a few weeks ago and 0:29:49.040 --> 0:29:51.680 talk about it with you, what I end up storing 0:29:51.760 --> 0:29:55.640 now and reinforcing is a somewhat altered version of that memory. 0:29:55.880 --> 0:29:58.800 It's not the same thing, because memory is reconstructed on 0:29:58.880 --> 0:30:01.880 piecing together the pieces. Other pieces just get incorporated because 0:30:01.880 --> 0:30:04.239 we're having a conversation about it. And then later on 0:30:04.280 --> 0:30:07.160 what I remember is some amalgamation of all of those 0:30:07.200 --> 0:30:09.640 experiences when I brought it back and changed it ever 0:30:09.760 --> 0:30:12.600 so slightly. My colleague here at you see, Aravin Beth 0:30:12.640 --> 0:30:16.000 Loftus built her career on studying false memories and how 0:30:16.080 --> 0:30:19.280 they arise, and they are very, very frequent. They arise 0:30:19.360 --> 0:30:21.960 all the time. We generate the more as we get older, 0:30:22.160 --> 0:30:24.640 and they happen just by virtue of our memory being 0:30:24.960 --> 0:30:29.920 a reconstructive system rather than a high fidelity video camera 0:30:30.240 --> 0:30:33.520 or a picture of reality. It's just a sort of 0:30:33.520 --> 0:30:36.200 a Hodgepodg construction of what that reality might have been. 0:30:36.360 --> 0:30:39.520 And again we say, why is this happening? Why can't 0:30:39.560 --> 0:30:42.120 we have a high fidelity version of things? And it's 0:30:42.160 --> 0:30:44.960 possible that we just don't need to. So even with 0:30:45.040 --> 0:30:48.400 these false memories arising, they're very artifactual, like you really 0:30:48.400 --> 0:30:50.760 need to remember exactly what happened and where it happened, 0:30:50.800 --> 0:30:52.560 that when it happened, Ergie, you just need to remember 0:30:52.600 --> 0:30:55.440 the core knowledge. So if we focus on, hey, the 0:30:55.480 --> 0:30:59.040 corenology is being remembered accurately. That's all that matters. Everything 0:30:59.080 --> 0:31:01.840 else and go to crap, and nobody's going to be 0:31:01.920 --> 0:31:04.560 less able to survive. So from a survival standpoint, it 0:31:04.600 --> 0:31:07.720 certainly doesn't matter that you have this strengthening, be a 0:31:07.800 --> 0:31:10.440 very high fidelity strengthening. It just matters that the core 0:31:10.480 --> 0:31:13.480 component knowledge is the thing that strengthened, Like the capital 0:31:13.520 --> 0:31:16.480 of the United States, Washington, everything else. Who cares. 0:31:16.880 --> 0:31:19.880 But if the lawyer is you priding you for details 0:31:19.880 --> 0:31:22.640 in a court case, that's when you're in some trouble. 0:31:22.880 --> 0:31:26.000 Absolutely, and you know the good news is, well, the 0:31:26.160 --> 0:31:29.640 somewhare good news is some lawyers, some federal judges, some 0:31:29.800 --> 0:31:35.040 jury get the lecture about false memories and understand that 0:31:35.120 --> 0:31:37.000 when you call witnesses to to stand and you're asking 0:31:37.080 --> 0:31:40.160 very very specific questions, that their right collection is going 0:31:40.200 --> 0:31:42.880 to be some combination of what actually happens, what the 0:31:42.960 --> 0:31:45.600 brain sort of reconstructed it to be, what kinds of 0:31:45.680 --> 0:31:49.680 questions are being asked, the pressure, any interrogation that happened earlier, 0:31:49.760 --> 0:31:52.800 All of those things sort of weave their way into 0:31:52.840 --> 0:31:54.800 that memory. You're never going to be able to get 0:31:54.800 --> 0:31:58.719 this beautiful, accurate, one hundred percent depiction of what happens, 0:31:58.760 --> 0:32:01.400 you're going to get some very of it that could 0:32:01.400 --> 0:32:03.000 be quite a bit more corrupted. 0:32:03.240 --> 0:32:05.120 Gosh, there could be a whole podcast on that topic. 0:32:05.760 --> 0:32:09.960 So my co host wanted me to dig into how 0:32:10.000 --> 0:32:12.040 we learn about this kind of stuff. So you mentioned 0:32:12.040 --> 0:32:15.200 that there are animal models, but just focusing on people 0:32:15.280 --> 0:32:19.840 right now, how good are our techniques for watching how 0:32:19.880 --> 0:32:22.240 the brain works in living humans to sort of try 0:32:22.280 --> 0:32:23.560 to get a handle on some of this stuff. 0:32:23.760 --> 0:32:27.840 Yeah, So when we started out, the discipline of neuropsychology 0:32:28.000 --> 0:32:31.280 had very, very poor tools available to it. So you 0:32:31.400 --> 0:32:34.400 have to develop cognitive assessments, which have come a long way. 0:32:34.480 --> 0:32:36.480 You can have the right kinds of cognitive assessments and 0:32:36.520 --> 0:32:38.720 so on, but you really have to work with patients 0:32:38.720 --> 0:32:42.120 and the clinic who come in presenting with memory problems, 0:32:42.200 --> 0:32:45.480 with a variety of different conditions, and essentially it's akin 0:32:45.560 --> 0:32:49.239 to leision studies. You're working with patients who might have 0:32:49.640 --> 0:32:52.000 circumscribed focal deficit in the brain. You can see that 0:32:52.040 --> 0:32:54.760 on structural MRI for example, and say this part of 0:32:54.760 --> 0:32:57.400 the brain is damaged or missing. Therefore they have this 0:32:57.560 --> 0:32:59.760 kind of function, So you might be able to say 0:32:59.800 --> 0:33:01.760 something about the function of this part of the brain 0:33:01.800 --> 0:33:06.400 in a healthy person. But our tools have evolved significantly since, 0:33:06.600 --> 0:33:09.640 so two major advances that I can tell you are 0:33:09.680 --> 0:33:12.520 still today. The chief ways by which we study this. 0:33:12.960 --> 0:33:14.880 One is functional MRI, and we tend to do a 0:33:14.960 --> 0:33:16.680 heck of a lot of that in my lab. So 0:33:16.840 --> 0:33:19.560 functional MRI operates on the principle that you can put 0:33:19.600 --> 0:33:22.960 somebody in the scanner totally intact brain and give them 0:33:23.040 --> 0:33:25.840 a game to play, or a memory task, or any 0:33:25.840 --> 0:33:28.920 sort of challenge that would engage the memory bits of 0:33:29.000 --> 0:33:32.200 their brain, for example. And what you're imaging with functional 0:33:32.280 --> 0:33:35.920 MRI is not neural activity directly. What you're imaging is 0:33:35.960 --> 0:33:39.840 blood flow. The idea being that if there's a patch 0:33:39.920 --> 0:33:44.160 of cortex patchup brain that is more active, that is 0:33:44.280 --> 0:33:47.840 engaged in this challenge, it's going to require oxygen and 0:33:47.880 --> 0:33:51.360 glucose and it's going to try to extract that out 0:33:51.360 --> 0:33:55.880 of the blood flow. So by mapping how much oxygenated 0:33:55.960 --> 0:33:59.760 blood and deoxygenated blood are going to different areas in 0:33:59.800 --> 0:34:03.040 the brain, you can generate a contrast because it turns 0:34:03.040 --> 0:34:06.080 out that the degree of oxygenation has a different magnetic signal. 0:34:06.320 --> 0:34:07.880 So that's sort of a little hack that we pull 0:34:07.920 --> 0:34:11.600 in MRI because we're changing ragnetic fields. So by measuring 0:34:11.640 --> 0:34:15.640 that contrast, we can get an indirect proxy to where 0:34:15.719 --> 0:34:19.440 neural activity might be by virtue of that blood flow change. 0:34:19.880 --> 0:34:22.400 So that's been a really, really helpful technique since the 0:34:22.560 --> 0:34:25.480 late nineties early two thousands. In the early days of 0:34:25.480 --> 0:34:28.319 functional MRI, people did a bunch of like really just 0:34:28.440 --> 0:34:31.560 awful studies because the technology was new and we didn't 0:34:31.560 --> 0:34:33.800 know what to do with it, and folks didn't really 0:34:34.320 --> 0:34:36.839 think beyond you know, the X marks the spot kind 0:34:36.840 --> 0:34:39.680 of approach, Right, I want to know what the fill 0:34:39.719 --> 0:34:42.080 in the blank part of the brain is. It even 0:34:42.120 --> 0:34:43.799 got as absurd as I want to know what the 0:34:43.840 --> 0:34:46.200 god part of the brain is. Right, So people start 0:34:46.239 --> 0:34:48.080 to do those kinds of studies, try to go in 0:34:48.160 --> 0:34:50.800 and say, X marks the spot, where's the stuff happening? 0:34:51.160 --> 0:34:54.919 Is this the same system where they had that dead trout? Oh? 0:34:55.000 --> 0:34:58.080 Yeah, you know that that trout study. Of course. So 0:34:58.239 --> 0:34:59.960 at the end of the day, it is a statistic 0:35:00.160 --> 0:35:04.840 approach to comparing activation, and yeah, that study is really 0:35:04.840 --> 0:35:07.480 compelling because you could show that you see activation essentially 0:35:07.520 --> 0:35:10.920 in something that is dead, and people every now and 0:35:10.960 --> 0:35:12.600 then will kind of make fun of this, and remember 0:35:12.680 --> 0:35:15.080 the old days of fMRI, when folks didn't really know 0:35:15.120 --> 0:35:16.920 what they were doing, and you could get something like 0:35:16.960 --> 0:35:19.480 this right, and in some cases you can even get 0:35:19.480 --> 0:35:21.520 it to be published, which is crazy when you think 0:35:21.560 --> 0:35:25.400 about it. But we've come a long way since. So 0:35:25.480 --> 0:35:28.160 the beauty of functional MRI now is that one we 0:35:28.320 --> 0:35:30.359 understand how to do the X marks the spot much 0:35:30.440 --> 0:35:32.239 much better. We now have much better handle on this 0:35:32.440 --> 0:35:35.279 historical challenges, the way to build the right contrasts, the 0:35:35.320 --> 0:35:37.800 way to correct for multiple comparisons, all the things that 0:35:37.840 --> 0:35:40.880 you tend to think of when you're doing large scale statistics. 0:35:41.600 --> 0:35:44.360 That discipline had to kind of come to functional imaging 0:35:44.560 --> 0:35:46.920 and inform it and that has happened, which is great. 0:35:47.640 --> 0:35:49.440 But the second part is I told you before that 0:35:49.520 --> 0:35:52.719 memory is all about the connections, and functional MRI initially 0:35:53.040 --> 0:35:56.400 was all about blobbology, right, try to find little hotspots 0:35:56.400 --> 0:35:58.960 in the brain. You pretty pictures the cover of science 0:35:58.960 --> 0:36:01.960 and all that with little hotspots in the brain, and 0:36:02.040 --> 0:36:04.440 that was the approach. But we know that memory is 0:36:04.440 --> 0:36:07.239 not in the hotspots, memories and the connections, so we've 0:36:07.239 --> 0:36:11.360 started to move much more towards connectivity analysis and asking 0:36:11.400 --> 0:36:14.759 about how are the different parts of the brain communicating 0:36:14.840 --> 0:36:19.960 dynamically and essentially coactivating with each other to support solving 0:36:19.960 --> 0:36:22.799 this challenge or doing this memory test or memory game 0:36:22.880 --> 0:36:25.720 while you're in the scanner. So that was the advent 0:36:25.719 --> 0:36:29.040 of functional connectivity kinds of approaches which are I think 0:36:29.120 --> 0:36:32.319 far more compelling, far more robust against some of the 0:36:32.360 --> 0:36:36.160 initial critiques of a functional MRI, and they reflect the 0:36:36.200 --> 0:36:38.040 true nature of how the brain works. The brain is 0:36:38.080 --> 0:36:41.640 one big dynamical system. It's not just regions working in isolation. 0:36:41.960 --> 0:36:44.880 Everything is connecting with each other, so we owe it 0:36:44.920 --> 0:36:47.239 to ourselves to try to understand it from that much 0:36:47.239 --> 0:36:51.319 more complex way. So functional MRI still remains a very 0:36:51.400 --> 0:36:54.000 very powerful tool, but now the analysis that we can 0:36:54.040 --> 0:36:56.759 do are just far more advanced. The other thing that 0:36:56.880 --> 0:37:00.640 I think is just incredibly powerful, aside from anim models, 0:37:00.880 --> 0:37:05.040 is the ability to directly record electrical activity from cells 0:37:05.640 --> 0:37:08.279 or from what it's called local field potentials that the 0:37:08.360 --> 0:37:11.440 areas around cells that have also electrical activity. It can 0:37:11.480 --> 0:37:16.120 be measured directly in patients, and these are typically patients 0:37:16.160 --> 0:37:19.839 that are going to undergo surgery for epileptic seizures. So 0:37:19.920 --> 0:37:22.759 the surgery is done to remove the part of the 0:37:22.760 --> 0:37:26.160 brain where the seizures are emanating from. And typically when 0:37:26.160 --> 0:37:28.120 they come into a hospital, they're in a hospital for 0:37:28.120 --> 0:37:31.120 about a week or so. They get implanted with electrodes 0:37:31.160 --> 0:37:33.719 to record from the parts of the brain where the 0:37:33.760 --> 0:37:38.040 clinician might suspect that epilepsy is happening, and they're taken 0:37:38.120 --> 0:37:41.400 off of anti epileptic medication and essentially they're waiting to 0:37:41.480 --> 0:37:44.520 induce a seizure, and once that seizure is induced, they 0:37:44.560 --> 0:37:47.160 attract the location. That's how they decide on a way 0:37:47.200 --> 0:37:50.319 to do the surgery. There's about a week or so 0:37:50.400 --> 0:37:53.879 while they're in the hospital with electrodes penetrating deep into 0:37:53.920 --> 0:37:56.719 their cortex and many of those electrodes directly into the 0:37:56.760 --> 0:37:59.759 memory bits of the brain, like the hippocampus. And those 0:38:00.360 --> 0:38:04.640 are just an incredible group of individuals because they also 0:38:04.880 --> 0:38:07.120 most of them want to help science and they understand 0:38:07.120 --> 0:38:10.239 the opportunity the scientists have while they're laying in a 0:38:10.239 --> 0:38:13.560 hospital bed for about a week to understand something fundamental 0:38:13.600 --> 0:38:16.319 about the brain. So every now and then they give 0:38:16.400 --> 0:38:18.680 us the opportunity to give them a challenge, maybe on 0:38:18.719 --> 0:38:21.239 an iPad or a computer while they're laying there and 0:38:21.440 --> 0:38:24.080 they try to solve this challenge, try to play this 0:38:24.160 --> 0:38:27.000 memory game or do this memory test while we're recording 0:38:27.120 --> 0:38:30.839 direct electrical activity from their brain cells, which is incredible. 0:38:31.239 --> 0:38:34.560 So it gives us almost the same degree of information 0:38:34.600 --> 0:38:36.480 that you can get in an animal model. Now in 0:38:36.520 --> 0:38:38.040 an animal model, in a road that you can stick 0:38:38.080 --> 0:38:41.400 more electrones, you can get higher fidelity. And with patients 0:38:41.400 --> 0:38:43.720 you have to do things that are only clinically warranted. 0:38:43.760 --> 0:38:46.160 So there's an ethical obligation, of course to make sure 0:38:46.200 --> 0:38:48.920 that nothing is being done that would ever put the 0:38:48.960 --> 0:38:53.120 patient an increase risk. So that also poses some limitations 0:38:53.120 --> 0:38:55.920 as to how you can record activity and get that data. 0:38:56.040 --> 0:38:58.640 But it's just incredible access that we have to the 0:38:58.719 --> 0:39:02.520 brain in partnership with these remarkable individuals, and we've learned 0:39:02.520 --> 0:39:04.200 a heck of a lot about how the brain works 0:39:04.200 --> 0:39:07.120 and how memory works from those direct electrical recordings. 0:39:07.719 --> 0:39:11.040 Wow. I previously wrote a chapter on brain computer interfaces 0:39:11.080 --> 0:39:14.560 and I was reading about like, utah arrays. Is this 0:39:14.719 --> 0:39:17.000 the same thing or is this a different kind of electrode. 0:39:17.080 --> 0:39:20.239 Yes, So, utah arrays are one way to do it. 0:39:20.680 --> 0:39:24.640 Utah arrays are a little bit more invasive. They involve 0:39:24.800 --> 0:39:27.320 several electrodes that are kind of going through the surface 0:39:27.400 --> 0:39:30.040 of the cortex. At the same time, they're no longer 0:39:30.160 --> 0:39:33.160 kind of the standard practice for most patients. They're still 0:39:33.280 --> 0:39:35.960 used in some cases where they're clinically warranted, but in 0:39:36.000 --> 0:39:39.680 many cases they're not because you suspect that what's happening 0:39:39.760 --> 0:39:42.800 is deep into the brain, so you stick direct single 0:39:42.840 --> 0:39:45.600 electrodes all the way down to where you suspect the 0:39:45.680 --> 0:39:48.440 action might be, and you avoid some of the potential 0:39:48.520 --> 0:39:50.920 damage that happens with UTAH rays. So they're used in 0:39:50.960 --> 0:39:54.760 some clinical contexts, but in many others, we can stick 0:39:54.840 --> 0:39:58.719 these much thinner, slimmer electrodes directly into the parts of 0:39:58.760 --> 0:40:01.440 the brain that we suspect yet epilepsy is ennything from 0:40:01.719 --> 0:40:04.720 so far less damage that way, and those patients typically 0:40:04.719 --> 0:40:08.120 have better outcomes than patients implanted with guitar rays. Now, 0:40:08.200 --> 0:40:11.280 your point about BCIs, and there's a number of companies 0:40:11.320 --> 0:40:14.160 out there that are trying to develop brain computer interfaces 0:40:14.239 --> 0:40:16.960 using these kinds of arrays. I think that's a particular 0:40:17.040 --> 0:40:20.560 challenge for those enterprises is how do you create a 0:40:20.600 --> 0:40:23.759 way to measure directly from the brain and to be 0:40:23.800 --> 0:40:26.880 able to stimulate and influence the brain without causing too 0:40:26.960 --> 0:40:30.359 much damage. Having electrones that are thin enough, that are 0:40:30.640 --> 0:40:33.080 made from the right material so that you don't cause 0:40:33.120 --> 0:40:35.600 a lot of tissue damage, because ideally, what you want 0:40:35.600 --> 0:40:37.400 to do is create an interface that helps people, so 0:40:37.440 --> 0:40:40.200 you don't want to inadvertently cause more damage. 0:40:40.400 --> 0:40:42.960 Now, when we were thinking about UTAH rays and damage, 0:40:43.000 --> 0:40:45.359 you know, we thought about like a cup with jello 0:40:45.480 --> 0:40:48.279 in it, and you stick some needles in there, and 0:40:48.360 --> 0:40:50.400 as you move the jello around, if the needles are 0:40:50.440 --> 0:40:52.120 kind of staying in place, that would sort of mess 0:40:52.200 --> 0:40:53.600 up the brain. Is that a good way to think 0:40:53.640 --> 0:40:55.080 about it? Does it all move together? 0:40:55.520 --> 0:40:59.200 Yeah? The brain certainly is as vulnerable maybe as a 0:40:59.239 --> 0:41:02.960 cup of gello. But the key is also flexibility. So 0:41:02.960 --> 0:41:05.520 you're right. When you have these electrodes, there's a bit 0:41:05.560 --> 0:41:08.759 of a compromise. So want them to be flexible so 0:41:08.800 --> 0:41:10.719 that they're moving with their brain. You're absolutely right, and 0:41:10.760 --> 0:41:13.439 that'll cause less tissue damage. But at the same time, 0:41:13.520 --> 0:41:16.000 flexibility you can come at a cost, which is what 0:41:16.120 --> 0:41:19.200 they're targeting, might change. So you want to make them 0:41:19.200 --> 0:41:21.720 flexible enough sort of they don't cause damage, but rigid 0:41:21.800 --> 0:41:23.960 enough so that they can continue to target the same region, 0:41:24.800 --> 0:41:27.359 so it is not an easy challenge at all. But 0:41:27.560 --> 0:41:30.520 there's been some developments recently in doing these kinds of 0:41:30.600 --> 0:41:33.839 arrays with animals, and we haven't yet pourted that over 0:41:33.920 --> 0:41:36.080 to humans and done the FD approval and all of 0:41:36.080 --> 0:41:39.280 those kinds of things. It's happening soon. There's already experiments 0:41:39.280 --> 0:41:41.840 that try to test out one of the technologies like 0:41:41.920 --> 0:41:45.959 neuropixel for example, or near epixels technologies. Those have been 0:41:46.400 --> 0:41:49.799 incredibly powerful for animal models for reading from road insight 0:41:49.840 --> 0:41:53.400 from non human primates and their small form factor. They're thinner, 0:41:53.400 --> 0:41:55.720 but they have a ton of electrode contacts on there, 0:41:56.040 --> 0:41:58.200 so it can really give you information from a lot 0:41:58.239 --> 0:42:02.480 of different sounds simultaneou sleep. And pointing that over to 0:42:02.560 --> 0:42:04.840 humans I think will be a really helpful thing to do. 0:42:05.160 --> 0:42:07.360 But that's only been done in some limited experiments and 0:42:07.440 --> 0:42:10.200 not widespread. You so hoping that some variants of those 0:42:10.280 --> 0:42:12.600 kinds of technologies will make us way to primetime soon. 0:42:12.840 --> 0:42:16.160 I've watched some videos of people with brain computer interfaces 0:42:16.200 --> 0:42:18.040 that were able to do incredible things, But one of 0:42:18.080 --> 0:42:20.560 the things that sounded totally devastating to me was if 0:42:20.600 --> 0:42:23.719 I understand this correctly, it's over time, the brain has 0:42:23.719 --> 0:42:26.600 a response to those electrodes and like kind of walls 0:42:26.600 --> 0:42:28.520 them off and the connection gets less good. I don't 0:42:28.560 --> 0:42:31.120 know exactly what's happening. Do we have any progress in 0:42:31.120 --> 0:42:31.560 that area. 0:42:32.080 --> 0:42:34.360 Well, so that's another thing that needs to be tackled. Also, 0:42:34.440 --> 0:42:37.840 with some of these newer silicon probes, they're less likely 0:42:37.920 --> 0:42:41.800 to have the inflammatory and the calcification kinds of responses 0:42:41.800 --> 0:42:44.080 that happened around electrodes, because remember, this is a foreign 0:42:44.160 --> 0:42:47.840 object entering the brain, and the brain's natural disposition towards 0:42:47.880 --> 0:42:50.840 foreign objects is attack it, right. That's why we have 0:42:51.280 --> 0:42:54.319 brains immune cells, we have microglia, we have a lot 0:42:54.320 --> 0:42:58.120 of cells that are dedicated to detecting and eliminating foreign objects. 0:42:58.680 --> 0:43:02.000 So you tend to see them of aggregate around electrodic 0:43:02.000 --> 0:43:05.760 contact locations and things like that. But there are ways 0:43:05.800 --> 0:43:08.399 with different substances to kind of maybe fool the brain 0:43:08.480 --> 0:43:10.880 a little bit into thinking this is okay. You can 0:43:10.920 --> 0:43:13.040 try to also reduce the brains immune response to some 0:43:13.120 --> 0:43:16.120 extent when these things are coming in. So there's approaches 0:43:16.120 --> 0:43:18.319 that are being developed to try to get better long 0:43:18.400 --> 0:43:21.120 term outcomes, but yet we're still very early. 0:43:20.920 --> 0:43:22.799 In this game, And for listeners who are maybe not 0:43:22.880 --> 0:43:25.640 es familiar with brain computer interfaces, what are some reasons 0:43:25.680 --> 0:43:28.160 that people might get a brain computer interface. 0:43:28.320 --> 0:43:31.360 There's a variety of reasons. So, for example, for someone 0:43:31.400 --> 0:43:34.520 who has lost the ability to control their limbs because 0:43:34.560 --> 0:43:37.640 of a stroke or a focal deficit, being able to 0:43:37.680 --> 0:43:40.680 have a brain computer interface shortcut signals so that they 0:43:40.680 --> 0:43:43.960 can still control their limbs and their body is remarkable. 0:43:44.000 --> 0:43:46.840 And patients who have had those kinds of approaches, it 0:43:46.920 --> 0:43:49.840 is just life changing. They go from a paraplegic or 0:43:49.880 --> 0:43:52.160 quadriplegic to being able to have use of their arms 0:43:52.239 --> 0:43:56.240 or their legs again. So there's incredibly utility there. For 0:43:56.440 --> 0:44:00.880 folks who might have epilepsy. For example, there is a 0:44:00.920 --> 0:44:05.279 brain computer interface that is a stimulator that is implanted 0:44:05.280 --> 0:44:07.920 in the brain that responds to the earliest science of 0:44:07.920 --> 0:44:11.480 epileptic seizures and that is able to with electrical stimulation 0:44:11.600 --> 0:44:14.600 essentially knock it out. So now instead of having to 0:44:14.680 --> 0:44:17.280 have the person be going in for surgery and lomping 0:44:17.360 --> 0:44:19.440 up parts of the brain or having them be devastated 0:44:19.480 --> 0:44:23.359 by epileptic seizures, you can have an implanted BCI that 0:44:23.520 --> 0:44:26.400 responds in a closed loop system, so it uses the 0:44:26.400 --> 0:44:29.279 responses of the brain itself to tell the stimulator what 0:44:29.360 --> 0:44:32.000 to do. And that's a completely closed loop, so it 0:44:32.040 --> 0:44:35.680 doesn't require any user interventionally outside. That allows it to 0:44:35.719 --> 0:44:38.960 do a much better job of helping the patients overcome 0:44:39.600 --> 0:44:43.080 seizures or epilepsy. So there's a number of different uses. 0:44:43.160 --> 0:44:46.240 I can imagine that for movement disorders, for a variety 0:44:46.280 --> 0:44:49.200 of different conditions where you might want to implant something 0:44:49.280 --> 0:44:51.200 that communicates with the brain and feeds at the right 0:44:51.239 --> 0:44:53.600 signal at the right time, there's going to be a 0:44:53.719 --> 0:44:57.080 huge use for a BCI. Then there's a whole other 0:44:57.160 --> 0:45:02.040 class of uses that may not work vire implantation. Right, 0:45:02.120 --> 0:45:05.880 So these external devices maybe devices that are communicating with 0:45:05.920 --> 0:45:10.600 the brain and external fashion portable or multiple, and they 0:45:10.640 --> 0:45:14.960 allow it to improve function for stroke rahabilitation, or improve 0:45:15.000 --> 0:45:17.480 function in some other way. There's a lot of folks 0:45:17.520 --> 0:45:20.520 also kind of you know, taking the transhumanist approach here 0:45:20.520 --> 0:45:22.760 and trying to develop PCIs to just improve our function. 0:45:22.960 --> 0:45:25.319 We just want to be better at something, right, So 0:45:25.360 --> 0:45:27.239 what if I can control this robotic arm to do 0:45:27.320 --> 0:45:29.920 some you know, whatever it is. So don't care too 0:45:30.000 --> 0:45:33.800 much about those but certainly the utility for helping patients 0:45:33.880 --> 0:45:34.600 is huge. 0:45:34.920 --> 0:45:37.200 So getting a little more sci fi here, do you 0:45:37.239 --> 0:45:40.080 think we'll ever be able to know what somebody is 0:45:40.120 --> 0:45:42.839 thinking by having, you know, a cap on their head 0:45:42.920 --> 0:45:45.600 or electrodes in their brain or is that just way 0:45:45.640 --> 0:45:46.279 too far off? 0:45:46.520 --> 0:45:49.600 I think we already do so. I think we are 0:45:49.719 --> 0:45:53.799 to some extent with an electrocapsule. Egen is really the 0:45:53.840 --> 0:45:56.640 technology that you're talking about, or there's other ways to 0:45:56.640 --> 0:46:00.480 do it also, various ultrasound technologies and so on. You 0:46:00.520 --> 0:46:04.440 can detect and stimulate pretty easily, but the problem is 0:46:04.560 --> 0:46:06.600 the kinds of things that you can get the system 0:46:06.640 --> 0:46:09.360 to do are still fairly rudimentary. So I can tell, 0:46:09.440 --> 0:46:12.600 for example, based on eg signal whether the person is 0:46:12.640 --> 0:46:16.279 going to move their hand or make some overt kind 0:46:16.320 --> 0:46:20.040 of gesture, and motor control is a somewhat simpler system 0:46:20.080 --> 0:46:25.200 than like memory, executive decision, or emotion or having very 0:46:25.200 --> 0:46:29.120 complex feelings like guilt, right or things like that are 0:46:29.719 --> 0:46:33.160 much more difficult to capture in the simple signals that 0:46:33.160 --> 0:46:36.640 we're capturing. The BCIs right now. So do I anticipate 0:46:36.640 --> 0:46:38.960 that at one point we'll be able to do one percent? 0:46:39.120 --> 0:46:42.000 There's no doubt the technologies there. It's just a matter 0:46:42.080 --> 0:46:44.799 of are we recording from enough are we able to 0:46:44.840 --> 0:46:48.399 build the sophisticated models to model this function, and we're 0:46:48.400 --> 0:46:51.759 making rapid progress in that arena. So from a sci 0:46:51.760 --> 0:46:55.400 fi perspective, I'm sure you've heard this before. The moving vehicle, 0:46:55.480 --> 0:46:57.680 the car was sci fi at one point until someone 0:46:57.680 --> 0:47:00.600 invented it, right, So the things that we think about 0:47:00.600 --> 0:47:02.799 a sci fi are just science that's not here yet. 0:47:02.880 --> 0:47:21.480 All right, Yeah, the future is now. So let's talk 0:47:21.520 --> 0:47:24.279 about losing memory a little bit as we wrap things up. 0:47:24.640 --> 0:47:27.440 So we talked about how your brain is working overnight 0:47:27.480 --> 0:47:31.080 to strengthen memories. How do we lose memories over time? 0:47:31.440 --> 0:47:33.160 So there's a number of different ways to do this. 0:47:33.680 --> 0:47:37.040 Memory can be lost because of decay, so just the 0:47:37.080 --> 0:47:40.200 passage of time a lot of times can make memories 0:47:40.280 --> 0:47:43.480 just harder to remember, harder to access. And we've known 0:47:43.520 --> 0:47:47.360 this since eighteen eighties. Herman Ebbinghouse was the first to 0:47:47.440 --> 0:47:50.560 kind of do this using experiments with himself. You would 0:47:50.680 --> 0:47:54.080 learn lists of nonsense syllables and then try to map 0:47:54.120 --> 0:47:57.200 his own forgetting curve. So how much forgetting happens over 0:47:57.200 --> 0:47:59.279 the first twenty four hours, next twenty four hours, next 0:47:59.280 --> 0:48:02.000 twenty four hours. Yeah, I know, experiments on yourself very 0:48:02.040 --> 0:48:04.480 very boring times in eighteen eighty so it didn't have 0:48:04.520 --> 0:48:06.520 too much else to do, so I did this with himself, 0:48:07.520 --> 0:48:09.920 but maps what's called the forgetting curve, which we still 0:48:09.960 --> 0:48:11.880 to this day. We can look at any sort of 0:48:11.880 --> 0:48:14.120 memory function or any memory task that we do in 0:48:14.160 --> 0:48:16.320 the lot and we see a very clear forgetting curve. 0:48:16.600 --> 0:48:18.600 A lot of forget the first twenty four hours. Then 0:48:18.600 --> 0:48:20.839 things to kind of taper off. So there's that, And 0:48:20.880 --> 0:48:24.440 the suspicion is that mostly it's decay, but sometimes it 0:48:24.480 --> 0:48:28.200 happens because of interference, because similar memories get in there 0:48:28.239 --> 0:48:30.760 and kind of interfere with one another, compete with one another, 0:48:30.960 --> 0:48:32.799 sort of the memory that you have for them get 0:48:32.800 --> 0:48:36.600 a little bit fuzzy. And again these are maybe features, 0:48:36.640 --> 0:48:39.240 not bugs, right where maybe the system is not intending 0:48:39.280 --> 0:48:42.160 to hold onto memories with high fidelity for long. So 0:48:42.239 --> 0:48:46.000 interference and decay help us extract what's most important and 0:48:46.120 --> 0:48:48.319 keep that over time, and then other things can kind 0:48:48.320 --> 0:48:50.920 of go away. So those are natural things that happen 0:48:50.920 --> 0:48:53.239 in every brain all the time, and there's nothing to 0:48:53.280 --> 0:48:55.919 be concerned about decay, interference, nothing to be concerned about. 0:48:56.080 --> 0:48:59.000 But as we get older, and by older I hate 0:48:59.000 --> 0:49:01.800 to say this, you know, talking about like forties. 0:49:01.400 --> 0:49:06.160 And above that what I wanted to hear money, Well, 0:49:06.200 --> 0:49:06.600 I'm going to. 0:49:06.640 --> 0:49:09.840 Say graduate in our fourth decade and then maybe a 0:49:09.840 --> 0:49:14.160 little bit more precipitously, over time, memory does get more difficult. 0:49:14.320 --> 0:49:18.160 So things do degrade, and we start to maybe lose 0:49:18.200 --> 0:49:20.960 to some extent, our ability to make new memories, encode 0:49:20.960 --> 0:49:23.520 new memories, our memories. For the old stuff is still 0:49:23.600 --> 0:49:25.600 there's still resilience, even though every now and then we 0:49:25.680 --> 0:49:28.520 might have a problem with access. So we get distracted, 0:49:28.560 --> 0:49:30.919 we lose retrieval cues, but you know it's there because 0:49:30.920 --> 0:49:33.840 if you get the right reminder, boom, it comes back. Right. 0:49:34.000 --> 0:49:36.000 It's just a matter of like tip of a tongue, 0:49:36.080 --> 0:49:38.440 you know, being able to remember exactly that the right 0:49:38.560 --> 0:49:41.360 queue for retrieval. That becomes more difficult when we're just 0:49:41.400 --> 0:49:44.760 more distracted. But as we get older, making new memories 0:49:44.760 --> 0:49:47.640 becomes harder. And then for some folks who might go 0:49:47.719 --> 0:49:52.080 down the trajectory to Alzheimer's disease, right then that becomes 0:49:52.320 --> 0:49:54.880 exceptionally more difficult. And that's one of the first things 0:49:54.920 --> 0:49:59.200 to go. And there's a very difficult line between what's 0:49:59.440 --> 0:50:02.280 normal I hate to say that word, maybe more typical 0:50:02.600 --> 0:50:05.960 age associated memory impairment, which you can expect in every brain, 0:50:06.480 --> 0:50:08.640 and that's something that may be a bit more costs 0:50:08.680 --> 0:50:10.879 for concern because it may be going down to about 0:50:10.880 --> 0:50:14.400 the Alzheimer's disease. Dissociating those two, say in the sixties 0:50:14.440 --> 0:50:17.120 and seventies, is actually very difficult. It's not very easy 0:50:17.360 --> 0:50:20.400 because both can start out as a form of forgetfulness. 0:50:20.920 --> 0:50:24.480 But with Alzheimer's disease or with dementia, it's very progressive, 0:50:24.840 --> 0:50:27.280 so it does get worse and worse and worse over time. 0:50:28.080 --> 0:50:30.680 That change in a healthy aging brain or a typical 0:50:30.680 --> 0:50:34.439 aging brain is far less deep, so you don't see 0:50:34.480 --> 0:50:37.200 too much changing over time. You don't see this degradation 0:50:37.280 --> 0:50:41.000 to the point where it becomes very noticeable by family, friends, neighbors, 0:50:41.160 --> 0:50:44.160 and so on. So those are the forms of memory 0:50:44.320 --> 0:50:48.000 loss or memory change that happened. Some totally innocuous, no 0:50:48.120 --> 0:50:50.440 cause for concern, they happen every day to everyone, to 0:50:50.480 --> 0:50:53.239 the best of us. And then some that are a 0:50:53.280 --> 0:50:54.640 bit more cause for concern. 0:50:54.719 --> 0:50:57.479 As we get older and mechanistically, is it just the 0:50:57.560 --> 0:51:01.759 messages are not getting sent between those anymore, or this is. 0:51:01.760 --> 0:51:04.760 Something we've done quite a bit of work on. Actually mechanistically, 0:51:04.800 --> 0:51:07.759 what seems to be the case is that first the 0:51:07.840 --> 0:51:10.200 part of the brain that's really important for encoding these 0:51:10.200 --> 0:51:13.600 episodic memories, the hippocampus, as I said, has a very 0:51:13.600 --> 0:51:17.520 interesting change and it's dynamic. So this is a massive 0:51:17.560 --> 0:51:19.880 information processing hub in the brain. Even though it's a 0:51:19.880 --> 0:51:24.200 small structure, it carries a big information processing load, and 0:51:24.640 --> 0:51:27.560 it kind of can shift its state from encoding new 0:51:27.560 --> 0:51:31.479 information to remembering old information. And there are a few 0:51:31.600 --> 0:51:34.480 changes that happen to the cells in that system as 0:51:34.520 --> 0:51:37.640 we get older that bias the system towards remembering old 0:51:37.640 --> 0:51:41.040 information and away from encoding new information. And there's lots 0:51:41.040 --> 0:51:43.520 of sort of reasons why that is, we tend to 0:51:44.040 --> 0:51:49.160 change the excitation inhibition balance, we tend to change neurotransmitter concentrations, 0:51:49.200 --> 0:51:50.800 all of those kinds of things as we get older 0:51:51.000 --> 0:51:54.799 that cause that change in the information processing balance. But 0:51:54.920 --> 0:51:57.440 the other thing that happens more in the context of 0:51:57.640 --> 0:52:01.520 Alzheimer's disease is you also start to deprive the hippocampus 0:52:01.560 --> 0:52:03.880 of its main input coming in from the rest of 0:52:03.920 --> 0:52:07.239 the brain. So there's a region that sits alongside the 0:52:07.320 --> 0:52:11.400 hippo campus called the antorhinal cortex, and that region shrivels 0:52:11.480 --> 0:52:14.720 up in Alzheimer's disease. It's one of the first regions 0:52:14.760 --> 0:52:18.719 to deposit what's called tangle pathology or tau tangles, and 0:52:18.760 --> 0:52:22.319 that's a marker of cell death. So there's massive cell 0:52:22.400 --> 0:52:25.080 loss that's happening in that's around cortex early on, which 0:52:25.160 --> 0:52:29.840 deprives the hippocampus of its principal inputs. So in computer 0:52:29.920 --> 0:52:32.640 science we have this old adage called garbage in garbage out, 0:52:33.360 --> 0:52:36.560 and that's essentially what's happening in the hippocampus. It's the 0:52:36.640 --> 0:52:39.680 quality of the information that's coming in starts to become 0:52:39.840 --> 0:52:42.759 much more degraded than the context of Alzheimer's c's, So 0:52:42.760 --> 0:52:45.080 we can't possibly expect it to do a good job 0:52:45.239 --> 0:52:48.920 encoding information and story with high fidelity if the information 0:52:49.000 --> 0:52:52.359 coming in is in some ways quote garbage. So that 0:52:52.760 --> 0:52:54.680 tends to be one of the things that is also 0:52:54.719 --> 0:52:57.680 mechanistically associated with memory loss in the aging brain. 0:52:57.920 --> 0:53:00.360 Do we know why that region starts to degree in 0:53:00.400 --> 0:53:01.480 some people and not others. 0:53:01.719 --> 0:53:05.319 You know, there's hypotheses and I have my pet hypothesies. 0:53:05.320 --> 0:53:07.719 In the field has its pet hypotheses and so on, 0:53:07.800 --> 0:53:10.799 But there's a variety of contributors. We suspect that in 0:53:10.840 --> 0:53:15.680 the context of Alzheimer's disease, it's a combination of inflammatory changes, 0:53:15.760 --> 0:53:19.080 so that the mirror immune system is disregulated in Alzheimer's disease, 0:53:19.080 --> 0:53:22.800 where the inflammatory response that normally is very healthy starts 0:53:22.800 --> 0:53:24.959 to kind of take a turn and become very pathological. 0:53:25.400 --> 0:53:28.080 There is vascular damage that happens as we get older, 0:53:28.080 --> 0:53:31.120 and we suspect that some of those early vascular insults, 0:53:31.160 --> 0:53:33.680 so related to blood flows, deifenning of the arteries and 0:53:33.719 --> 0:53:38.040 so on, can also contribute to that. There's metabolic regulation 0:53:38.200 --> 0:53:41.800 that changes, so the metabolic demands of different regions also 0:53:42.120 --> 0:53:45.480 becomes disregulated as we get older. And then one thing 0:53:45.520 --> 0:53:48.120 that we've worked quite a bit on is excitation inhibition 0:53:48.239 --> 0:53:51.759 balance and the notion that normally the brain keeps this 0:53:51.920 --> 0:53:56.480 dynamic beautifully between stop signals and ghost signals, and as 0:53:56.520 --> 0:54:00.560 we get older there actually is an overabunton of the 0:54:00.600 --> 0:54:05.160 ghost signals which can drive the brain pathologically more towards 0:54:05.200 --> 0:54:07.640 memory loss and not enough of the stop signals, so 0:54:08.080 --> 0:54:10.920 that imbalance can also be a contributor. So it's a 0:54:11.000 --> 0:54:13.880 multifactorial issue. There's lots of contributors. This is not just 0:54:14.040 --> 0:54:16.920 one single pathology kind of model, as much as some 0:54:17.000 --> 0:54:19.160 of the field likes to believe that. It's a bit 0:54:19.200 --> 0:54:19.840 more complex. 0:54:20.080 --> 0:54:21.719 So as someone who just learned that they're in the 0:54:21.760 --> 0:54:24.440 old category, I. 0:54:24.360 --> 0:54:26.799 Would necessarily call it that. I would just say, we're 0:54:26.800 --> 0:54:30.160 maybe done developing and we're now just kind of hitting 0:54:30.160 --> 0:54:32.320 that hump of we're going to start the aging process. 0:54:32.600 --> 0:54:34.120 Got it, got it, I'll think of it that way. 0:54:34.120 --> 0:54:38.200 But I like that better. What kinds of science based 0:54:38.680 --> 0:54:40.920 things can we do to maintain our memory? So I 0:54:41.000 --> 0:54:43.120 see all these apps, pitch me, is there any science 0:54:43.160 --> 0:54:44.200 behind any of those things? 0:54:45.200 --> 0:54:47.960 Well, the app stuff probably not. I will tell you 0:54:48.040 --> 0:54:51.000 that the four big things that are really really important, 0:54:51.040 --> 0:54:53.279 and when I say really important, I mean they are 0:54:53.320 --> 0:54:57.680 supported both by epideological data and by clinical trials. So 0:54:57.760 --> 0:54:59.600 these things are really really helpful. The first one is 0:54:59.640 --> 0:55:03.600 physical activity. We know that physical activity maintains brain health 0:55:03.640 --> 0:55:06.600 well into older adulthood. We know that it can delay 0:55:06.640 --> 0:55:09.360 the onset of Alzheimer's disease. It can make the outcomes 0:55:09.400 --> 0:55:13.000 better for patients and as protective it really is knocking out. 0:55:13.040 --> 0:55:16.560 So sedentary lifestyle is a risk factor. We've done work 0:55:16.600 --> 0:55:19.719 also to show that even activity as brief as ten 0:55:19.719 --> 0:55:22.880 minutes of walking can be helpful to memory. So it 0:55:22.920 --> 0:55:25.160 doesn't take a lot, you know, I would say thirty 0:55:25.200 --> 0:55:27.960 minutes of you know, mild to moderate activity like walking, 0:55:28.320 --> 0:55:31.560 risk walking, that's sufficient to be able to give people 0:55:32.080 --> 0:55:34.440 a way to handle that risk factory. The second thing 0:55:34.520 --> 0:55:36.680 that's really important, and this kind of goes back to 0:55:36.680 --> 0:55:40.200 your idea about apps and kind of cognitive engagement. It 0:55:40.239 --> 0:55:42.319 turns out that apps and brain games on all of 0:55:42.360 --> 0:55:45.720 that efficacy is a little bit tendless, so there's conflicting reports. 0:55:46.080 --> 0:55:49.560 But we know that social engagement is really important. So 0:55:49.600 --> 0:55:52.439 in other words, if you remove social engagement, if folks 0:55:52.440 --> 0:55:55.680 become isolated the same past retirement, that's a risk factory 0:55:55.800 --> 0:55:58.719 for sure. But if they're able to continue to be 0:55:58.800 --> 0:56:02.840 social build archer social networks in person, you know, volunteering, 0:56:02.880 --> 0:56:06.280 community centers, churches, synagogues, whatever it is, or being around 0:56:06.320 --> 0:56:10.200 people in general, and that can also combine with physical activity. 0:56:10.280 --> 0:56:13.320 So let's say it's dance class now, it's physical activity 0:56:13.360 --> 0:56:16.440 and social contact. Right, those kinds of things, even in 0:56:16.440 --> 0:56:19.240 interventional studies, have been shown to have very positive results. 0:56:19.880 --> 0:56:23.120 Then the third piece is diet. A heart healthy diet 0:56:23.160 --> 0:56:25.520 is a brain healthy diet. And the one that has 0:56:25.560 --> 0:56:28.440 been tried and true in clinical trials is the Mediterranean diet. 0:56:28.960 --> 0:56:31.160 So the Mediterranean which has lots and lots of variants, 0:56:31.200 --> 0:56:34.640 but I think very colorful, leafy, green vegetables and so on, 0:56:35.160 --> 0:56:39.040 healthy fats, and reducing you know, things like red meat 0:56:39.080 --> 0:56:41.439 and some on. So that one also has been tried 0:56:41.480 --> 0:56:44.440 in clinical trials compared to other diets and seems to 0:56:44.600 --> 0:56:47.600 be able to stave off risk. And then the last piece, 0:56:47.680 --> 0:56:49.920 which I think is one of the most important, to sleep. 0:56:50.640 --> 0:56:54.000 We all need good quality and quantity of sleep every night. 0:56:54.080 --> 0:56:57.439 It turns out that actually during sleep we go through 0:56:57.440 --> 0:56:59.800 a process of glymphatic clearance and we clear out on 0:56:59.800 --> 0:57:01.960 the life lot of the pathologies that can lead down 0:57:02.000 --> 0:57:04.480 the path to Alzheimer's. These or at least be contributors 0:57:04.520 --> 0:57:08.160 to it. And studies have shown that if you have 0:57:08.280 --> 0:57:11.160 sleep loss folks for example, who sleep less than six 0:57:11.200 --> 0:57:13.239 hours a night versus those who sleep more than seven 0:57:13.320 --> 0:57:16.720 or eight hours there's differences in their amyloid uptakes, so 0:57:16.960 --> 0:57:19.520 that emiloid pathology is one of the chief pathology in 0:57:19.560 --> 0:57:21.880 Alzheimer's disease. You see a lot more of it in 0:57:21.920 --> 0:57:24.560 those who sleep those fewer hours, and a lot less 0:57:24.560 --> 0:57:27.640 of it and those who sleep longer. So sleep disruption, 0:57:27.800 --> 0:57:30.960 sleep loss, that's a risk factor. The good news is 0:57:31.120 --> 0:57:34.920 most sleep problems are treatable, whether it's because of obstructive 0:57:34.920 --> 0:57:38.280 sleep apnea, or insomnia or any other reason, restless slag, 0:57:38.520 --> 0:57:40.560 all of those things. There's good treatments out there that 0:57:40.600 --> 0:57:43.400 will help people sleep better. So those are the four 0:57:43.520 --> 0:57:45.600 sort of chief things. There's many other smaller things, but 0:57:45.880 --> 0:57:47.520 those are the four ones that I like to lead 0:57:47.600 --> 0:57:50.440 with because they have just excellent data in their favor. 0:57:50.680 --> 0:57:53.120 Well, I'm excited about the sleep thing. I like sleeping. 0:57:54.120 --> 0:57:56.200 Maybe it's time to get out and exercise a little 0:57:56.240 --> 0:57:59.320 more so. My co host is a physicist. He always 0:57:59.400 --> 0:58:03.160 ends on a aliens. So here we go. If an 0:58:03.160 --> 0:58:05.600 alien were to land on Earth today, do you think 0:58:05.640 --> 0:58:07.760 they would store memories in a similar way. 0:58:08.120 --> 0:58:09.840 You know, if you had asked me that question ten 0:58:09.920 --> 0:58:11.960 years ago, I would have said, yes, I think our 0:58:11.960 --> 0:58:15.600 memory system is exceptional. It's wonderful, it's brilliant. Why not 0:58:15.960 --> 0:58:18.240 they should be like a model to strive to achieve. 0:58:19.000 --> 0:58:20.960 But I will take the opportunity since we've got a 0:58:20.960 --> 0:58:23.360 couple more minutes, Kelly, and tell you about something that 0:58:23.840 --> 0:58:27.000 changes my answer to this question. And that is the 0:58:27.040 --> 0:58:30.160 discovery that was made first by James Magaw who is 0:58:30.240 --> 0:58:33.480 the founding director of my center here at uc Aervine, 0:58:33.600 --> 0:58:35.720 and we continue to do work with this group of 0:58:35.800 --> 0:58:40.480 remarkable individuals who have what's called highly superior autobiographical memory. 0:58:41.360 --> 0:58:43.439 We spent a lot of time during this conversation talking 0:58:43.480 --> 0:58:46.800 about how memory is fallible. There's forgetting, there's interference. It's 0:58:46.840 --> 0:58:49.919 not meant to store everything with high fidelity because that's 0:58:49.960 --> 0:58:52.919 going to compromise your knowledge generation and so on. Well, 0:58:52.960 --> 0:58:56.400 these folks would beg to differ. And it's incredible because 0:58:56.440 --> 0:58:59.000 they do store things with high fidelity. They can remember 0:58:59.200 --> 0:59:01.160 everything that happened in our lives since that they were 0:59:01.200 --> 0:59:04.240 teenagers and tell you exactly what happened on what day 0:59:04.240 --> 0:59:07.160 of the week, what month, and someone. And they don't 0:59:07.200 --> 0:59:11.360 have a problem extracting generalities and knowledge. Also, So sometimes 0:59:11.360 --> 0:59:12.960 I'll jup with them and say I think you're like 0:59:13.040 --> 0:59:17.000 the X men of our generation, X people of our generation. 0:59:17.400 --> 0:59:19.600 It's remarkable and we still don't understand how they do 0:59:19.680 --> 0:59:22.520 it and how their brains are wired differently. So if 0:59:22.520 --> 0:59:26.520 aliens sufficiently advanced to aliens, I think, if they're reaching 0:59:26.560 --> 0:59:29.120 Earth before we reach them, they're probably far more advanced 0:59:29.160 --> 0:59:31.600 than us. They're more likely to have figure it out 0:59:31.640 --> 0:59:34.360 a way to do that which sort of combines the 0:59:34.400 --> 0:59:37.480 best of what we have built into our computers and 0:59:37.520 --> 0:59:40.360 what we have built into our brains. Just no compromise, 0:59:40.440 --> 0:59:41.360 no sacrifice. 0:59:41.640 --> 0:59:44.120 Awesome. Well, I wish Daniel we're here to hear that, 0:59:44.280 --> 0:59:46.480 but I'm sure he'll enjoy hearing that explanation when he 0:59:46.480 --> 0:59:48.760 gets back. Thank you so much for your time, Mike. 0:59:48.840 --> 0:59:50.280 This was absolutely fascinating. 0:59:50.360 --> 0:59:52.640 They're very welcome. I very much enjoyed to Kelly. Thank you. 1:00:00.120 --> 1:00:03.880 Daniel and Kelly's Extraordinary Universe is produced by iHeartRadio. 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