Huberman Lab - Dr. Terry Sejnowski: How to Improve at Learning Using Neuroscience & AI
Episode Date: November 18, 2024In this episode, my guest is Dr. Terry Sejnowski, Ph.D., professor of computational neurobiology at the Salk Institute for Biological Studies. He is world-renowned for exploring how our brain processe...s and stores information and, with that understanding, for developing tools that enable us to markedly improve our ability to learn all types of information and skills. We discuss how to learn most effectively in order to truly master a subject or skill. Dr. Sejnowski explains how to use AI tools to forage for new information, generate ideas, predict the future, and assist in analyzing health data and making health-related decisions. We also explore non-AI strategies to enhance learning and creativity, including how specific types of exercise can improve mitochondrial function and cognitive performance. Listeners will gain insights into how computational methods and AI are transforming our understanding of brain function, learning, and memory, as well as the emerging roles of these tools in addressing personal health and treating brain diseases such as Alzheimer’s and Parkinson’s. Access the full show notes for this episode at hubermanlab.com. Pre-order Andrew's new book, Protocols: protocolsbook.com Thank you to our sponsors AG1: https://drinkag1.com/huberman BetterHelp: https://betterhelp.com/huberman Helix Sleep: https://helixsleep.com/huberman David Protein: https://davidprotein.com/huberman LMNT: https://drinklmnt.com/huberman Joovv: https://joovv.com/huberman Timestamps 00:00:00 Dr. Terry Sejnowski 00:02:32 Sponsors: BetterHelp & Helix Sleep 00:05:19 Brain Structure & Function, Algorithmic Level 00:11:49 Basal Ganglia; Learning & Value Function 00:15:23 Value Function, Reward & Punishment 00:19:14 Cognitive vs. Procedural Learning, Active Learning, AI 00:25:56 Learning & Brain Storage 00:30:08 Traveling Waves, Sleep Spindles, Memory 00:32:08 Sponsors: AG1 & David 00:34:57 Tool: Increase Sleep Spindles; Memory, Ambien; Prescription Drugs 00:42:02 Psilocybin, Brain Connectivity 00:45:58 Tool: ‘Learning How to Learn’ Course 00:49:36 Learning, Generational Differences, Technology, Social Media 00:58:37 Sponsors: LMNT & Joovv 01:01:06 Draining Experiences, AI & Social Media 01:06:52 Vigor & Aging, Continued Learning, Tool: Exercise & Mitochondrial Function 01:12:17 Tool: Cognitive Velocity; Quick Stressors, Mitochondria 01:16:58 AI, Imagined Futures, Possibilities 01:27:14 AI & Mapping Potential Options, Schizophrenia 01:30:56 Schizophrenia, Ketamine, Depression 01:36:15 AI, “Idea Pump,” Analyzing Research 01:42:11 AI, Medicine & Diagnostic Tool; Predicting Outcomes 01:50:04 Parkinson’s Disease; Cognitive Velocity & Variables; Amphetamines 01:59:49 Free Will; Large Language Model (LLM), Personalities & Learning 02:12:40 Tool: Idea Generation, Mind Wandering, Learning 02:18:18 Dreams, Unconscious, Types of Dreams 02:22:56 Future Projects, Brain & Self-Attention 02:31:39 Zero-Cost Support, YouTube, Spotify & Apple Follow & Reviews, Sponsors, YouTube Feedback, Protocols Book, Social Media, Neural Network Newsletter Disclaimer & Disclosures
Transcript
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Welcome to the Huberman Lab Podcast,
where we discuss science
and science-based tools for everyday life.
I'm Andrew Huberman,
and I'm a professor of neurobiology and ophthalmology
at Stanford School of Medicine.
My guest today is Dr. Terry Signewski.
Dr. Terry Signewski is a professor
at the Salk Institute for Biological Studies,
where he directs the Computational Neurobiology Laboratory.
And as his title suggests,
he is a computational neuroscientist.
That is, he uses math,
as well as artificial intelligence and computing methods
to understand this overarching, ultra important question
of how the brain works.
Now, I realize that when people hear terms
like computational neuroscience, algorithms,
large language models, and AI,
that it can be a bit overwhelming and even intimidating.
But I assure you that the purpose of Dr. Sienowski's work,
and indeed today's discussion,
is all about using those methods
to clarify how the brain works,
and indeed to simplify the answer to that question.
So for instance, today you will learn
that regardless of who you are,
regardless of your
experience, that all your motivation in all domains of life is governed by a simple algorithm
or equation.
Dr. Signowski explains how a single rule, a single learning rule drives all of our motivation
related behaviors.
And it of course relates to the neuromodulator dopamine.
And if you're familiar with dopamine as a term, today, you will really understand how dopamine works to drive your levels of motivation or,
in some cases, lack of motivation and how to overcome that lack of motivation.
Today, we also discuss how best to learn. Dr. Sidenowski shares not just information about how
the brain works, but also practical tools that he and colleagues have developed, including a zero cost online portal
that teaches you how to learn better
based on your particular learning style.
The way that you in particular forge for information
and implement that information.
Dr. Signowski also explains how he himself
uses physical exercise of a particular type
in order to enhance his cognition,
that is his brain's ability to learn information
and to come up with new ideas.
Today, we also discuss both the healthy brain
and the diseased brain
in conditions like Parkinson's and Alzheimer's
and how particular tools that relate
to mitochondrial function can perhaps be used
in order to treat various diseases,
including Alzheimer's dementia.
I'm certain that by the end of today's episode,
you will have learned a tremendous amount of new knowledge
about how your brain works and practical tools
that you can implement in your daily life.
Before we begin, I'd like to emphasize that this podcast
is separate from my teaching and research roles
at Stanford.
It is however, part of my desire and effort
to bring zero cost to consumer information about science
and science related tools to the general public.
In keeping with that theme, I'd like to thank the sponsors of today's podcast.
Our first sponsor is BetterHelp.
BetterHelp offers professional therapy with a licensed therapist carried out completely
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I've been doing weekly therapy for well over 30 years.
Initially I didn't have a choice.
It was a condition of being allowed to stay in school, but pretty soon I realized that
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And now for my discussion with Dr. Terry Sienowski.
Dr. Terry Sienowski, welcome.
Great to be here.
We go way back.
And I'm a huge, huge fan of your work because you've worked on a great many different things
in the field of neuroscience.
You're considered by many a computational neuroscience, so you bring mathematical models
to an understanding of the brain and neural networks.
And we're also going to talk about AI today, and we're going to make it accessible for
everybody, biologist or no, math background or no.
To kick things off, I want to understand something.
I understand a bit about the parts list of the brain
and most listeners of this podcast
will understand a little bit of the parts list of the brain,
even if they've never heard an episode of this podcast
before because they understand there are cells,
those cells are neurons,
those neurons connect to one another in very specific ways that allow us to see, to hear, to think, et cetera.
But I've come to the belief that even if we know the parts list, it doesn't really inform
us how the brain works.
This is the big question.
How does the brain work?
What is consciousness?
All of this stuff.
So where and how does an understanding
of how neurons talk to one another
start to give us a real understanding
about like how the brain works?
Like what is this piece of meat in our heads?
Because it can't just be,
okay, the hippocampus remembers stuff
and the visual cortex perceives stuff.
When you sit back and you remove the math
from the mental conversation, if that's possible for you,
how do you think about quote unquote, how the brain works?
Like at a very basic level,
what is this piece of meat in our heads
really trying to accomplish?
From let's just say the time when we first wake up
in the morning and we're a little groggy
till we make it to that first cup of coffee or water, or maybe even just to urinate first
thing in the morning.
What is going on in there?
What a great question.
I have a, Pat Churchlin and I wrote a book, Compute Our Brain, and in it there's this
levels diagram.
Levels of investigation at different spatial scales from the molecular at the very bottom
to synapses and neurons, circuits, neural circuits, how they're connected with each
other and then brain areas and the cortex and then the whole central nervous system span 10 orders of magnitude,
you know, 10th to the 10th in spatial scale.
So you know, where is consciousness in all of that?
So there are two approaches that neuroscientists have taken.
I shouldn't say neuroscientists, I should say that scientists have taken.
And the one you described, which is,
let's look at all the parts, that's the bottom up approach.
Take it apart and just reductionist approach.
And you make a lot of progress.
You can figure out how things are connected
and understand how development works, how neurons connect.
But it's very difficult to really make progress
because quickly you get
lost in the forest.
Now the other approach, which has been successful but at the end unsatisfying is the top down
approach. And this is the approach that psychologists have taken looking at behavior and trying to understand the laws of behavior.
This is the behaviorists.
But even people in AI were trying
to do a top-down, to write programs that
could replicate human behavior, intelligent behavior.
And I have to say that both of those approaches, bottom-up
or top-down, have really not gotten to the core of that both of those approaches, bottom up or top down, have really not gotten
to the core of answering any of those questions, the big questions.
But there's a whole new approach now that is emerging in both neuroscience and AI at
exactly the same time.
At this moment in history, it's really quite remarkable.
So there's an intermediate level between the implementation
level at the bottom, how you implement
some particular mechanism.
And the actual behavior of the whole system
is called the algorithmic level.
It's in between.
So algorithms are like recipes.
They're like when you bake a cake,
you have to have ingredients and you have to say
the order in which they're put together and how long.
And, you know, if you get it wrong, you know,
it doesn't work, you know, it's just a mess.
Now, it turns out that we're discovering algorithms.
We've made a lot of progress with understanding the algorithms that are used in neural circuits.
And this speaks to the computational level of how to understand the function of the neural
circuit.
But I'm going to give you one example of an algorithm, which is one we worked on back in the 1990s when
Peter Dayan and Reed Montague were postdocs in the lab.
And it had to do with a part of the brain below the cortex called the basal ganglia,
which is responsible for learning sequences of actions in order to achieve some goal.
For example, if you want to play tennis, you have to be able to coordinate many muscles
and a whole sequence of actions has to be made if you want to be able to serve accurately
and you have to practice, practice, practice.
Well what's going on there is that the basal ganglia basically is taking over from the cortex and
producing actions that get better and better and better and better.
And that's true not just of the muscles, but it's also true of thinking.
If you want to become good in any area, if you want to become a good financier, if you
want to become a good doctor or neuroscientist, right?
You have to be practicing, practicing, practicing in terms of understanding what's the details
of the profession and what works, what doesn't work and so forth.
And it turns out that the spacial ganglia interacts with the cortex, not just in the
back, which is the action part, but also with not just in the back, which is the action part,
but also with the prefrontal cortex,
which is the thinking part.
Can I ask you a question about this briefly?
The basal ganglia, as I understand,
are involved in the organization
of two major types of behaviors,
go, meaning to actually perform a behavior,
but the basal ganglia also instruct no-go.
Don't engage in that behavior.
And learning an expert golf swing or even a basic golf swing or tennis racket swing involves both of
those things, go and no-go. Given what you just said, which is that the basal ganglia are also
involved in generating thoughts of particular kinds, I wonder therefore if it's also involved
in suppression of thoughts of particular kinds.
I mean, you don't want your surgeon cutting into,
you know, a particular region
and just thinking about their motor behaviors,
what to do and what not to do.
They presumably need to think about what to think about,
but also what to not think about.
You don't want that surgeon thinking about
how their kid was a brat that morning, and
they're frustrated because the two things interact.
So is there go, no go in terms of action and learning, and is there go, no go in terms
of thinking?
Well, I mentioned the prefrontal cortex and that part, the loop with the basal ganglia,
that is one of the last to mature in early adulthood. And the problem is that for adolescents,
it's not the no-go part for planning and actions.
This isn't quite there yet.
And so often, it doesn't kick in to prevent you
from doing things that are not in your best interest.
So yes, absolutely right.
But one of the things, though, is that learning is involved.
And this is really a problem that we cracked,
first theoretically in the 90s, and then experimentally later
by recording from neurons and also brain imaging in humans.
So it turns out we know the algorithm that
is used in the brain for how to learn sequences of actions to achieve a goal.
And it's the simplest possible algorithm you can imagine. It's simply to predict the next
reward you're going to get. If I do an action, will it give me something of value? And you learn
every time you try something,
whether you got the amount of reward you expected or less,
you use that to update the synapses, synaptic plasticity,
so that the next time you'll have a better chance
of getting a better reward, and you build up
what's called a value function.
And so the cortex now, over your lifetime,
is building up a lot of knowledge about things
that are good for you, things that are bad for you.
Like you go to a restaurant, you order something, how do you know what's good for you?
You've had lots of meals in a lot of places, and now that is part of your value function.
This is the same algorithm that was used by AlphaGo.
This is the program that DeepMind built.
This is an AI program that beat the world Go champion.
And Go is the most complex game that humans have ever played on a regular basis.
Far more complex than chess, as I understand.
Yeah, that's right.
So Go is to chess with chesses to something like checkers.
In other words, the level of difficulty
is another way off above it
because you have to think in terms of battles
going on all over the place at the same time.
And the order in which you put the pieces down
are gonna affect what's gonna happen in the future.
So this value function is super interesting.
And I wonder whether, and I think you answered this,
but I wonder whether this value function
is implemented over long periods of time.
So you talked about the value function
in terms of learning a motor skill.
Let's say swinging a tennis racket
to do a perfect tennis serve
or even just a decent tennis serve.
When somebody goes back to the court, let's say on the weekend, once a month over the
course of years, are they able to tap into that same value function every time they go
back even though there's been a lot of intervening time and learning?
That's question number one.
And then the other question is, do you think that this value function is also being played
out in more complex scenarios, not just motor learning, such as, let's say, a domain of
life that for many people involves some trial and error, it would be like human relationships.
We learn how to be friends with people.
We learn how to be a good sibling. We learn how to be a good sibling.
We learn how to be a good romantic partner. We get some things right, we get some things wrong. So it's the same value function being implemented. We're paying attention to what was rewarding.
But what I didn't hear you say also was what was punishing. So are we only paying attention to what
is rewarding or we're also integrating punishment? We don't get an electric shock when we get the serve wrong,
but we can be frustrated.
What you identified is some very important feature,
which is that rewards, by the way,
every time you do something,
you're updating this value function every time
and it accumulates and the answer to your first question,
the answer is that it's always going to be there.
It doesn't matter.
It's a very permanent part of your experience and who you are.
And interestingly, and the behaviorists knew this back in the 1950s, that you can get there
two ways of trial and error.
Small rewards are good because you're constantly coming closer and closer to getting what you're
seeking, better tennis player or being able to make a friend.
But the negative punishment is much more effective.
One trial learning.
You don't need to have 100 trials, which you need when you're training a rat to do some
tasks with small food rewards.
But if you just shock the rat, boy, that rat doesn't forget that.
Yeah, one really bad relationship
will have you learning certain things forever.
And this is also PTSD, post-traumatic stress disorder,
is another good example of that.
That can screw you up for the rest of your life.
So, but the other thing,
and you pointed out something really important,
which is that a large part of the prefrontal cortex is devoted to social interactions.
And this is how humans, you know, when you come into the world, you don't know what language
you're going to be speaking.
You don't know what the cultural values are, that you're going to have to be able to become
a member of this society and as things that are expected of you, all of that has
to become through experience, through building this value function.
So this is, and this is something we discovered in the 20th century and now it's going into
AI.
It's called reinforcement learning in AI.
It's a form of procedural learning as opposed to the cognitive level where you think and
you do things, cognitive thinking is much
less efficient because you have to go step by step with procedural learning.
It's automatic.
Can you give me an example of procedural learning in the context of a comparison to cognitive
learning?
Like, is there an example of perhaps like how to make a decent cup of coffee using,
you know, purely knowledge-based learning versus procedural learning?
Okay, okay.
Where procedural learning wins.
And I can imagine one, but you're the true expert here.
Well, you know, you know a lot of examples, but my, since we've been talking about tennis,
can you imagine learning how to play tennis through a book, reading a book?
That's so funny.
On the plane back from Nashville yesterday,
the guy sitting across the aisle from me
was reading a book about,
maybe he was working on his pilot's license or something.
And I looked over and couldn't help
but notice these diagrams of the plane flying.
And I thought, I'm just so glad that this guy is a passenger
and not a pilot.
And then I thought about how the pilots learned.
And presumably it was a combination
of practical learning and textbook learning.
I mean, when you scuba dive, this is true.
I'm scuba dive certified.
And when you get your certification,
you learn your dive tables
and you learn why you have to wait between dives, et cetera,
and gas exchange and a number of things,
but there's really no way to simulate
what it is to take your mask off underwater,
put it back on, and then, you know,
blow the water out of your mask.
Like that, you just have to do that in a pool,
and you actually have to do it when you need to
for it to really get drilled in.
Yes, you, you, you, you, you, you,
it's really essential for things
that have to be executed quickly and expertly to get
that really down pat so you don't have to think.
And this happens in school, right?
In other words, you have classroom lessons where you're given explicit instruction, but
then you go do homework.
That's procedural learning.
You do problems.
You solve problems.
And, you know, I'm a PhD physicist, so I went through all of the classes, you know, in theoretical
physics.
And it was really the problems that really were the core of becoming a good physicist.
You know, you can memorize the equations, but that doesn't mean you understand how to use the equations.
I think it's worth highlighting something.
A lot of times on this podcast, we talk about what I call protocols.
It would be like get some morning sunlight in your eyes to stimulate your super chiasmatic
nucleus by way of your retinal ganglion cells.
Audiences of this podcast will recognize those terms.
It's basically get sunlight in your eyes in the morning and set your circadian clock.
You can hear that a trillion times, but I do believe that there's some value to both
knowing what the protocol is, the underlying mechanisms.
There are these things in your eye that encode the sunrise qualities of light, et cetera,
and then send them to your brain, et cetera, et cetera.
Then once we link knowledge, pure knowledge, to a practice, I do believe that the two things
merge someplace in a way that, let's say, reinforces both the knowledge and the practice.
So these things are not necessarily separate.
They bridge.
In other words, doing your theoretical physics problem sets reinforces the examples that
you learned in lecture and in your textbooks and vice
versa.
So this is a battle that's going on right now in schools.
What you've just said is absolutely right.
You need both.
We have two major learning systems.
We have a cognitive learning system, which is cortical.
We have a procedural learning system, which is subcortical, basal ganglia.
And the two go hand in hand.
If you want to become good at anything, the two are going to help each other.
And what's going on right now in schools, in California at least, is that they're trying
to get rid of the procedural.
That's ridiculous.
They don't want students to practice because it's going to be, you're stressing them.
You don't want them to feel that they're having difficulty.
But we can do everything.
For those listening, I'm covering my eyes
because I mean, this would be like saying,
goodness, there's so many examples.
Like here's a textbook on swimming
and then you're gonna go out to the ocean someday,
and you will have never actually swum.
Right.
And now you're expected to be able to survive,
let alone swim well.
It's crazy, it's crazy.
But I'll tell you, Barbara Oakley has,
and I have a MOOC, Massive Open Online Course,
on learning how to learn.
And it helps students, we aimed it at students,
but it actually has been taken by 4 million people
in 200 countries, ages 10 to 90.
What is this called?
Learning how to learn.
Is it, is there a paywall?
No, it's free, completely free.
Amazing.
And you know, I get incredible feedback, you know, fan letters almost every day. Well, you're about I get incredible feedback,
you know, fan letters almost every day.
Well, you're about to get a few more.
Okay, well.
I did an episode on learning how to learn
and my understanding of the research
is that we need to test ourselves on the material.
The testing is not just a form of evaluation.
It is a form of identifying the errors
that help us then compensate for the errors and learn. Exactly.
But it's very procedural.
It's not about just listening and regurgitating.
You put your finger on it, which is that,
and this is what we teach the students,
is that you have to, the way the brain works, right,
is not, it doesn't memorize things like a computer,
but it has to be active learning.
You have to actively engage.
In fact, when you're, you're trying to solve a problem on your own, right, this is where
you're really learning by trial and error, and that's the procedural system.
But if someone tells you what the right answer is, you know, you know, that's just something
that is a fact that it gets stored away somewhere, but
it's not going to automatically come up if you actually are faced with something that's
not exactly the same problem, but is similar.
And by the way, this is the key to AI, completely essential for the recent success of these
large language models that the public now is beginning to use,
is that they're not parrots.
They just don't memorize what data they've taken in.
They have to generalize.
That means to be able to do well on new things that come in that are similar to the old things that you've seen,
but allow you to solve new problems.
That's the key to the brain. the old things that you've seen, but allow you to solve new problems.
That's the key to the brain.
The brain is really, really good at generalizing.
In fact, in many cases, you only need one example to generalize.
Like going to a restaurant for the first time, there are a number of new interactions.
There might be a host or a hostess.
You sit down at these tables you never sat at, somebody asks you questions, you read
it.
Okay, maybe it's a QR code these days, but forever after you understand the process of
going into a restaurant, it doesn't matter what the genre of food happens to be or what
city, sitting inside or outside, you can pretty much work it out.
Sit at the counter, sit outside, sit at the table.
There are a number of key action steps that I think pretty much translate to everywhere,
unless you go to some super high-end thing or some super low-end thing where it's a buffet
or whatever.
You can start to fill in the blanks here.
If I understand correctly, there's an action function that's learned from the knowledge and the experience.
Exactly.
And then where is that action function stored?
Is it in one location in the brain or is it kind of an emergent property of multiple brain
areas?
So you're right at the cusp here of where we are in neuroscience right now.
We don't know the answer to that question. In the past, it had been thought that the cortex were like countries, that each of which,
each part of the cortex was dedicated to one function.
Interestingly, you record for the neurons, and it certainly looks that way.
In other words, there's a visual cortex in the back, and there's a whole series of areas,
and then there's an auditory cortex here in the middle, and then the prefrontal cortex
for social interaction.
And so it looks really clear-cut that it's modular.
And now we're facing is we have a new way to record from neurons.
Optically, we can record from tens of thousands,
from dozens of areas simultaneously.
And what we're discovering is that if you want to do any task,
you're engaging not just the area that you might think
has the input coming in, say, the visual system,
but the visual system is getting say, the visual system. But the visual system is getting input
from the motor system, right?
In fact, there's more input coming from the motor system
than from the eye.
Really?
Yes.
Ann Churchland at UCLA has shown that in the mouse.
So now we're looking at global interactions
between all these areas.
And that's where real complex cognitive behaviors emerge.
It's from those interactions.
And now we have the tools for the first time to actually be able to see them in real time.
And we're doing that now first on mice and monkeys, but we now can do this in humans.
So I've been collaborating with a group at Mass General Hospital to record from people
with epilepsy, and they have to have an operation for people who are drug resistant, to be able
to take out, find out where it starts in the cortex, you know, where it is initiated, where
the seizure starts, and then to go in, you have to go in and record
simultaneously from a lot of parts of the cortex for weeks until you find out where
it is and then you go in and you try to take it out.
And often that helps.
Very, very invasive.
But for two weeks we have access to all those neurons in that cortex that are being recorded from constantly.
And so I've used, I started out because I was interested in sleep and I wanted to understand
what happens in the cortex of a human during sleep.
But then we realized that you can also figure, people who have these debilitating problems
with seizures,
you know, they're there for two weeks and they have nothing to do,
so they just love the fact that scientists are interested in helping them
and, you know, teaching them things and finding out where in the cortex
things are happening when they learn something.
This is a gold mine. It's unbelievable.
And I've learned things from humans that I could have never gotten from any other species.
Obviously, language is one of them.
But there are other things in sleep that we've discovered having to do with traveling waves.
There are circular traveling waves that go on during sleep, which is astonishing.
Nobody ever really saw that before.
But now-
If you were to ascribe one or two major functions to these traveling waves, what do you think
they are accomplishing for us in sleep?
And by the way, are they associated with deep sleep, slow wave sleep, or with rapid eye
movement sleep, or both?
This is non-REM sleep.
This is a jargon.
This is during intermediate-
Transition states. Transition states.
Transition state.
Our audience will probably be,
they've heard a lot about slow wave sleep
from me and Matt Walker from rapid eye movements.
This is light slow wave sleep, yeah.
And so what do these traveling waves accomplish for us?
Okay, so in the case of the,
they're called sleep spindles.
They last, the waves last for about a second or two
and they travel, like I say, in a circle around the cortex.
And it's known that these spindles are important
for consolidating experiences you've had during the day
into your long-term memory storage.
So it's a very important function,
and if you take out, see, it's the hippocampus
that is replaying the experiences.
It's a part of the brain.
It's very important for long-term memory.
If you don't have a hippocampus, you can't learn new things.
That is to say, you can't remember what you did yesterday,
or for that matter, even an hour earlier.
But the hippocampus plays back your experiences,
causes the sleep spindles now to need that into the cortex. And it's important you do
that right because you don't want to overwrite the existing knowledge you
have. You just want to basically incorporate the new experience into your
existing knowledge base in an efficient way that doesn't interfere with what
you already know. So that's an example of a very important
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As I recall, there are one or two things
that one can do in order to ensure
that one gets sufficient sleep spindles at night and thereby
incorporate this new knowledge. This was from the episode that we did with Gina Poe from UCLA,
I believe, and others, including Matt Walker. My recollection is that the number one thing is to
make sure you get enough sleep at night so you experience enough of these spindles.
Right, right.
And we're all familiar with the cognitive challenges, including memory challenges and
learning challenges associated with lack of sleep, insufficient sleep.
But the other was that there was some interesting relationship between daytime exercise and
nighttime prevalence of sleep spindles.
Are you familiar with that literature?
Yes, oh yes.
Yeah?
No, this is a fascinating literature and it's all pointing the same direction, which
is that we always neglect to appreciate the importance of sleep.
I mean, obviously, you're refreshed when you wake up, but there's a lot of things happen.
It's not that your brain turns off, it's that it goes into a completely different state,
and memory consolidation is just one of those things that happens when you fall asleep.
And of course, you know, there's dreams and so forth.
We don't fully appreciate or understand exactly how all the different sleep stages work together. Exercise is a particularly important part of getting the motor system tuned up.
And it's thought that the REM, rapid eye movement sleep, may be involved in that.
So that's yet another part of the sleep stages.
You go through, you go back and forth between dream sleep and the slow-wave sleep, back
and forth, back and forth during the night.
And then when you wake up, you're in the REM stage, more and more REM, more and more REM.
But that's all observation.
But as a scientist, what you want to do is perturb the system and see if you can, maybe
if you had more sleep spindles,
maybe you'd be able to remember things better. So it turns out Sarah Mednick, who was at
UC Irvine, did this fantastic experiment. So it turns out there's a drug called Zolpedim,
which goes by the name Ambien. You may have some experience with that.
I've never taken it, but I'm aware of what it is.
People use it as a sleep aid.
That's right.
A lot of people take it in order to sleep.
Okay.
Well, it turns out that it causes more sleep spindles.
Really?
Yeah, it doubles the number of sleep spindles.
If you take the drug,
Really? Yeah.
It doubles the number of sleep spindles.
If you take the drug, after you've done the learning, you do the learning at night, and
then you take the drug and you have twice as many spindles.
You wake up in the morning, you can remember twice as much from what you learned.
And the memories are stable over time?
It's in there.
Yes. No, it consolidates it. I mean, that's the point. What's memories are stable over time? It's like it's in there. Yes, yeah, no, it consolidates it.
I mean, that's the point.
What's the downside of Ambien?
Okay, here's the downside.
Okay, so people who take the drug say if you're going to Europe and you take it and then you
sleep really soundly, but often you find yourself in the hotel room and you completely have
no clue, you have no memory
of how you got there.
I've had that experience without Ambien or any other drugs where I am very badly jet
lagged and I wake up and for a few seconds, but what feels like eternity, I have no idea
where I am.
It's terrifying.
Well, that's another problem that you have with jet lag.
Jet lag really screws things up.
But this is something where it could be an hour.
You took the train or you took a taxi or something.
So here, now this seems crazy.
How could it be a way to improve learning and recall on one hand and then forgetfulness
on the other hand.
Well, it turns out what's important is
that when you take the drug, right,
in other words, it helps consolidate experiences
you've had in the past before you took the drug,
but it'll wipe out experiences you have in the future
after you take the drug, right?
Yeah, you steal it.
Sorry, I'm not laughing.
It must be a terrifying experience,
but I'm laughing because, you know,
there's some beautiful pharmacology
and indeed some wonderfully useful pharmaceuticals out there.
You know, some people may cringe to hear me say that,
but there are some very useful drugs out there
that save lives and help people deal with symptoms, et cetera.
Side effects are always a concern, but this particular drug profile, Ambien, that is,
it seems to reveal something perhaps even more important than the discussion about spindles
or Ambien or even sleep, which is that you got to pay the piper somehow, as they say.
That's right.
That you tweak one thing in the brain,
something else goes.
You don't get anything for free.
That's a true, I think that this is something
that is true not just of drugs for the brain,
but steroids for the body.
Sure.
Yeah.
I mean, steroids, even low dose testosterone therapy,
which is very popular nowadays,
will give people more vigor, et cetera,
but it is introducing a sort of second puberty.
And puberty is perhaps the most rapid phase of aging
in the entire lifespan.
Same thing with people who take growth hormone
would be probably a better example.
Because certainly those therapies
can be beneficial to people, but growth hormone gives people more vigor, but
it accelerates aging.
Look at the quality of skin that people have when they take growth hormone.
It looks more aged.
They physically change.
And I'm not for or against these things.
It's highly individual, but I completely agree with you.
I would also venture that with the growing interest in so-called nootropics
and people taking things like modafinil not just for narcolepsy, daytime sleepiness, but
also to enhance cognitive function. Okay, maybe they can get away with doing that every once
in a while for a deadline task or something, but my experience is that people who obsess
over the use of pharmacology to achieve certain brain states
pay in some other way.
Absolutely.
Whether or not stimulants or sedatives or sleep drugs and that behaviors will always
prevail.
Behaviors will always prevail as tools.
Yeah.
And one of the things about the way the body evolved is that it really has to balance a
lot of things.
And so with drugs, you're basically unbalancing it somehow.
And the consequence is, as you point out, is that in order to make one part better,
one part of your body, you sacrifice something else somewhere else.
As long as we're talking about brain states and connectivity across areas,
I want to ask a particular question.
Then I want to return to this issue about how best to learn,
especially in kids, but also in adulthood.
I've become very interested in and spent a lot of time
with the literature and some guests
on the topic of psychedelics.
Let's leave the discussion about LSD aside,
because do you know why there aren't many studies of LSD?
This is kind of a fun one.
No one is expected to know the answer.
Well, it's against the law, I think.
Oh, but there's, so is psilocybin or MDMA,
and there are lots of studies going on about this.
Yeah, it's changed.
But when I was growing up, you know,
as you know, it was against the law.
Right, so what I learned is that there are
far fewer clinical trials exploring the use of LSD
as a therapeutic, because with the exception
of Switzerland, none of the researchers are willing to stay in the laboratory as long
as it takes for the subject to get through an LSD journey, whereas psilocybin tends to
be a shorter experience.
Okay.
Let's talk about psilocybin for a moment.
My read of the data on psilocybin is that it's still open to question, but that some
of the clinical trials show pretty significant
recovery from major depression.
It's pretty impressive, but if we just set that aside and say, okay, more needs to be
worked out for safety, what is very clear from the brain imaging studies, the sort of
before and after resting state, task related, et cetera, is that you get more resting state
global connectivity, more areas talking to more areas
than was the case prior to the use of the psychedelic.
Given the similarity of the psychedelic journey, and here specifically talking about psilocybin
to things like rapid eye movement, sleep, and things of that sort, I have a very simple
question.
Do you think that there's any real benefit to increasing brain-wide connectivity?
To me, it seems a little bit haphazard, and yet the clinical data are promising, if nothing
else, promising.
And so is what we're seeking in life as we acquire new knowledge, as we learn tennis
or golf or take up singing or what have you, as we go from childhood into the late stages
of our life, that whole transition is what we're doing, increasing connectivity and communication
between different brain areas.
Is that what the human experience is really about?
Or is it that we're getting more modular?
We're getting more segregated in terms of this area, talking to this area in this particular
way? Feel free to explore area in this particular way.
Feel free to explore this in any way that feels meaningful or to say pass if it's not
a good question.
No, it's a great question.
You have all these great questions and we don't have complete answers yet.
But specifically with regard to connectivity, if you look at what happens in an infant's
brain during the first two years, there's a tremendous
amount of new synapses being formed.
This is your area, by the way.
You know about this and I do.
But then you prune them, right?
Second phase is that you overabundant synapses, and now what you want to do is to prune them.
Why would you want to do that?
Well, you know, synapses
are expensive. It takes a lot of energy to activate all of the neurons and the synapses
especially because there's the turnover of the neurotransmitter. And so what you want
to do is to reduce the amount of energy
and only use those synapses that have been proven
to be the most important, right?
Now, unfortunately, as you get older,
the pruning slows down, but doesn't go away.
So the cortex thins and so forth.
So I think it goes in the opposite direction.
I think that as you get older, you're losing connectivity.
But interestingly, you retain the old memories.
The old memories are really rock solid
because they were put in when you were young.
You had the foundation.
The foundation upon which everything else is built.
But it's not totally one way in the sense that even as an adult, as you know, you can
learn new things, maybe not as quickly.
By the way, this is one of the things that surprised me.
So Barbara and I have looked at the people who really were the benefit of the most.
It turns out that the peak of the demographic is 25 to 35.
Barbara.
Oakley, Oakley.
Yeah, she's really the mastermind.
She's a fabulous educator and background in engineering.
But what's going on?
So it turns out, we aimed our MOOC at kids in high school and college because that's
their business.
They go every day and they go into work.
They have to learn, right?
That's their business.
But in fact, very few of the students are actually, you know, they weren't taking the
course.
Why should they?
They spent all day in the class, right?
Why did they want to take another class?
So this is the learning to learn class.
Learning how to learn.
Okay, so you did this with Barbara.
So we did this, I did with Barbara,
and now 25 to 35, we have this huge peak, huge.
So what's going on?
Here's what's going on.
It's very interesting.
So you're 25, You've gone to college.
Half the people, by the way, who take the course went to college, right?
So it's not like filling in for college.
This is like topping it off.
But you're in the workforce.
You have to learn new skill.
Maybe you have mortgage.
Maybe you have children, right?
You can't afford to go off and take a course, or get another degree.
So you take a MOOC and you discover,
I'm not quite as agile as I used to be
in terms of learning, but it turns out with our course,
you can boost your learning.
And so that even though you're not as,
your brain isn't learning as quickly,
you can do it more efficiently.
This is amazing.
I want to take this course.
I will take this course.
What sort of time commitment is the course?
You already pointed out that it's zero cost,
which is amazing.
Yeah, okay, so it's bite-sized videos
lasting about 10 minutes each.
And there's about 50 or 60 over course of one month.
And are you tested? you self-test?
Yeah, yeah, there are tests, there are quizzes,
there are tests at the end,
and there are forums where you can go
and talk to other students, you have questions,
we have TAs.
No, it's-
And anyone can do this?
Anyone in the world.
In fact, we have people in India, housewives,
who say, thank you, thank you, thank you,
because I could have never learned about
how to be a better learner.
And I wish I had known this when I was going to school.
Why do more people not know about this learning to learn course?
Although, as people know, if I get really excited about it or about anything,
I'm never going to shut up about it.
But I'm going to take the course first because I want to understand the guts of it.
You'll enjoy it.
We have like 98% approval.
This is phenomenal.
It's sticky.
Is it math, vocabulary?
No, no math.
No vocabulary.
We're not teaching anything specific.
We're not trying to give you knowledge.
We're trying to tell you how to acquire knowledge
and how to do that, how to deal with exam anxiety,
for example, or how to, you know, we all procrastinate,
right, we put things off.
No, I'm kidding, we all procrastinate.
How to avoid that, we teach you how to avoid that.
Fantastic, okay, I'm gonna skip back a little bit now
with the intention of double clicking
on this learning to learn thing.
You pointed out that, in particular in California, with the intention of double clicking on this learning to learn thing.
You pointed out that in particular in California, but elsewhere as well, there isn't as much
procedural practice-based learning anymore.
I'm going to play devil's advocate here, and I'm going to point out that this is not what
I actually believe.
But when I was growing up, you had to do your times tables and your division
and then your fractions and your exponents,
and they build on one another.
And then at some point, you take courses
where you might need a graphing calculator.
To some people they can be like, what is this?
But the point being that there were a number of things
that you had to learn to implement functions
and you learn by doing, you learn by doing.
Likewise in physics class,
we were attaching things to strings
for macro mechanics and learning that stuff.
Okay, and learning from the chalkboard lectures.
I can see the value of both certainly.
And you explained that the brain needs both
to really understand knowledge
and how to implement and back and forth.
But nowadays, you know, you'll hear the argument,
well, why should somebody learn how to read a paper map
unless it's the only thing available
because you have Google Maps?
Or if they want to do a calculation,
they just put it into the top bar function on the internet
and boom, out comes the answer.
So there is a world where certain skills are no longer required.
And one could argue that the brain space and activity and time and energy in particular
could be devoted to learning new forms of knowledge that are going to be
more practical in the school and workforce going forward.
So how do we reconcile these things?
I mean, I'm of the belief that the brain is doing math, and you and I agree.
It's electrical signals and chemical signals, and it's doing math, and it's running algorithms.
I think you convinced us of that, certainly.
But how are we to discern what we need to learn
versus what we don't need to learn
in terms of building a brain that's capable of learning
the maximum number of things or even enough things
so that we can go into this very uncertain future?
Because as far as you know, and I know,
neither of us have a crystal ball.
So what is essential to learn?
And for those of us that didn't learn certain things
in our formal education,
what should we learn how to learn?
Well, this is generational.
Okay.
So, technologies provide us with tools.
You mentioned the calculator, right?
Well, a calculator didn't eliminate
the education you need to get in math,
but it made certain things easier.
It made it possible for you to do more things
and more accurately.
However, interestingly, students in my class often come up with answers that are off by
eight orders of magnitude.
That's a huge amount.
It's clear that they didn't key in the calculator properly, but they didn't recognize that it
was a very far, it was completely way off the beam because they didn't have a good feeling for the numbers.
They don't have a good sense of exactly how big it should have been, order of magnitude,
basic understanding.
The benefit is that you can do things faster, better, but then you also lose some of your
intuition if you don't have the procedural system in place.
I'm thinking about a kid that wants to be a musician
who uses AI to write a song about a bad breakup
that then is kind of recovered when they find new love.
And I'm guessing that you could do this today
and get a pretty good song out of AI,
but would you call that kid a songwriter or a musician?
On the face of it, yeah, the AI is helping.
And then you'd say, well, that's not the same
as sitting down with a guitar
and trying out different chords
and feeling the intonation in their voice.
But I'm guessing that for people
that were on the electric guitar,
they were criticizing people on the acoustic guitar.
So we have this generational thing where we look back and say, that's not the real guitar, they were criticizing people on the acoustic guitar. You know, so we have this generational thing
where we look back and say, that's not the real thing.
You need to get the, so what are the key fundamentals
is really a critical question.
Okay, so I'm gonna come back to that
because this is how, the way you put it at the beginning,
had to do with whether you're,
how your brain is allocating resources, okay?
So when you're younger, you can take in things.
Your brain is more malleable.
For example, how good are you on social media?
Well, I do all my own Instagram and Twitter
and those accounts have grown in proportion
to the amount of time I've been doing it.
So yeah, I would say pretty good.
I mean, I'm not the biggest account on social media,
but for a science health account, we're doing okay.
Thanks to the audience.
Well, this speaks well for the fact
that you've managed to break,
to go beyond the generation gap because-
I can type with my thumbs, Terry.
Okay, there you go.
That's a manual skill that you've learned.
That's a new phenomenon in human evolution.
I couldn't believe it. I saw people doing that, and now I can do it too.
But the thing is that if you learn how to do that early in life, you're much more good at it.
You can move your thumbs much more quickly.
Also, you can have many more tweets going,
and what are they called now?
They're not called tweets.
On X, I think they still call them tweets
because it's hard to verb the letter X.
Elon didn't think of that one.
I like X because it's cool, it's kind of punk,
and it's got a black kind of format,
and it fits with the engineer, like you know, and this kind of thing.
But yeah, we'll still call them tweets.
Okay, we'll call them tweets.
Okay, that's good.
But you know, I walk across campus and I see everybody, like half the people are tweeting
or you know, they're doing something with their cell phone.
I mean, it's unbelievable.
And you have beautiful sunsets at the Salk Institute.
We'll put a link to one of them.
I mean, it is truly spectacular, awe-inspiring
to see a sunset at the Salk Institute.
Every day is different.
And everyone's on their phones these days, sad.
And they're looking down at their phone
and they're walking along,
even people who are skateboarding, unbelievable.
I mean, it's amazing what the human being can do
when they get into something.
But what happens is the younger generation
picks up whatever technology it is
and the brain gets really good at it.
And you can pick it up later,
but you're not quite as agile,
not quite as maybe obsessive.
It fatigues me, I will point this out,
that doing anything on my phone feels fatiguing
in a way that reading a paper book
or even just writing on a laptop or a desktop computer
is fundamentally different.
I can do that for many hours.
If I'm on social media for more than a few minutes,
I can literally feel the energy draining out of my body.
Interesting.
I could do sprints or deadlifts for hours
and not feel the kind of fatigue
that I feel from doing
social media?
So, you know, this is fascinating.
I like to know what's going on in your brain.
Why is it?
And also, I'd like to know from younger people whether they have the same.
I think not.
I think my guess is that they don't feel fatigued because they got into this early enough. And this is actually a very, very,
I think that it has a lot to do with the foundation
you put into your brain.
In other words, things that you get,
you learn when you're really young are foundational
and they make things easier, some things easier.
Yeah, I spent a lot of time in my room as a kid, either playing with Legos or action
figures or building fish tanks or reading about fish.
I tended to read about things and then do a lot of procedural based activities.
I would read skateboard magazines and skateboard.
I was never one to really just watch a sport and not play it.
So bridging across these things.
So social media to me feels like an energy sink.
But of course I love the opportunity
to be able to teach to people
and learn from people at such scale.
But at an energetic level,
I feel like I don't have a foundation for it.
It's like I'm trying to like,
jerry-rig my cognition into doing something
that it wasn't designed to do.
Well, there you go.
And it's because you don't have the foundation.
You didn't do it when you were younger.
And now you have to sort of use the cognitive powers
to do a lot of what was being done now
in a younger person procedurally.
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My book, Chat GDP and the Future of AI, I went through and I looked at other people's experiences
with Chat GDP.
I just wanted to know what people were thinking.
I came across, it was an article, I think it was the New York Times,
of a technical writer who decided she would spend
one month using it to help her write things, her articles.
And she said that when she started out,
at the end of the day she was drained,
completely drained, and it was like working on a machine,
like a tractor or something, struggling, struggling, struggling to get it to work.
And then she started, said, well, wait a second, you know, what if I treat it like a human being?
What if I'm polite instead of, you know, being curt? So you said, suddenly, I started getting better answers by being polite and back and forth
the way you would with a human.
So saying, could you please give me information about so and so?
Yeah, please.
I'm really having trouble.
That answer you gave me was fabulous.
It was exactly what I was looking for.
Now I need you to go on to the next part
and help me with that too.
In other words, the way you talk to a human, right?
If you're an assistant.
Or is it that she was talking to the AI,
to chat GPT it sounds like in this case,
in the way that her brain was familiar
with asking questions to a human.
In other words, can that, so is the AI learning her
and therefore giving her the sorts of answers
that are more facile for her to integrate with?
I think it's both.
First of all, the chat GDP is mirroring
the way you treat it, it will mirror that back.
You treat it like a machine, it will treat you like a machine.
Okay, because that's what it's good at. But here's the surprise.
Surprise is, she said, once I started treating it
like a human, at the end of the day,
I wasn't fatigued anymore.
Why?
Well, it turns out that all your life,
you interact with humans in a certain way,
and your brain is wired to do that,
and it doesn't take any effort.
And so by treating the Chat GDP as if it were a human,
you're taking advantage of all the brain circuits
in your brain.
This is incredible.
And I'll tell you why, because I think many people,
not just me, but many people really enjoy social media,
learn from it.
I mean, yesterday I learned a few things that I thought were just fascinating about how
we perceive our own identity according to whether or not we're filtering it through
the responses of others or whether or not we take a couple of minutes and really just
sit and think about how we actually feel about ourselves.
Very interesting ideas about locus of self-perception and things like that.
I also looked at a really cool video of a baby raccoon popping bubbles
while standing on its hind limbs.
And that was really cool.
And social media could provide me both those things
within a series of minutes.
And I was thinking to myself, this is crazy, right?
The raccoon is kind of trivial,
but it delighted me and that's not trivial.
There you go, yes.
But here's the question.
Could it be that one of the detrimental aspects
of social media is that if we're complimenting one another
or if we are giving hearts or we're giving thumbs down
or we're in an argument with somebody
or we're doing a clap back or they're clapping back on us
or dunking, as it's called, on X,
that it isn't necessarily the way that we learned to argue.
It's not necessarily the way that we learn
to engage in healthy dispute.
And so as a consequence, it feels like,
and this is my experience,
that certain online interactions feel really good,
and others feel like they kind of grate on me,
because there's almost like an action step
that isn't allowed,
like you can't fully explain yourself
or understand the other person.
And I am somebody who believes in the power
of real face-to-face dialogue,
or at least on the phone dialogue.
And I feel the same way about text messaging.
I hate text messaging.
When text messaging first came out,
I remember thinking,
I was not a kid that passed notes in class.
This feels like passing notes in class.
In fact, this whole text messaging thing is beneath me.
That's how I felt.
And over the years, of course, I became a text messenger.
And it's very useful for certain things, be there in five minutes, running a few minutes
late in my case, that's a common one.
But I think this notion of what grates on us and as it relates to whether or not it matches
our childhood developed template of how our brain works
is really key because it touches on something
that I definitely wanna talk about today
that I know you've worked on quite a bit,
which is this concept of energy.
What we're talking about here is energy,
not woo biology, woo science wellness energy. We're talking about, we energy, not woo biology, woo science, wellness, energy.
We're talking about, we only have a finite amount of energy.
And years ago, the great Ben Barris sadly passed away, our former colleague and my postdoc
advisor came to me one day in the hallway and he stopped me and he said, he called me
Andy like you do.
And he said, Andy, how can we get such a rundown of energy
as we get older?
Why am I more tired today than I was 10 years ago?
I was like, I don't know, how are you sleeping?
He's like, I'm sleeping fine.
Ben never slept much in the first place,
but he had a ton of energy.
And I thought to myself, I don't know.
Like, what is this energy thing that we're talking about?
I want to make sure that we close the hatch
on this notion of a template neural system
that then you either find experiences invigorating or depleting.
I want to make sure we close the hatch on that, but I want to make sure that we relate
it at some point to this idea of energy.
Why is it that with each passing year of our life, we seem to have less of it?
You ask these great questions, and I wish that I had great answers.
Well, so far you really do have great answers.
They're certainly novel to me in the sense that I've not heard answers of this sort.
So there's a tremendous amount of learning for me today and I know for the audience.
But let's say somebody is 20 years old versus 50 years old versus what should they do?
I mean, we need to integrate with the modern world.
We also need to relate across generations.
Oh yeah, no, this is true.
People aren't retiring as much, they're living longer.
Birth rates are down,
but we have to get all get along as they say.
So, you know, it is interesting.
And I think it's true that we all, as we get older,
have less of the vigor,
if I can use a somewhat different word from energy.
We'll come back to that.
But I think there are some who manage to keep an act of life.
And here's something that, again, in our MOOC,
we really emphasize.
Could you explain a MOOC?
I think most people won't know what a MOOC is,
just for their sake.
Okay, this is, they've been around for about,
actually started at Stanford, Andrew Ng and Daphna Kohler.
So they have a company called Crosera.
And what happens is that you get professors,
and in fact, anybody who has knowledge
or professional expertise, to give lectures
that are available to anybody in the world
who have access to the internet.
And it could, this is like probably tens of thousands now.
Any specialty, history, science, music, you know, you name it.
There's somebody who's done, you know, who's an expert on that,
wants to tell you because they're excited about what they're doing. Okay, so what we wanted to do was to help people
with learning.
And so part of the problem is that it gets more difficult.
It takes more effort as you get older.
It depletes your vigor more if we're gonna stay
with this language of energy and vigor.
Yeah, that's right.
So let's actually use the word energy.
As you know, in the cell there is a physical power plant called the mitochondrion, which
is supplying us with ATP, which is the coin of the realm for the cell to be able to operate
all of its machinery, right?
And so one of the things that happens when you get older is that your mitochondrial run
down.
You have fewer of them and they're less efficient.
That's right.
They're less efficient.
And actually drugs can do that to you too.
They can harm mitochondria.
Recreational drugs.
No, the drugs you take for illness.
I'm not sure about recreational drugs, but I know that there are a lot of drugs that people take because they
have to.
But the other thing, and this is something, that's the bad news.
Here's the good news.
The good news is that you can replenish your energy by exercise.
Exercise is the best drug you could ever take. It's the cheapest drug you could ever take.
It's the cheapest drug you could ever take.
That can help every organ in your body.
It helps obviously your heart.
It helps your brain.
It rejuvenates your brain.
It helps your immune system.
Every single organ system in the body
benefits from a regular exercise.
I run on the beach every day at the Salk Institute.
And I also at the, it's on a mesa, 340 foot above the,
so I go down every day and then I climb up the cliff.
Yeah, those steps down to Black's Beach
are, they're a good workout.
They are, they are.
And so this is something that has kept me active,
and I went hiking in the Alps last fall.
So this is in September.
So this is, I think, something that people
really ought to realize is that it's like putting away
reserves of energy for when you get older,
the more you put away, the better off you are.
Here's something else.
Okay, now this is jumping now to Alzheimer's.
So a study that was done in China many, many years ago,
when I first came to La Jolla, San Diego,
I heard this from the head of the Alzheimer's program.
He had done a study in China on onset.
They went and they had three populations.
They had peasants who had almost no education.
Then they had another group that had high school education.
Then they were people who had advanced education.
So it turns out that the onset of Alzheimer's was earlier for the people who had no education.
And it was the latest for the people who had the most education.
Now this is interesting, isn't it?
And presumably the genes aren't that different, right?
I mean, they're all Chinese.
So one possibility, and obviously we don't really know why,
but one possibility is that the more you exercise
your brain with education,
the more reserve you have later in life.
I believe in the notion,
and I don't have a better word for it,
maybe you do, or a phrase for it,
is of kind of a cognitive velocity.
You know, I sometimes will play with this.
I'll read slowly or I'll see where my default pace of reading is at a given time of day,
and then I'll intentionally try and read a little bit faster while also trying to retain
the knowledge I'm reading.
Right.
Right.
So I'm not just reading the words.
I'm trying to absorb the information.
And you can feel the energetic demand of that.
And then I'll play with it, I'll kind of back off a little bit.
And then I'll go forward.
And I try and find the sweet spot where I'm not reading at the pace that is reflexive,
but just a little bit quicker while also trying to retain the information.
And I learned this when I had a lot of catching up to do at one phase of my
educational career. Fortunately, it was pretty early and I was able to catch up on most things,
you know, occasionally things slip through and I have to go back and learn how to learn, you know.
And if I get anything wrong on the internet, they sure as heck pointed out and then we go back and
learn. And guess what? I'd never forget that because punishment, social punishment is a great signal. So thank you all for keeping me learning.
But I picked that up from my experience
of trying to get good at things like skateboarding
or soccer when I was younger.
There's a certain thing that happens when skateboarding,
that was my sport growing up,
where it's actually easier to learn something going faster.
You know, most kids try and learn how to ollie
and kickflip standing in the living room on the carpet.
That's the worst way to learn how to do it.
It's all easier going a bit faster than you're comfortable.
It's also the case that if you're not paying attention,
you can get hurt.
It's also the case that if you pay too much
cognitive attention, you can't perform the
motor movements.
Right.
So there's this sweet spot that eventually I was able to translate into an understanding
of when I sit down to read a paper or a news article or even listen to a podcast, there's
a pace of the person's voice and then I'll adjust the rate of the audio where I have
to engage cognitively and I know I'm in a mode of retaining
the information and learning.
Whereas if I just go with my reflexive pace,
it's rare that I'm in that perfect zone.
So I point this out because perhaps
it will be useful to people.
I don't know if it's incorporated into your learning,
how to learn course, but I do think that there is something
which I call kind of cognitive velocity, which is ideal
for learning versus kind of leisurely scrolling.
And this is why I think that social media is detrimental.
I think that we train our brain basically to be slow, passive, and multi-context cycling
through and unless something is very high salience, it kind of makes us kind of fat
and lazy, forgive the language, but I'm kind of makes us kind of fat and lazy,
forgive the language, but I'm going to be blunt here,
fat and lazy cognitively,
unless we make it a point to also engage learning.
And my guess is it's tapping into this mitochondrial system.
Very likely, that's one part of it.
By the way, the way that you've adjusted the speed
is very interesting because it turns
out that stress, everybody thinks stress is bad, but no, it turns out stress that is transient,
that is only for a limited amount of time that you control is good for you, is good
for your brain, is good for your body.
I run intervals on the beach just the way that you do cognitive intervals when you're reading.
In other words, I run like hell for about 10 seconds,
and then I go to a jog and I run like hell
for another 10 seconds, and it's pushing your body
into that extra gear that helps the muscles,
the muscles need to know that,
this is what they've gotta put out,
and that's where you gain muscle mass,
not from just doing the same running pace every day.
Well, your intellectual and physical vigor is undeniable.
I've known you a long time.
You've always had a slight forward center of mass
in your intellect and even the speed at which you walk,
Terry, dare I say.
For a Californian, you're a quick walker.
Okay.
Yeah.
So that's a compliment, by the way.
East coasters know what I'm talking about and Californians would be like, you know,
why not slow down?
The reason to not slow down too much for too long is that these mitochondrial systems,
the energy of the brain and body,
as you point out, are very linked.
And I do think that below a certain threshold,
it makes it very hard to come back.
Just like below a certain threshold,
it's hard to exercise without getting very depleted
or even injured.
That we need to maintain this.
So perhaps now would be a good time to close the hatch
on this issue of how to teach young people,
everyone should take this learning to learn course
as a free resource, amazing.
As it relates to AI,
do you think that young people and older people now,
I'm 49, so I'll put myself in the older bracket,
should be learning how to use AI.
They are already learning how to use AI.
And again, it's just like new technology comes along,
who picks it up first?
It's the younger people.
And it's astonishing.
You know, they're using it a lot more than I am.
You know, I use it almost every day,
but I know a lot of students who basically... And by the way,
it's like any other tool, it's a tool.
You need to know how to use it.
Where do you suggest people start?
So I have started using Claude AI.
This was suggested to me by somebody expert in AI as an alternative to chat GPT.
I don't have anything against chat GPT, but I'll tell you, I really like the aesthetic
of Claude AI.
It's a bit of a softer beige aesthetic.
It feels kind of Apple-like.
I like the Apple brand.
It gives me answers.
Maybe it's the font, maybe it's the feel.
Maybe this goes back to the example you used earlier where I like Claude AI and I'm a big fan of it and they
don't pay me to say this.
I have never met them.
I have no relationship to them except that it gives me answers in a bullet pointed format
that feels very aesthetically easy to transfer that information into my brain or onto a page.
So I like Claude AI.
Use ChatG GPT.
How should people start to explore AI for sake of getting smarter, learning knowledge
just for the sake of knowledge, having fun with it?
What's the best way to do that?
Well, I think exactly what you did, which is there's now dozens and dozens of different
chat bots out there.
Different people will feel comfortable with one or the other.
Chat GDP is the first, so that's why it's kind of taken over a lot of the cognitive
space, right?
It's become like Kleenex, right?
That word.
That was why I used it as the first word in my book because it's iconic. But some of them, I have to say that, for example,
there are some that are really much better at math
than others.
Such as?
Google's Gemini recently did some fine tuning
with what's called chain of reasoning.
When you reason, you go through a chain of reasoning.
When you reason, you go through a sequence of steps.
And when you solve a math problem,
you go through a sequence of steps of doing,
fitting, first finding out what's missing
and then adding that.
And it went from 20% correct to 80, right?
On those problems.
And as people hear that, they probably think, well, that means 20% wrong still.
Could you imagine any human or panel of humans behind a wall where if you asked it a question
and then another question and another question, that it would give you back better than 80%
accurate information in a matter of seconds? So I think we are being perhaps a little bit unfair to compare these large language models
to the best humans rather than the average human, right?
As you said, most people couldn't pass the LSAT, the loss test to get into law school, or MCAT, the
test to get into medical school.
And CHAT GPT has.
Is there a world now where we take the existing AI, LLMs, these computers basically, that
can learn like a collection of human brains and send that somehow into
the future, right?
Give them an imagined future.
Okay.
Could we give them outcome A and outcome B and let them forage into future states that
we are not yet able to get to and then harness that knowledge and explore the two different
outcomes? and then harness that knowledge and explore the two different outcomes.
I think that's perhaps the better question in some sense,
because we can't travel back in time,
but we can perhaps travel into the future with AI
if you provide it different scenarios,
and you say, unlike a panel of people,
panel of people,
panel of experts, medical experts or space travel experts
or sea travel experts, you can't say,
hey, you know what, don't sleep tonight.
You're just gonna work for the next 48 hours.
In fact, you're gonna work for the next three weeks
or three months.
And you know what, you're not gonna do anything else.
You're not gonna pay attention to your health.
You're not going to do anything else.
But you can take a large language model
and you can say, just forage for knowledge
under the following different scenarios
and then have that fleet of large language models come back
and give us the information like, I don't know, tomorrow.
Okay, so I've lived through this myself.
Back in the 1980s, I was just starting my career, and I was one of the pioneers in developing
learning algorithms for neural network models.
Jeff Hinton and I collaborated together on something called the Bolson machine, and he
actually won a Nobel Prize for this recently.
Yeah, just this year.
Yeah, he's one of my best friends.
Brilliant, and he well deserved it for not just the Bolson machine,
but all the work he's done since then on machine learning
and then back propagation and so forth.
But back then, Jeff and I had this view of the future.
AI was dominated by symbol processing rules logic,
writing computer programs. For every problem logic, right? Writing computer programs.
For every problem you need a different computer program.
And it was very human resource intensive to write programs so that it was very,
very slow going.
And they never actually got there.
They never wrote a program for vision, for example,
even though the computer vision,
computer community really worked hard for a long time. But we had this view of the future. We had this view that nature has solved these problems,
and it is existence proof that you can solve the vision problem. Look,
every animal can see, even insects, right? Come on. Let's figure out how they did it. Maybe we can
help by following up on nature. Again, going back to algorithms, I was telling you.
And so in the case of the brain, what makes it different from a digital computer, digital
computers basically can run any program, but a fly brain, for example, only runs the program
that a special purpose hardware allows it to run.
Not much neuroplasticity.
There's enough there, just enough habituation and so forth so that you can survive.
And this is-
Survive 24 hours.
I'm not trying to be disparaging to the fly biologist,
but when I think of neuroplasticity,
I think of the magnificent neuroplasticity
of the human brain to customize to a world of experience.
I agree.
When I think about a fly,
I think about a really cool set of neural circuits
that work
really well to avoid getting swatted to eating and to reproducing, and not a whole lot else.
They don't really build technology.
They might have interesting relationships, but who knows, who cares?
It's not that it doesn't matter.
It's just a question of the lack of plasticity makes them kind of a meh species.
Okay, I can see I pressed your button here.
No, no, no, no, I love Fly Biology.
They taught us about algorithms for direction selectivity
and the visual system.
Oh, no, no, I love the Drosophila biology.
I just think that the lack of neuroplasticity
it reveals a certain key limitation.
And the reason we're the curators of the earth
is because we have so much plasticity.
Of course, of course.
But you have to, one step at a time,
nature first has to be able to create creatures
that can survive and then their brains get bigger
as the environment gets more complex and here we are.
But the key is that it turns out that certain algorithms
in the fly brain are present in our brain,
like conditioning, classical conditioning.
You can classical condition a fly in terms of training it
to when you give a reward, it will produce the same action.
This is like conditioned behavior.
And that algorithm that I told you about that isn't your value function, right?
Temporal difference learning.
That algorithm is in the fly brain.
It's in your brain.
So we can learn about learning from many species.
Okay.
I was just having a little fun poking at the fly biologists.
I actually think Trisophila has done a great deal as has honeybee biology. For instance, if you give caffeine to bees
on particular flowers, they'll actually try
and pollinate those flowers more
because they actually like the feeling of being caffeinated.
There's a bad pun about a buzz here,
but I'm not gonna make that fun
because everyone's done it before.
Right, right.
No, I fully absorb and agree with the value
of studying simpler organisms to find the algorithms.
Right. That's where we are right now. But now, just go into the future now. I'm telling
the story about what we really were. We were predicting the future. We were saying, this
is an alternative to traditional AI. We were not taken seriously. The was, experts said, no, no,
right programs, right programs.
They were getting all the resources, the grants, the jobs.
And we were just like the little furry mammals
under the feet of these dinosaurs, right, in retrospect.
I love the analogy.
But the dinosaurs died off.
This is, but the point I'm making is that
it's possible for our brain to make these extrapolations
into the future.
Why not AI versions of brains?
Why not?
I think your idea is a great one.
Yeah.
I mean, the reason I'm excited about AI, and increasingly so across the course of this conversation, is because there are very few
opportunities to forage information at such large scale and around the circadian clock.
I mean, if there's one thing that we are truly a slave to as humans is the circadian biology.
You got to sleep sooner or later.
And even if you don't, your cognition really waxes and wanes across the circadian cycle.
And if you don't, you're going to die early.
We know this.
Computers can work, work, work.
Sure, you got to power them.
There's the cooling thing.
There are a bunch of things related to that,
but that's tractable.
So computers can work, work, work.
And the idea that they can provide a portal into the future and that they can just bring
it back so we can take a look-see.
I'm not saying we have to implement their advice, but to be able to send a panel of
diverse, computationally diverse, experientially diverse AI experts into the future and bring us back a panel
of potential routes to take.
To me is so exciting.
Maybe a good example would be treatments for schizophrenia.
This is an area that I want to make sure that we talk about.
I grew up learning as a neuroscience student that schizophrenia was somehow a disruption
of the dopamine system because if you give neuroleptic drugs that block dopamine receptors
that you get some improvement in the motor symptoms and some of the hallucinations, et
cetera.
You now also have people who say, no, that's not really the basis of schizophrenia.
I'd love your thoughts.
And you have incredible work from people like Chris Palmer at Harvard, and we even have
a department at Stanford Now focusing, we even have people at Stanford Now focusing
on what Chris really founded as a field, which is metabolic psychiatry.
The idea that, who could imagine, I'm being sarcastic here, what you eat impacts your
mitochondria, how you exercise impacts your mitochondria, mitochondria impacts brain function.
And woe and behold,
metabolic health of the brain and body impacts schizophrenia symptoms.
He's looked at ways that people can use ketogenic diet, maybe not to cure, but to treat, and
in some cases, maybe even cure schizophrenia.
Here we are at this place where we still don't have a quote unquote cure for schizophrenia,
but you could send LLMs into the future and start to forage the most
likely all of the data in those fields.
Probably could do that in an hour.
Plus come up with a bunch of hypothesized different positive and negative result clinical
trials that don't even exist yet.
10,000 subjects in Scandinavia who go on ketogenic diet, who have a certain
level of susceptibility to schizophrenia based on what we know from twin studies, things
that never, ever, ever would be possible to do in an afternoon, maybe even in a year.
There's isn't funding, there isn't, and boom, get the answers back and let them present
us those answers.
And then you say, well, it's artificial, but so are human brains coming up with these experiments.
So to me, I'm starting to realize that it's not that we have to implement everything that
AI tells us or offers us, but it sure as hell gives us a great window into what might be
happening or is likely to happen.
Specifically for schizophrenia, I'm pretty sure that if we had these large language models
20 years ago, we would have known back then that ketamine would have been a really good
drug to try to help these people.
Tell us about the relationship between ketamine and schizophrenia.
Because I think a lot of people, and maybe you could define schizophrenia, even though
most people think about people hearing voices and psychosis, there's a bit more to it that maybe we just
bring out.
Okay.
So one of the things now that we know, see, the problem is that if you look at the endpoint,
that doesn't tell you what started the problem.
It started during early in development.
Schizophrenia is something that appears
when late adolescence, early adulthood,
but it actually is already a problem,
a genetic problem from the get-go.
So what is the concordance in identical twins?
Meaning if you have one identical twin,
if you have identical twins in the womb,
and one is destined to be full-blown schizophrenic.
What's the probability the other one will be?
Here's the experiment.
Okay, this has very, very,
been replicated many, many times, in mice, I should say.
Oh no, actually, okay, let me start with the human.
Okay, so ketamine is, for a long time,
and it still is a party drug, special K.
I've never taken it, but this is what I hear.
I don't know.
It's a dissociative anesthetic, right?
I'll tell you what happens,
because I've talked to these people who have done this.
You take ketamine, sub-anesthetic,
by the way, it's an anesthetic, it's given to children.
It's a pretty good anesthetic
and it's also used in veterinary medicine.
But in any case, you give it to,
you take young adults, here's what they experience. They experience out of body experience.
They have this wonderful feeling of energy.
And they're very, it's a high, but it's a very unusual high. Now, if they just go and have one experience, but if they have two, like they party two
days in a row, a lot of them come into the emergency room.
And here's what the symptoms are.
Full-blown psychosis, full-blown.
We're talking about indistinguishable
from a schizophrenic break.
So auditory hallucinations.
Yeah, auditory hallucinations, paranoia,
very, very advanced.
You'd say that, my God, this person here
has become a schizophrenic, and this is really,
like you say, the symptoms are the same. However, if you isolate them for a couple days, has become schizophrenic and this is really,
like you say, the symptoms are the same. However, if you isolate them for a couple days,
they'll come back, right?
So it means that schizophrenia can induce,
I'm sorry, ketamine can induce a form of schizophrenia,
psychosis, temporarily, not permanently, fortunately.
Okay, so what does it attack?
Okay, and there's another literature on this.
It turns out that it binds to a form of receptor,
a glutamate receptor called NMDA receptors,
which are very important by way for learning and memory.
But we know the target, and we also know
what the acute outcome is, that it reduces
the strength of the inhibitory circuit, the interneurons
that use inhibitory transmitters.
The enzyme that creates the inhibitory transmitter is downregulated.
And what does that do?
It means that there's more excitation.
And what does that mean when there's more excitation?
It means that there's more activity in the cortex and there's actually much more vigor and you start becoming crazy, right, if it's too much activity.
So this is interesting.
So this is telling us, I think, that we should be thinking about, and now there's a whole
field now in psychiatry that has to do with the glutamate hypothesis for the first, where the actual
imbalance first occurs.
It's an imbalance between the excitatory inhibitory systems that are in the cortex, keep you in
balance.
And NMDA and methyl deaspartate receptors are glutamate receptors.
Yes, they are.
They're one class. That's one class, that's right.
Okay, so now here is a hypothesis
for why ketamine might be good for depression.
People are taking it now who are depressed, right?
So here you have a drug that causes over-excitation,
and here you have a person who's under-excited.
Depression is associated with lower excitatory activity
in some parts of the cortex.
Well, if you titrate it, you can come back into balance.
Right?
So what you do is you fight depression with schizophrenia.
A touch of schizophrenia.
Now, you know, you have to keep giving, I think once every three weeks,
they have to have a new dose of ketamine,
but it's helped an enormous number of people
with very, very severe clinical depression.
So as we learn more about the mechanisms underlying
some of these disorders,
the better we are gonna be at extrapolating
and coming up with some solutions
at least to prevent it from getting worse.
By the way, I'm pretty sure that the large language models could have figured this out
long ago.
So, in an attempt to understand how we might be able to leverage these large language models
now, how would we have used these large language models long ago? Let's say you had 2024 AI technology in 1998, the year that I started graduate school.
At that time, the dopamine hypothesis, the schizophrenia was in every textbook.
There was a little bit about glutamate, perhaps, but it was all about dopamine.
So how would the large language models have discovered this?
Ketamine was known as a drug.
Ketamine by the way is very similar to PCP, phencycline, which also binds the NMDA receptor.
So how would-
Which is also a part of drug-
Which is also, yeah, not one I recommend, nor ketamine.
Frankly, I don't recommend any recreational drugs, but I'm not a recreational drug guy.
But what would those large language models do if they, so you've got 2024 technology
placed into 1998, they're forging for existing knowledge, but then are they able to make predictions?
Like, hey, this stuff is going to turn out to be wrong or hey, this stuff is-
Okay, okay.
You know, this is all very, very speculative and really we can begin actually to see this
happening now. So I have a colleague at the Salk Institute, Rusty Gage,
very distinguished neuroscientist,
and he discovered that there are new neurons
being born in the hippocampus, right,
which is something, in adults,
which is something that in a textbook
says that doesn't happen, right?
So that was around 1998 that Rusty did that.
That's right, and I actually have a paper with him
where we tested LTP, long-term potentiation,
actually the effects of exercise on neurogenesis.
Exercise increases neurogenesis.
It increases the cells, it increases neurogenesis
and also the cells that are active
are become part of the circuit.
More cells become integrated.
And this is true in humans as well, right?
Yeah.
And there was some cancer drug that was given that they showed that there were new cells
that they were able to later in post-mortem to actually see that they were born in the
adult.
Okay.
So here we are, OK, in 1998.
And the question is, can you jump?
Can you jump into the future?
OK.
So Rusty, we happened to talk about this issue,
about he's using these large language models now for
his research.
I said, oh, wow, how do you use it?
And he said, we use it as an idea pump.
What do you mean, idea pump?
Well, you know, we give it all of the experiments that we've done and we have, you know, the
literature, its access to the literature and so forth.
And we ask it for ideas for new experiments.
Oh, I love it.
I love it.
I was on a plane where I sat next to a guy
that works at Google.
And he's one of the main people there
in terms of voice to text and text to voice software.
And he showed me something.
I'll provide a link to it
because it's another one of these open resource things.
And I'm not super techie, I'm not like the,
I don't get an F in technology, I don't get an A plus.
I'm kind of in the middle.
So I think I'm pretty representative
of the average listener for this podcast, presumably.
What he showed me is that you can take,
you open up this website and you can take PDFs
or you take URLs, so websites, website
addresses, and you just place them in the margin.
You literally just drag and drop them there.
And then you can ask questions and the AI will generate answers that are based on the
content of whatever you put into this margin, those PDFs, those websites.
And the cool thing is it references them so you know which article it came from.
And then you can start asking it more sophisticated questions.
In the two examples of the effects of a drug, one being very strong and one being very weak. Which of these papers do you think is more rigorous
based on subject number,
but also kind of the strength of the findings?
Pretty vague things.
Strength of findings is pretty vague, right?
Anyone that argues those are weak findings,
those aren't enough subjects,
well, we know a hell of a lot about human memory
from one patient, HM.
So strength of findings when people is a subjective thing.
You really have to be an expert in a field to understand strength of findings and even
that.
And what's amazing is it starts giving back answers like, well, if you're concerned about
number of subjects, this paper, but that's a pretty obvious one, which one had more subjects,
but it can start critiquing these statistics
that they used in these papers in very sophisticated ways
and explain back to you why certain papers
may not be interesting and others are more interesting,
and it starts to weight the evidence.
Oh my God.
And then you say, well, with that weighted evidence,
can you hypothesize what would happen if, and so I've done a little
bit of this where it starts trying to predict the future based on 10 papers that you gave
it five minutes ago.
I don't think any professor could do that except in their very specific area of interest
and if they were already familiar with the papers and it would take them many hours if
not days to read all those papers in detail.
And they might not actually come up with the same answers,
right?
Right.
Yeah, so this is, actually this is something
that is happening in medicine, by the way,
for doctors who are using AIs and assistant.
This is really interesting.
So, and this is dermatology.
It was a paper in Nature.
Skin lesions, there's several, 2,000 skin lesions.
Some of them are cancerous and others are benign.
And so in any case, they tested the expert doctors and then they tested an AI and they
were both doing about 90%.
However, if you let the doctor use the AI,
it boosts the doctor to 98%.
98% accuracy.
Yes, and what's going on there?
It's very interesting.
So it turns out that although they got the same 90%,
they had different expertise.
That the AI had access to more data, and so it
could look at the lesions that were rare that the doctor may never have seen.
But the doctor has more in-depth knowledge of the most common ones that he's seen over
and over again, and knows the subtleties and so forth.
So putting them together, it makes so much sense that they're going to improve if they
work together. It makes so much sense that they're going to improve if they work together
And I think that now what you're saying is that using AI as a tool for discovery
it with
The expert who is interpreting and and and looking at the arguments the statistical arguments and also
Looking at the paper and maybe in a new way, maybe that's
the future of science.
Maybe that's what's going to happen.
Everybody's worried about, oh, AI is going to replace us.
It's going to be much better than we are, everything, and humans are obsolete.
Nothing can be further from the case.
Our strengths and weaknesses are different.
And by working together, it's going to strengthen,
it's both what we do and what AI does,
and it's going to be a partnership.
It's not going to be adversarial,
it's going to be a partnership.
Would you say that's the case for things like
understanding or discovering treatments
for a neurologic illness,
for discovering treatments for neurologic illness,
for avoiding large scale catastrophes,
like can it predict macro movements? Let me give an example.
Here in Los Angeles,
there's occasionally an accident on the freeway.
You have a lot of cameras over freeways nowadays.
You have cameras in cars.
You can imagine all of the data being sent in in real time
and you could probably predict accidents pretty easily.
I mean, these are just moving objects, right?
At a specific rate, who's driving haphazardly,
but you could also potentially signal takeover
of the brakes or the steering wheel of a car
and prevent accidents.
I mean, certain cars already do that,
but could you essentially eliminate,
well, let's do something even more important.
Let's eliminate traffic.
I don't know if you can do that,
because that's a funnel problem,
but could you predict physical events in the world
into the future?
Okay, this has already been done,
not for traffic, but for hurricanes.
So, you know, as you know,
the weather is extremely difficult to predict.
And except here in California,
where it's always gonna be sunny, right?
But now what they've done is to feed a lot of previous data from previous hurricanes
and also simulations of hurricanes.
You can simulate them in a supercomputer.
It takes days and weeks.
So it's not very useful for actually accurately predicting where it's going to hit Florida
But what they did was after training up the AI
On all of this data. It was able to predict with much better accuracy exactly where in Florida it's gonna
Make landfall and it it does that in on your laptop in ten minutes
And it does that on your laptop in 10 minutes.
Incredible. So something just clicked for me
and it's probably obvious to you and to most people,
but I think this is true.
I think what I'm about to say is true.
At the beginning of our conversation,
we were talking about the acquisition of knowledge
versus the implementation of knowledge.
Just learning facts versus learning
how to implement those facts in the form of physical action
or cognitive action, right?
Math problem is cognitive action, physical action.
Okay.
AI can do both knowledge acquisition.
It can learn facts, long lists of facts
and combinations of facts,
but presumably it can also run a lot of problem sets
and solve a lot of problem sets.
I don't think, except with some crude still to me examples of robotics, that it's very
good at action yet, but it will probably get there at some point.
Robots are getting better, but they're not doing what we're doing yet.
But it seems to me that as long as they can acquire knowledge and then solve different
problem sets, different iterations of combinations of knowledge, that basically they are in a
position to take any data about prior events or current events and make pretty darn good
predictions about the future and run those back to us quickly enough
and to themselves quickly enough
that they could play out the different iterations.
And so I'm thinking, you know, one of the problems
that seems to have really vexed neuroscientists
and the field of medicine and the general public
has been like the increase in the,
at least diagnosis of autism.
I've heard so many different hypotheses over the years.
I think we're still pretty much in the fog on this one.
Could AI start to come up with new and potential solutions and treatments if they're necessary,
but maybe get to the heart of this problem?
It might.
And it depends on the data you have,
it depends on the complexity of the disease,
but it will happen.
In other words, we will use those tools the best we can,
because obviously if you can make any progress at all
and jump into the future, wow, that would save lives.
That would help so many people out there.
I really think the promise here is so great
that even though there are flaws
and there are regulatory problems,
we really, really have to really push.
And we have to do that in a way that is going to help people
in terms of making their jobs better and helping them solve problems that
otherwise they would have had difficulty with and so forth.
It's beginning to happen, but these are early days.
We're at a stage right now with AI that is similar to what happened after the first flight
of the Wright brothers.
In other words.
It's that significant.
The achievement that the Wright brothers made
was to get off the ground 10 feet
and to power forward with a human being 100 feet.
That was it, that was the first flight.
And it took an enormous amount of improvements. The most difficult thing that had to be That was it. That was the first flight. And it took an enormous amount of
improvements. The most difficult thing that had to be solved was control. How do you control
it? How do you make it go in the direction you want it to go? And shades of what's happening
now in AI is that, you know, we are off the ground. We were not going very far yet, but
who knows where it will take us into the future.
Let's talk about Parkinson's disease, a depletion of dopamine neurons that leads to difficulty
in smooth movement generation and also some cognitive and mood-based dysfunction.
Tell us about your work on Parkinson's and what did you learn?
As you point out, Parkinson's is first a degenerative disease. It's very interesting because the
dopamine cells are a particular part of the brain, the brain stem, and they are the ones
that are responsible for procedural learning. I told you before about temporal difference.
It's dopamine cells.
And it's a very powerful way for the, it's a global signal,
it's called a neuromodulator, because it modulates all the other signals
taking place throughout the cortex.
And also, it's very important for learning
And also, it's very important for learning sequences of actions that produce survival for survival.
But the problem is that with certain environmental insults, especially toxins like pesticides, those neurons are very vulnerable.
And when they die, you get all of the symptoms that you just described.
The people who have lost those cells actually before the treatment, L-Dopa, which is a dopamine
precursor,
they actually became comatose, right?
They didn't move.
They were still alive, but they just didn't move at all.
You know, they-
It's tragic.
Yeah, it's locked in, it's called.
Yeah, it's tragic, tragic.
So when the first trials of L-DOPA were given to them,
it was magical because suddenly they started talking again.
So, I mean, this is amazing, amazing.
I'm curious, when they started talking again,
did they report that their brain state
during the locked-in phase was slow velocity?
Like, was it sort of like a dreamlike state
or they felt like they were in a nap or were they in there like screaming to get out?
Because their physical velocity obviously was zero.
They're locked in after all.
And I've long wondered when coming back from a run or from waking up from a great night's
sleep when I shift into my waking state, whether or not physical velocity and
cognitive velocity are linked.
Okay.
That's a wonderful observation or a question.
You know the answer.
Okay.
Here's something that is really amazing.
It was discovered interestingly when they tend to move slowly, as you said, but to them, cognitively, they think they're moving fast.
Now it's not because they can't move fast, because you can say, well, can you move faster?
Sure.
And they move normal.
But to them, they think they're moving at super velocities.
So it's a set point issue.
So it's a set point issue.
Yes, it's all about set points.
That's what's really going on. And as the set point gets further and further down, you know, that now without moving at all,
they think they're moving, right? I mean, this is what's going on. By the way, you can ask them,
you know, what was it like? You know, we were talking to you and you didn't respond. Oh,
I didn't feel like it. The brain confabulates an answer. They have, well, they, that they confabulated it
because they didn't have enough energy
or they couldn't initiate, they couldn't initiate actions.
That's one of the things that they have trouble with,
with movements, you know, starting a movement.
Yeah, as you can tell, I'm fascinated by this notion
of cognitive velocity.
And again, there may be a better or more accurate
or official language for it,
but I feel like it encompasses so much
of what we try to do when we learn.
And the fact that during sleep,
you have these very vivid dreams
during rapid eye movement sleep.
So cognitive velocity is very fast.
Time perception is different
than in slow wave sleep dreams.
And I really think there's something to it
as at least one metric that relates to brain state.
I've long thought that we know so much more
about brain states during sleep
than we do about wakeful brain states.
That we talk about focus, motivated, flow.
I mean, these are not scientific terms.
I'm not being disparaging of them.
They're pretty much all we've got
until we come up with something better. But I think we're biologists and neuroscientists scientific terms. I'm not, I'm not being disparaging of them. They're pretty much all we've got
until we come up with something better. But like we're biologists and neuroscientists
and computational neuroscientists in your case. And we're like trying to figure out
like, like what brain state are we in right now? Our cognitive velocity is, is a, you
know, a certain value. But I think the more that people think about this, you know, I'll
venture to say that the more that they think
a little bit about their cognitive velocity
at different times of day, start to notice
that there's a, tends to be a few times of day.
For me, it tends to be early to late mid morning.
And then again, in the evening,
after a little bit of trough and energy,
that boy, that hour and a half each,
like that's the time to get real work done.
I have the same experience.
I can mentally sprint far at those times.
Right.
But there are other times of day when
I don't care how much caffeine I drink.
I don't care, unless it's a stressful event
that I need to meet the demands of that stress,
I just can't get to that faster pace
while I'm also engaging.
You can read faster, you can listen, but you're not using the information.
You're not storing the information.
What times a day for you are-
No, I get most done in the morning.
And then later after dinner is also different though.
I think in the morning I'm better at creative stuff
and then I think that in the evening
I'm better at actually just cranking it out.
Interesting.
Given the relationship between body temperature
and circadian rhythm, I would like to run an experiment
that relates core body temperature to cognitive
velocity.
I've actually noticed this is something that is just purely subjective, but the temperature
of the salt inside the building is kept 75.
It's like, you know, it's rock solid.
But in the afternoon, I feel a little chilly. It's probably my internal.
Sure.
Body temperature starts to come down.
Yeah, it's probably going down.
And that may correspond to the loss of energy,
the ability for the brain and everything else.
By the way, you know this is Q10, this is a jargon.
Every single enzyme in your, every cell
can go at different rates depending on the temperature,
right?
And so, yeah, so the body temperature is doing this
and all the cells are doing this too, right?
So this is, it's an explanation.
I'm not sure if it's the right one, but.
Yeah, Craig Heller, my colleague at Stanford
in the biology department has beautifully described
how the enzymatic control over pyruvate, I believe it is, controls muscular failure.
That local muscular failure, when people are trying to move some resistance, has everything
to do with the temperature, the local temperature that shuts down certain enzymatic processes
that don't allow the muscles to contract the
same way.
He knows the details and he covered them on this podcast.
I'm forgetting the details.
You can start to go, wow, these enzymes are so beautifully controlled by temperature.
Of course, his laboratory is focused on ways to bypass those temperature or to change temperature
locally in order to bypass those limitations and have shown them again and again.
It's just incredible.
Yeah, I hear we're speculating about what it would mean for cognitive velocity, but
I think it's such a different world to think about the underlying biology as opposed to
just thinking about like a drug.
You know, you increase dopamine and norepinephrine and epinephrine, the so-called catecholamines,
and you're going to increase energy focus and alertness,
but you're gonna pay the price.
You're gonna have a trough in energy focus and alertness
that's proportional to how much greater it was
when you took the drug.
Boy, amphetamines are a good example.
Boy, you're going a mile a minute
when you're taking the drug.
Of course, I fully understand that that's your impression.
The reality is you don't actually accomplish that much more.
Have any LLMs, so AI, been used to answer this really pressing question of what is going
to be the consequence on cognition for these young brains that have been weaned while taking
Ritalin, Adderall, Vyvanse, and other stimulants because we have millions
of kids that have been raised this way.
We've done this experiment on our whole cadre, a whole generation.
I really would like to know the answer.
I wonder if anybody's studying it.
That's really a great question because we gave them speed effectively, the drug that
causes the brain to be activated.
But by the way, you know, the consequence is that, you know, when it wears off, you
have no energy, right?
You're just completely spent.
That's it.
That's the pit.
That's the pit.
And so, but that's why you take more of it, you see.
That's the problem is it's the pit. And so, but that's why you take more of it. You see, that's the problem is it's a spiral.
I love how today you're making it so very clear
how computation, how math and computers and AI now
are really shaping the way that we think
about these biological problems,
which are also psychological problems,
which are also daily challenges.
I also love that we touched on mitochondria
and how to replenish mitochondria.
I want to make sure that we talk about a couple of things
that I know are in the back of people's minds,
no pun intended here,
which are consciousness and free will.
Normally, I don't like to talk about these things,
not because they're sensitive,
but because I find the discussions around them typically to be more philosophical than neurobiological, and they
tend to be pretty circular.
And so you get people like Kevin Mitchell, who I think has a book about free will, he
believes in free will.
You've got people like Robert Sapolsky, wrote the book Determined, he doesn't believe in
free will.
How do you feel in free will.
How do you feel about free will?
And is it even a discussion that we should be having?
Well, if you go back 500 years, you know, to the Middle Ages,
the concept didn't exist,
or at least not in the way we use it.
Because everybody, it was the way that we,
that humans felt about the world and how it worked and
its impact on them was that it's all fate. They had this concept of fate, which is that
there's nothing you can do, that something is going to happen to you because of what's going on in the gods up above,
or whatever it is, right?
You attribute it to the physical forces around you
that caused it, not to your own free will,
not to something that caused this to happen to you, right?
So I think that these words, by the way, that we use,
free will, consciousness, intelligence,
understanding, they're weasel words because you can't pin them down.
There is no definition of consciousness that everybody agrees on.
It's tough to solve a problem, a scientific problem, if you don't have a definition that
you can agree on.
And, you know, there's this big controversy about whether these large language models
understand language or not, right?
The way we do.
And what it really is revealing is we don't understand what understanding is.
Literally, we don't have a really good argument
or measure that you could measure someone's understanding
and then apply it to the GDP and see whether it's the same.
It probably isn't exactly the same,
but maybe there's some continuum here
we're talking about, right?
The way I look at it,
it's as if an alien suddenly landed on Earth and started talking to us in English, right?
And the only thing we can be sure of was that it's not human.
I met some people that I wondered about their terrestrial origins.
Okay, okay.
Well, okay, now there's a big diversity amongst humans too.
You're right about that.
Yeah, yeah, yeah.
Certain colleagues of ours at UCSD years ago, one in particular in the physics department
who I absolutely adore as a human being, just had such an unusual pattern of speech, of
behavior, totally appropriate behavior, but just unusual.
In the middle of a faculty meeting,
we just kind of turned to me and started talking
while the other person was presenting.
And I was like, maybe not now.
And he would say, oh, okay.
But in any other domain,
you'd say he was very socially adept.
And so, you know, there's certain people
that just kind of discard with convention,
and you kind of want to like, is he an alien?
It's kind of cool, you know, in a cool way.
Like, you know, he's one of my, again,
a friend and somebody I really delight in.
It's true, it's true.
You know, no, no, not everybody has adopted
the same social conventions.
You know, it could be a touch of autism.
Mm-hmm, yeah.
That's a problem.
I mean, in other words,
there are very high functioning autistic people out there.
He's brilliant.
And often they are, you know,
there are high people who are brilliant with autism.
But, you know.
Could you build an LLM that was more
on one end of the spectrum versus the other
to see what kind of information they forage for?
I reviewed a paper.
It seemed like it would be a really important thing to do.
It's been done, okay.
There was a paper that I reviewed
where they took the LM and they fine-tuned it
with different data from people with different disorders,
you know, autism and so forth.
And sociopaths, you know, the autism and so forth. And sociopaths, you know.
That's scary.
But you'd want to know the answer.
No, no, and they got these LLMs to behave
just like those people who have these disorders.
You can get them to behave that way, yes.
Could you do political leaning and values? I haven't seen that, but it's pretty clear that to me, at least that if you can do sociopathy,
you can probably do any political belief.
But you could also view all this as, you could take benevolent tracks. hyper creative, sensitive to emotional tone of voices and find out what kind of information
that person brings, excuse me, that LLM brings back versus somebody who is very oriented
towards just the content of people's words as opposed to what, you know, because among
people you find this.
You know, if you've ever left a party with a significant other,
and sometimes someone will say,
I've had this experience with like,
did you see that interaction between so-and-so?
I'm like, no, what are you talking about?
Like, did you hear that?
I'm like, no, not at all.
I didn't hear, I heard the words,
but I did not pick up on what you were picking up on.
And it was clear that there's two very different experiences
of the same content,
based purely on a difference in interpretation of the tonality.
Okay, there's a lot of information that, as you point out, which has to do with the tone,
the spatial expressions, you know, there's a tremendous amount of information that is
passed not just with words, but with all the other parts, the
visual input and so forth.
And some people are good at picking that up and others are not.
There's a tremendous variability between individuals.
And you know, that's what biology is all about, diversity.
And it's all about needing gene pool that's very diverse so that you can evolve and survive catastrophic changes that occur
in a climate, for example.
But wouldn't it be wonderful if we could create an LLM that could understand
what those differences are.
Now just think about it, right?
That could truly diverse LLM
that integrated all those differences.
Yeah, but here's what you'd have to do.
What you'd have to do is to train it up on data
from a bunch of individuals, human individuals.
Now one of the things about these LLMs
is that they don't have a single persona.
They can adopt any persona.
You have to tell it what you're expecting from.
Or ask it in a way that works for you
and you'll get back a certain persona.
If you, if you, if, I once gave it an abstract
from a paper, very technical, a computational paper.
And I said, you are a neuroscientist.
I want you to explain this abstract to a 10-year-old.
It did it in a way that I could never have done it.
It really simplified it.
Some of the subtleties were not in it,
but it explained what plasticity it was
and explained what a synapse is.
And it did that. It's almost like a qualifying exam for a graduate student.
I saw something today on X, formerly known as Twitter, that blew my mind that I wanted
your thoughts on that is very appropriate to what you're saying right now, which is
someone was asking questions of an LLM on chat GPT or maybe one of these other anthropic
or Claude or something like that.
Probably misused those names.
One of the AI online sites,
and somewhere in the middle of its answers,
the LLM decided to just take a break
and start looking at pictures of landscapes in Yosemite.
Like the LLM was doing what a maybe cognitively fatigued
person or what any kind of online person online would do,
which was to like take a break
and look at a couple of pictures of something,
maybe they're thinking about going camping there
or something and then get back to whatever task.
We hear about hallucinations in AI,
that it can imagine things that aren't there, just
like a human brain, but that blew my mind.
I haven't encountered that, but it's fascinating.
That's a sign of a real generative internal model. If it's, see, here's the thing that,
the thing that most distinguishes, I think, in LLM from human is that, you know, if you,
if you go into a room, quiet room,
and just sit there without any sensory stimulation,
your brain keeps thinking, right?
In other words, you think about what you wanna do,
you know, planning ahead about what you want to do,
planning ahead or something that happened to you
during the day, right?
Your brain is always generating internally.
After talking to you,
one of these large language models just goes blank.
There is no self continuous, self-generated thoughts.
And yet we know self-generated thoughts.
And yet we know self-generated thought and in particular brain activity during sleep,
as you illustrate earlier with the example
of sleep spindles and rapid eye movement,
sleep are absolutely critical for shaping the knowledge
that we experienced during the day.
So these LLMs are not quite where we are at yet.
I mean, they can outperform us in certain things like go,
but how soon will we have LLMs, AI that is,
with self-generated internal activity?
We're getting closer.
And so this is something I'm working on myself actually, self-generated internal activity. We're getting closer.
And so this is something I'm working on myself, actually,
trying to understand how that's done in our own brains,
was generating continual brain activity that leads to planning and things.
We don't know what the answer to that is yet in neuroscience.
And by the way, you go to a lecture and you hear the words one after the next over an hour,
and you see the slides one after the next.
At the end, you ask a question.
Let's think about what you just did.
Somehow, you're able to integrate all that information over the hour and then use your long-term memory then to come up with some insight or some issue that you want. How did your
brain remember all that information, working memory, traditional working
memory that neuroscientists study is only if you're a few seconds like maybe a
telephone number or something. But we're talking about long-term working memory.
We don't understand how that is done.
And LLMs, actually large language models, can do something.
It's called in-context learning.
And it was a great surprise because there is no plasticity.
The thing learns at the beginning.
You train it up on data, and then all it does after that is to inference, you know, fast
loop of activity, one word after the next, right?
That's what happens with no learning, no learning.
But it's been noticed that as you continue your dialogue, it seems to get better at things.
How could that be?
How could it be in context learning,
even though there's no plasticity?
That's a mystery.
We don't know the answer to that question yet,
but we also don't know what the answer is
for humans either.
Right.
Could I ask you a few questions about you
and as it relates to science and your trajectory,
building off of what you were just saying, do you have a practice of meditation or eyes closed,
sensory input reduced or shut down to drive your thinking in a particular way? Or are you,
you know, at your computer talking to your students and postdocs and
sprinting on the beach?
Or asleep?
No, it's funny you mention that because I get my best ideas, not sprinting on the beach,
but just either walking or jogging.
And it's wonderful.
I don't know.
I think as serotonin goes up, it's another neuromodulator.
I think that that stimulates ideas and thoughts.
And so inevitably I come back to my office
and I can't remember any of those great ideas.
What do you do about that?
Well, now I take notes.
Okay, voice memos?
Yeah.
And some of them pan out.
There's no doubt about it.
Sure.
That you're put into a situation,
it is a form of meditation.
You know, if you're running in a steady pace,
nothing distracting about, you know, the beach.
Or do you listen to music or podcasts or?
No, I never listen to anything except my own thoughts.
So there's a former guest on this podcast who, she happens to be triple-degree from
Harvard, but she's more in the kind of like personal coach space, but very, very high
level and impressive mind, impressive human all around.
And she has this concept of wordlessness that can be used to accomplish a number of different
things, but this idea that allowing oneself
or creating conditions for oneself
to enter states throughout the day,
or maybe once a day, of very minimal sensory input.
No lecture, no podcast, no book, no music, nothing.
And allowing the brain to just kind of idle
and go a little bit non nonlinear, if you will.
Right.
Where we're not constructing thoughts
or paying attention to anyone else's thoughts
through those media venues in any kind of structured way
as a source of great ideas and creativity.
It's been studied.
Psychologists call it mind wandering.
Mind wandering.
Yeah, it is a significant literature.
And it's often when you have an aha moment, right?
You know, your mind is wandering and it's thinking nonlinearly in the sense of not following
a sequence that is logical, you know, hopping from thing to thing.
Often that's when you get a great idea, just letting your mind wander. Yeah, and from thing to thing. Often that's when you get a great idea,
with just letting your mind wander.
Yeah, and that happens to me.
I wonder whether social media and just texting
and phones in general have eliminated a lot of the,
you know, walks to the car after work
where one would normally not be on a call
or in communication with anyone or anything.
I used to do experiments where I was, you know,
like pipetting and running, you know,
amino histochemistry and it was very relaxing.
And I could think while I was doing,
cause I knew the procedures and then, you know,
you had to pay attention to certain things,
write them down, but I would often feel like,
wow, I'm both working and relaxing and thinking of things.
And then I would listen to music sometimes.
Okay, so we have a whole session, a clip,
in learning how to learn about exactly this phenomenon.
Here's what we tell our students, right?
Is that, you know, if you're having trouble
with some concept or you don't understand something,
you're beating your head against the wall,
don't, stop, stop.
Just go off and do something.
Go off and clean the dishes.
Go off and walk around the block.
And inevitably what happens is when you come back,
your mind is clear and you figure out what to do.
And that's one of the best pieces of advice
that anybody could get because, you know,
we don't, nobody has told us how the brain works, right?
Some people are really good at intuitings because they've experienced maybe, but everybody,
okay, the other thing is everybody I know who's really made important contributions.
And I'll bet you're one of them.
You know, you're struggling with some problem at night,
and you go to bed, and you wake up in the morning, ah.
That's the solution.
That's what I should do.
First thing in the morning when I wake up
is when I'm almost bombarded with, I wouldn't say insight and not always meaningful insight,
but certainly what was unclear
becomes immediately clear on waking.
That's right.
That's the thing that is so amazing about sleep.
And you can see people who know this can count on it.
In other words, the key is to think about it
before you go to sleep.
Right? Your brain works on it during the other words, the key is to think about it before you go to sleep.
Your brain works on it during the sleep period.
So don't watch TV because then who knows what your brain's going to work on.
Use the time before you fall asleep to think about something that is bothering you or maybe
something that you're trying to understand, maybe a paper that you read the paper and say,
oh, I'm tired, I'm gonna go to sleep.
You wake up in the morning and say,
oh, I know what's going on in that paper.
Yeah, I mean, that's what happens.
You can use, once you know something
about how the brain works, you can take advantage of that.
Do you pay attention to your dreams?
Do you record them?
No, no, okay.
So here's the problem.
Dreams seem so iconic
and a lot of people somehow attribute things to them
but there has never been any good theory
or any good understanding,
first of all, why we dream.
It's still not completely clear.
I mean, there are some ideas.
Or why this particular dream?
Does that have some significance for you?
And the only thing that I know that might explain a little bit is that the dreams are often very visual, rapid eye movement sleep
so that there's something happening that actually is interesting.
All the neuromodulators are downregulated during sleep and then during REM sleep, acetylcholine
comes up.
So that's a very powerful neuromodulator.
It's important for attention, for example.
But it doesn't come up in the prefrontal cortex, which means
that the circuits in the prefrontal cortex that are interpreting the sensory input coming
in are not turned on.
So any of these, whatever happens in your visual cortex is not being monitored anymore.
So you get bizarre things, you know, that you start floating and, you know, things happen
to you and, you know, it's not anchored anymore.
So that still doesn't explain why, right?
Why you have that period.
It's important because if you block it and there are some sleeping pills that do block
it, you know, it really does cause problems with, you know, normal cognitive function. Cannabis as well.
People who come off cannabis
experience a tremendous REM rebound
and lots of dreaming in the days and weeks
and months after cannabis.
Wow.
I don't wanna call it withdrawal
because that has a different meaning.
No, no, it's a, it's an imbalance that was caused of,
but you know, because the brain adjusted to the,
you know, the endocannabinoid levels.
And now it's got to go back and it takes time,
but it's interesting, isn't interesting, it affects dreams.
I think that may be a clue.
Yeah, very, very common phenomenon.
I'm told, I'm not a cannabis user,
but no judgment there, I just am not. It's
actually a book I read years ago when I was in college, so a long time ago, by Alan Hobson,
who was out at Harvard.
Oh yeah, I know him.
Oh, cool. So I never met him, but he had this interesting idea that dreams, in particular rapid eye movement dreams,
were so very similar to the experience that one has
on certain psychedelics, LSD,
Lycidic Acid, Diethylmolide, or psilocybin.
And that perhaps dreams are revealing the unconscious mind,
you know, and not saying this in any psychological terms,
you know, that, you know, when we're asleep,
our conscious mind can't control thought and action in the
same way, obviously, and kind of it's sort of a recession of the water line, you know,
so we're getting more of the unconscious processing revealed.
You know, that's an interesting hypothesis.
How would you test it?
I'd probably have to put someone in a scanner, have them go to sleep,
put them in the scanner on a psilocybin journey.
This kind of thing.
You know, it's tough.
I mean, any of these observational studies,
of course we both know, are deficient in the sense
that what you'd really like to do
is control the neural activity.
You'd like to get in there and tickle the neurons over here
and see how the brain changes.
And you'd love to get real-time subjective report.
This is the problem with sleep and dreaming is people,
you can wake people up and ask them
what they were just dreaming about,
but you can't really know what they're dreaming about
in real time.
It's true. Yeah, it's true.
By the way, you know, there are two kinds of dreams.
Very interesting.
So if you wake someone up during REM sleep,
you get very vivid changing.
Dreams are always different and changing.
But if you wake someone up during slow wave sleep,
you often get a dream report,
but it's a kind of dream that keeps repeating
over and over again every night.
And it's a very heavy emotional content.
Interesting, that's in slow wave sleep. Yeah.
Because I've had a few dreams over and over and over
throughout my life.
So this would be in slow wave sleep.
Yeah, probably slow wave sleep, yeah.
Fascinating.
As a neuroscientist who's computationally oriented,
but really you incorporate the biology so well
into your work.
So that's one of the reasons you're you,
you're this luminary of your field, and who's also now really excited about AI. What are you most excited
about now? Like if you had, and you know, of course this isn't the case, but if you had
like 24 more months to just pour yourself into something and then you had to hand the keys to your lab over to someone else, what would you go all in on?
Well, so the NIH has something called the Pioneer Award.
And what they're looking for are big ideas
that could have a huge impact, right?
So I put one in recently and here's the title is
I put one in recently, and here's the title,
is a temporal context in brains and transformers.
And in brains and transforms? Transformers.
Formers.
AI, right.
The key to ChatGDP is the fact that it's new architecture,
it's a deep learning architecture, feed forward network,
but it's called a transformer.
And it has certain parts in it that are unique.
There's one called self-attention.
And it's a way of doing what is called temporal context.
What it does is it connects words that are far apart.
You give it a sequence of words
and it can tell you the association.
Like if I use the word this,
and then you have to figure out in the last sentence,
what did it refer to?
Well, there's three or four nouns it could have referred to,
but from context, you can figure out which one it does,
and you can learn that association.
Could I just play with another example
to make sure I understand this correctly?
I've seen these word bubble charts.
Like if we were to say piano, you'd say keys,
you'd say music, you'd say seat,
and then it kind of builds out a word cloud association.
And then over here we'd say,
I don't know, I'm thinking about the Salkins,
do I say sunset, Stonehenge, anyone that looks up,
there's this phenomenon, Salkhenge.
This kind of-
Then you start building out a word cloud over there.
These are disparate things,
except I've been to a classical music concert
at the Salk Institute.
The Symphony of Salk. Twice.
So they're not completely non-overlapping.
And so you start getting associations at a distance
and eventually they bridge together.
Is this what you're referring to?
Yes.
I think that that's an example,
but it turns out that every word is ambiguous
and has like three, four meetings.
And so you have to figure that out from context.
And so in other words, there are words that live together
and that come up often.
And you can learn that from just by predicting
the next word in a sentence.
That's how a transformer is trained.
You give it a bunch of words and it keeps predicting the next word in a sentence. That's how a transformer is trained.
You give it a bunch of words
and it keeps predicting the next word in a sentence.
Like in my email now, it tries to predict the next word.
Exactly.
And it's mostly right part of the time.
Okay, well, that's because it's a very primitive version
of this algorithm.
What happened is if you train it up on enough,
not only can it answer the next word, it internally builds
up a semantic representation in the same way you describe the words that are related to
each other, having associations.
It can figure that out, and it has representations inside this very large network with trillions
of parameters.
It's unbelievable how big they were gotten.
And those associations now form an internal model
of the meaning of the sentence.
Literally, this is something that now
we've probed these transformers,
and so we pretty much are pretty
confident.
And that means that it's forming an internal model of the outside world, in this case a
bunch of words.
And that's how it's able to actually respond to you in a way that is sensible, that makes
sense and actually is interesting, and so forth.
And it's all for the self-attention I'm talking about.
So in any case, my pioneer proposal
is to figure out how does the brain do self-attention.
Right?
It's gotta do it somehow.
And I'll give you a little hint.
Basal ganglia.
It's in the basal ganglia.
That's my hypothesis.
Well, we'll see.
I mean, I'll be working with experimental people.
I've worked with John Reynolds, for example,
who studies primate visual cortex,
and we've looked at traveling waves there,
and there are other people that have looked at in primates.
And so now these traveling waves, I think,
are also a part of the puzzle, pieces of the puzzle
that are gonna give us a much better view
of how the cortex is organized
and how it interacts with the basal ganglia.
We've already been there, but we're still,
neuroscientists have studied each one of these parts
of the brain independently, and now we have to start
thinking about putting the pieces of the puzzle together,
trying to get all the things that we know about these areas
and see how they work together in a computational way.
And that's really where I want to go.
I love it, and I do hope they decide where I want to go. I love it.
And I do hope they decide to fund your pioneer award.
I do too.
Yeah.
And should they make the bad decision not to, you know,
maybe we'll figure out another way to get it,
get the work done.
Certainly you will.
Terry, I wanna thank you,
first of all, for coming here today,
taking time out of your busy cognitive
and running and teaching and research schedule to share your knowledge with us. And also for the
incredible work that you're doing on public education and teaching the public, I should say,
giving the public resources to learn how to learn better at zero cost. So we will certainly provide links to learning how to learn and your book and to these other
incredible resources that you've shared.
And you've also given us a ton of practical tools today related to exercise mitochondria
and some of the things that you do, which of course are just your versions of what you
do, but that certainly, certainly are going to be of value to people, including me in
our cognitive and physical pursuits
and frankly, just longevity.
I mean, this is not lost on me and those listening
that your vigor is, as I mentioned earlier, undeniable.
And it's been such a pleasure over the years
to just see the amount of focus and energy
and enthusiasm that you bring to your work
and to observe that it not only hasn't slowed,
but you're picking up velocity.
So thank you so much for educating us today.
I know I speak on behalf of myself
and many, many people listening and watching
is this a real gift,
a real incredible experience to learn from you.
So thank you so much.
Well, thank you.
And I have to say that I've been blessed over the years
with wonderful students and wonderful colleagues.
And I count you among them who really I've learned a lot from.
Thank you.
But you know, we're, you know, science is a social activity
and we learn from each other and we all make mistakes. But we learn from each other. And we all make mistakes.
But we learn from our mistakes.
And that's the beauty of science, is that we can make progress.
Now, you know, your career has been remarkable too,
because you have affected and influenced more people than anybody else I know personally,
with the knowledge that you are broadcasting
through your interviews, but also just in terms
of your interests.
Really, I'm really impressed with what you've done.
And I want you to keep at it, because we need people like you.
We need scientists who can actually express and reach the public.
If we don't do that, everything we do is behind closed doors, right?
Nothing gets out.
And so you're one of the best of the breed in terms of being able to explain things in a clear way that gets through to more people than anybody else I know.
Well, thank you.
I'm very honored to hear that.
It's a labor of love for me and I'll take those words in
and I really appreciate it.
It's an honor and a privilege to sit with you today
and please come back again.
I would love to, I would love to, yeah.
All right, thank you, Terry.
You're welcome.
Thank you for joining me for today's discussion
with Dr. Terry Sienowski.
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