Exploring the Intricacies of Memory and Cognition with Dr. Charan Ranganath

welcome to the huberman Lab podcast where we discuss science and science-based tools for everyday

[Music] life I'm Andrew huberman and I'm a professor of neurobiology and

Opthalmology at Stanford School of Medicine my guest today is Dr Char rangano Dr Char rangano is a professor

of Psychology and Neuroscience at the University of California Davis he is one of the world's leading researchers in

the topic of human memory and memory of course is an essential component to our entire lives memory isn't just important

for remembering things that we learn it's also vitally important for setting the context of our entire life meaning

only by understanding where we come from who we were and who we are currently can we frame what we want to do in the next

moments the next day the next years and indeed for the rest of our life this is why for instance that people who have

deficits in memory either due to brain damage or due to age related cognitive decline or diseases like Al aler

dementia suffer so much not just in terms of not being able to remember things for sake of daily tasks but also

for sake of placing themselves in the larger context of their life recognizing family members isn't just about being

able to relate to those family members on a day-to-day basis it's also about understanding the full context of all

one's memories with those people and what meaning a given interaction brings to any of life's experiences so today

you're going to learn how memory Works you're going to learn about things like deja vu you're going to learn ways to

offset age related cognitive decline what the research really says about that and ways to prevent things like

Alzheimer's dementia we also talk about ADHD or attention deficit hyperactivity disorder and Dr rangan shares his own

experience with ADHD how it relates to memory and the tools that he has used in order to combat his own ADHD Dr rangano

has an Exquisite ability to describe research studies in clear terms and to combine that with his own narrative and

life experience in a way that really frames for you practical tools that you can apply in your daily life before you

begin I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford it is however

part of my desire and effort to bring zero cost to Consumer information about science and science related tools to the

general public in keeping with that theme I'd like to thank the sponsors of today's podcast our first sponsor is

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access a free 30-day trial again that's waking up.com huberman to access a free 30-day trial and now for my discussion

with Dr charin ranganath Dr Charon ranganath welcome thank you speaking of memory we go way back we do we do I was

a graduate student when you were first hired as an assistant professor which for those

that aren't familiar with the academic nomenclature and trajectories assistant professors are professors that have not

yet received tenure but now of course you're a full professor and you are a world expert in memory something that I

think occupies the minds of uh all of us even if we're not trying um so that's actually the segue to my first question

which is as we move through our day how much of our cognition our perception is focused on things that are

happening in the present as opposed to being driven by prior memories um you know studies ever been done that

evaluate how often our brain you know switches to thoughts about the past of course we learn about things that are in

our present I know this is a cup because I was taught that um at some point but what I'm referring to is how much of our

thinking on a day-to-day basis is literally in the past well it's interesting that I mean it's first of

all it's a great question to start off with and it's interesting because I actually don't think memory is about the

past I think memory is about the present and the future it's about taking selectively what you need from the past

to make sense of the present and to project to the future I know you're a vision guy right and so if you look at

people's just eye movements right the first time I came into this room I'm sure I wasn't aware of it but I'm sure

my eyes were going all over the place now if I came back to visit you say if you're like oh that was an awesome

interview or whatever right um hopefully but maybe not but let's say I do right chances are yeah so I go and my eyes

will probably go right to the Rick Rubin photo then I'll go right to you know something else to the espresso machine

and so my memory allows me to make predictions about where things are and it's almost preconscious so that it's

happening without our awareness and it's like confirmatory we're grabbing the important stuff and making sure

everything is where it's supposed to be and you can see this play out in phenomena also like change blindness

it's a little bit of a different phenomena but basically in change blindness there's a famous example where

they show a video of people playing basketball and they're passing the ball back and forth and then this guy in a

gorilla costume just walks behind them and about I think it's 40% of the people who watch this video don't see the

gorilla and the reason is is that you're generating these serious expectations

about what's in front of you and so you're not literally seeing what's in front of you you are creating an

internal model a simulation really of what the outside world is and memory whether it's semantic memory which we'll

talk about I'm sure uh your knowledge about the world like the cup thing if it's episodic memory which is your

memory of what happened let's say just a minute ago it's all coming into play and terms of your sense of where you are

right if I just ask you what day is it you will use episodic memory for that tomorrow morning I'm going to wake up in

a hotel room if I don't have episodic memory I will freak out because I'll be like where am I did I get kidnapped why

am I here and that's really the experience of people with memory disorders I mean they have to be in

really familiar environments because it's frightening otherwise right so even I wouldn't necessarily say that

we were never seeing the present of course we are right but our understanding of the present is so

informed by the past that it allows us both to focus on what's important what's non-redundant with what we already know

and it also allows us to detect surprises and find out the things that are unexpected and grab the most

informative stuff as well yesterday I took a brief nap in the afternoon I do this practice of non-sleep deep rest oh

yeah um in the afternoon I got have you teach this to me sometime um yeah it's very restorative for mental and physical

energy I find um but I fell asleep uh toward the end of it and when I woke up I was in a dark room um but I didn't

know where I was for about felt like 10 15 seconds somewhat scary but I I'd forgotten that I was in my solo Studio I

turn turned the room lights down um what is it when we have these lapses in memory as we emerge from sleep or

sometimes um if one has been severely jetlagged um you can experience this disorientation of of place do we know

what that is well a lot of your sense of where you are comes from episodic memory now there's a school of thought that

says that episodic memory which is your ability to remember past events is comes from your ability to understand where

you are and we we have some interesting data from sea liines actually that's speaks to this issue sea lions sea lions

yeah okay we'll get back to that we'll get back to the sea lions but um I would argue that to remember like where you

are when you first get up you have to engage in an active episodic memory retrieval that is you have to figure out

well how did I get here and that takes a moment orienting yourself takes a moment and that because it's it's a little bit

of a controlled memory search right it's not something that's in front of you that reminds you of where you are

initially and you're also in this little bit of a fog when you wake up um I don't know enough about sleep to say but I

would suspect that people probably are in some kind of a stage oneish or just high alpha um these brain waves that are

like very much associated with kind of grogginess as you're getting up neuromodulators are probably super low

so you know so basically not much epinephrine not much adrenaline yeah yeah exactly and so that's going to lead

you to really be slow ining that memory retrieval that you need to orient yourself so like in the clinic if you

want to ask if you want to understand whether someone has a memory disorder one of the simplest things is to ask him

what day of the week is it what month is it um who's the president who's the president yeah right now that's a loaded

question well depends on what time of year relative to the election you ask right um very interesting uh I'm curious

also why it is that most all of us have a stable representation of who we are so my understanding is that even people

with very severe memory deficits don't wake up in the morning and wonder you know who am I or who is this person in

this body that somehow um we remember that we have a self that we are separate from other selves that that kind of

knowledge U might be innate we might be born with it um and that the representation of Self in memory is very

stable is that true well here's what I'll say there it's a real really interesting and complex question

everything's you always talk to a scientist you get it's complicated but um I'll give you a simple of a thing as

I can which is so if you look at patients with amnesia so they have a memory disorder where they can't form

new memories they have a sense of who they are as you mentioned right they it's not like they don't know who they

are and I mean like they know their names they know their biographies and so forth but what happens is at the time

let's say if you had gone swimming and you nearly drowned you had a hypoxia incident or a cardiac arrest or um you

know you had like a traumatic brain injury severe memory deficit right your sense of self doesn't update it gets

kind of stuck and so there is kind of a sense of looking and not expecting yourself to be as old as you used to be

uh as you are because like you're you're stuck in your sense of who you were and I do think I talk my good friend Rick

Robbins at at Davis is a personality psychologist and he studies the development of personality and it does

develop you know it kind of stabilizes in these adolescent years and that's actually also interestingly related to

memory but it does change people do change in really interesting ways so one thing is that people grow more

optimistic on average as they get older um and right yeah yeah that's true so Laura Carstensen your colleague at

Stanford actually has done some really cool work on that topic they become more uh optimistic and yet I would argue that

we become more quote unquote set in our ways because neuroplasticity the ability to re reshape our neur neural circuits

diminishes with age well you know so I think that's overdone a little bit I think you're right you know you

definitely see less dopamine activity for instance as people get older and um uh but what I'll say is that people have

gobs if you have a healthy aging person they gobs of neural plasticity but often what happens is yeah you get stuck in

your ways and that could be related to a few things one is that you get changes in the prefrontal cortex and that leads

you to be less cognitively flexible um it can be also because people just build up so much prior knowledge about the

world that it just becomes kind of ingrained that this is the way it is and it's harder to be surprised I mean you

kind of see this with old scientists right they go like nothing's new everything everything's been disced CED

in 1960 and nothing new has happened since then and by the way for folks listening who are considering a career

in science nothing could be further from the from the truth in fact prior to recording uh you told me a saying that

I've never heard before I don't know if it's cynical or optimistic but if I recall the the quote uh that Dr

ranganath passed along which does not come from him it descends from somebody else not to be named is that quote

science progresses one funeral at a time very very actually uh very interesting statement could be examined from a

number of directions but I agree I agree I mean there's some wonderful let's call them aged scientists with tremendous

knowledge and excitement I mean one only has to listen to like the noo Prize winner Richard Axel talk about his love

of w faction and perception and you can sense his delight and he's getting up there sorry Richard but it's true you're

in your he's in his 70s right hopefully he'll live a very long time but um and certainly science progressed as a

consequence of him being alive and work working on the old factory system but I think what you're referring to is really

important neuroplasticity doesn't necessarily shut down as we age it might even stay open to the same degree as

early adulthood but if I understand what you're saying correctly you believe that it's because people tend to seek out

less new knowledge as opposed to lacking the ability to create new knowledge I believe that's true but that's kind of

that's an opinion I don't have data on that per se but someone's probably looked at this but that would be my

sensus is that a lot of what happens with the way people's lives play out as they get older have to do with their

environment and their experience and that's not to say that I mean yes neuroplasticity does change as you get

older but it doesn't account for the degree to which sometimes people can get stuck and set in their ways and you know

your example of the scientists is such a beautiful example because I look at the scientists who don't get stuck in their

ways right and they constantly challenge their beliefs they surround themselves with a diverse group of people who

stimulate them and they're also open to prediction error that is they're open to saying something could be violating my

knowledge of the world or my my understanding of the way World works so here's just an example and this is I

know I'm going to be free associating all over the place we get into that but it's like what are the coolest studies

that we ever did um and I totally credit my postto matius Gruber for this he came into my lab uh originally German came in

from University College London and he told me he wanted to study curiosity and its effect on memory I'm like this is

just I am being totally closed-minded I said this is just a dumb topic you know it's everybody knows if you're curious

about something you'll remember it better just because you're interested right so he said no no no this is really

interesting and so he did this experiment and I got on board with and I you know we really kind of collectively

it was just this beautiful thing where I was exposed to something new and I got excited about it and so the idea was we

would give people these trivia questions and so it's kind of like a pub quiz right you sit in a pub quiz sometimes

you get a question and it's like I don't know the answer sometimes you get it you I know it sometimes you go I don't know

but God I really need to know the answer to this and you get this itch right or sometimes your listeners I mean they're

probably very curious people that's why they listen to this and maybe some them go to your show notes afterwards because

they want to learn more right so we actually scan people's brains using functional MRI and so we scan them when

they get questions and sometimes they had said I'm really curious to find out the answer to these question sometimes

they weren't curious and then we make them wait about 8 seconds and then or 10 seconds I think it was something like

that and then we show them the answer so they're kind of in suspense it's kind of like you're watching like Breaking Bad

or something back in the day people at commercials and so you're like oh no I got to find out what's going to happen

to Walt right so you're in suspense you need to know the answer to this or you don't care and sometimes you just don't

care you're just sitting around so we show a little face and we say Hey How likely is it you think this person knows

the answer to the question now this is a totally dumb thing to do because they don't know this person they're just

looking at a face they're just making some arbitrary decision but I'll get to why we did that because that was I think

the coolest part of the experiment but let's first get back to the the trivia question so we found that when we looked

at brain activity when we give people the question right afterwards there is a burst of activity throughout the

so-called reward circuit of the brain there's this Ser it's not really a reward circuit as we've discussed

offline it's really these areas of the brain that process the neurotransmitter dope mean and unlike many other

neuromodulators this go all over the place dopamine is much more restricted in its effects and so in the midbrain

near the ventral tegmental area sorry I'm geeking out on this no we've talked about that in this podcast there a

particular I think the key statement that you made that people should hold on to as we progress through this is that

dopamine is not dumped everywhere it's not sprinklered all over the brain it's released in a fairly restricted sites in

order to drive particular processes I think that's sufficient for now yeah yeah and so when we look at functional

MRI we can't measure dopamine but what we see is activity in the dopaminergic midbrain area meaning the area of the

brain around the midbrain and you see it in the nucleus accumbens or What's called the ventral stratum which is

another area that's super high dopamine reward processing area the more Curious people are like on a one to six scale

the more activity you see it's just like this beautiful relationship right and it's not driven by the answer now

there's a reason we probably didn't get it for the answer but it's driven by the question so it's not like they're like

oh I learned something new it's like I want to get this knowledge and so that's part one of the story part two of the

story is we show that face right after the question and if people are curious to find the answer to the question they

get a bump in memory for the faces relative to if they're not curious now the faces have nothing to do with the

trivia question but it's being in that curious state that drives this dopaminergic activity in the mid brain

so there's a whole lot lot of other studies findings from that study but basically I think if God I gotta you

know how sometimes you do a lot of studies me I published like 180 studies so it's like I'm trying to remember

exact I think it was like functional connectivity between the hippocampus and the red brain during the face was

predicting better memory for these faces in general something like that we can put a link to the paper of course and

the show Capt so let me make sure I understand that the um when people are prompted with a question that drives

release of dopamine the amount of dopamine is proportional to how curious they are to get the answer to that

particular question and then the dopamine itself if elevated because they are very curious can

increase the probability that they will remember the answer it creates a millu an environment for better memory but

that can confuse us and make us think that dopamine improves our memory but it's that Curiosity increases dopamine

which increases the capacity to store information that comes subsequent to curiosity beautiful synopsis but I'll do

two cheerful amendments so one is um technically we're not measuring dopamine so I have to be very clear about that

this is bold signal meaning it's you know metabolic activity but it's following all The Usual Suspects of

where you'd expect it to be um the second thing is I do think that dopamine is playing a part and I mean it

definitely facilitates plasticity so I do think it helps in learning the answer for sure and there's a whole Theory

called synaptic tagging which basically says that if you just release a bunch of dopamine and then you have these

potentiated synapses that you can dry plasticity in those synapses even if it's not happening at the same time but

what's really cool is the face has nothing to do with the trivia question the theory that we have is when you get

that bump in dopamine activity You're motivated you're energized to get the answer and you're driven towards the

state of plasticity and now I'm giving you something has nothing to do with this question and boom you got it you

know so when people ask me and they ask me a lot yes how best to elevate their brain

dopamine one reasonable answer based on this study is curiosity to engage curiosity do you know the quote by

Dorothy Parker the cure for boredom is curiosity there is no cure for curiosity um I believe is it was Dorothy Parker if

it wasn't I'm sure we'll find out quickly in the uh uh in the comments on YouTube older people show the effect

just as much as younger people do kids show it just as much as older people do um it's just something that sticks

around so I mean speaking to your point if you are surrounding yourself with things that will stimulate your

curiosity and if you're open to that Curiosity and we could talk about knowledge gaps and all these things that

stimulate curiosity novelty is another one um Richard Morris has some beautiful data on this with rats but um emerel and

I too have some data with humans surprise all of these things I have a whole chapter in my book on this uh

drive that system so the dopamine system the dopamine system so basically if you expose yourself to opportunities to be

proven wrong you expose yourself to new people places situations and you allow yourself to be energized by these things

and not be scared and anxious not be like oh this person's saying something that I disagree with I can't deal with

this you know or oh we figured this out 30 years ago we don't need nothing's new here if you can be open to that I would

argue that you're going to be engaging lots of plasticity and that's something that's preserved in old age recently we

had uh one of the world's experts on romantic relationships uh on this podcast um

Esther Perell to be specific and we talked about a lot of things related to romantic relationships but she said that

one of the most um sustaining factors for romantic relationships over long periods of time is a sense of curiosity

both about the other person but also about oneself and how one changes in the context of the relationship and also

curiosity about where the relationship could eventually go where one to continue to invest in it so this word of

curiosity seems to be a resounding theme um I'm struck by although it makes total sense that curiosity would drive

dopamine release in these uh Pathways that novelty would drive dopamine release in these Pathways and that also

in the Physical Realm dopamine is so important for physical movement yes I don't think this is a a coincidence

right some somehow Evolution organize this neuromodulator dopamine to be involved the way I think about it is in

both a physical movement mhm it's required for it in fact as well as cognitive movement what we're really

talking about is is cognitive forward movement if there is such a thing is there is there a a we're both

neuroscientists but you're the memory researcher is there is there sort of a a word or a framework for thinking about

cognitive movement forward meaning um as opposed to just recycling past ideas and memories the notion of taking memories

and actually putting them as you said earlier into the present to anticipate the future actually forward mental

movement huh that's a really interesting question well first of all I want to be careful and not to say dopamine does

this because it's kind you're it's a trap right it's like well to be clear you observed heightened activity in a in

a dopaminergic circuit so the idea that it would not involve dopamine is is a bit of a stretch but you didn't directly

show that it was do I want to be exact and just say that assigning a single function to a

chemical is you know risky but that said I do believe there's a link one of the things that you see is in Parkinson's

disease dopaminergic neurotransmitter mission is shot and depression is also a symptom of Parkinson's disease it's it's

quite a severe one in fact and uh so what I think one Theory goes is that dopamine energizes us to seek Rewards or

to seek information right so a big part of movement is you move to get something it's a approach right there they talk

about approach and avoidance as basic kind of things that you want to program and so a person with Parkinson's disease

have has a problem with willful movement Tremors and stuff too um but I think that dopamine is involved in this kind

of energizing you to move I think it's involved in energizing you to seek information I think it's involved in

energizing you to seek rewards and uh so I do think there's some kind kind of a common pathway there and speaks to this

issue of the difference which you've talked about and I talk about a lot as wanting versus liking and so Kent barage

at Michigan is a great work on those Rec gobs and gobs of manipulations of dopamine activity and what he finds is

an animal let's say that is deprived of dopamine it will go for rewards just fine it just won't work for them it

won't do the work that you need to get a reward but if you just put it in front of them they'll take it

so what dopamine it is heavily involved with these opioid systems that does Drive um uh reward responses and it's

heavily involved in learning about rewards and that's why you get a big dopaminergic bump when an animal gets a

reward because you're learning about the reward and what predicted the reward there's a little bit of a credit

assignment process that takes place what's interesting is you get this too with actually my colleague at at uh

Davis Brian wilin some beautiful work where he's looked at Trace conditioning which is when you have like a let's say

if you play a tone and you wait a long time and then the animal gets a shock right and so what you uh what you find

is is that the animal learns to be afraid of the tone but it's such a long time in his thing I think it's on the

order of 10 seconds or above the animal has to be somehow doing something to be able to blame that tone for getting

shocked right and so what he found was that there 's this burst of dopamine activity in the locus ruus which

actually known for norp andrine but there's really cool work on dope meaning the LC now modulating hippocampus sorry

to get all nerdy here but no no this trust me this audience likes nerdy I think that's why part of why they're

listening Locus Fus is just a area of the uh of the brain that um tends to sprinkler large Brain areas with

epinephrine which is or norepinephrine nor adrenaline for alertness so somewhat distinct from the dopamine system but

you're telling us it can also releasee dopamine yes that's right and sometimes they co-release from the same neurons

from what I understand and so what seems to be happening is and he's studying this now but what seems to be happening

is it's not that the animal's going oh I just heard a tone I heard a tone and then they get shocked it may be more

like they get a shock and then they get an immediate what just happened and then they get a memory retrieval of the tone

and that allows them to put the two together to learn that this tone caused the shock right and dopamine seems to be

playing a part in that learning process too so it's not just about reward it's really kind of you know the next time

you hear that tone you might if it were a real threat you could actually escape from it right and there's this whole

active avoidance literature that you can look at with these approach circuits that are actually quite useful for

avoiding threats and avoiding punishment so it's really to me I see this role for energizing and that's of rewards I mean

you know I like rewards as much as the next guy right I mean look at how much coffee I drank when I got here um so

it's not that but it's just that it's mobilizing you I think I'd like to take a quick break and acknowledge our

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supply of vitamin D3 K2 again that's drink a1.com huberman to claim that special offer one thing that we talked

about just briefly earlier was this non-sleep deep rest protocol um that is in uh um yoga tradition is called Yoga

Nidra or yoga sleep because you lie down it's self-directed relaxation long exhale breathing to slow your heart rate

etc etc I called it not nsdr not to appropriate it but because the language of Yoga Nidra is a little bit of a

separator for people it sounds a little bit esoteric right and non-sleep deep rest tells you what it is right um

there's a study at the University of Copenhagen I can provide a link to it in the show note captions and I'd love your

thoughts on it that show that people who do this practice this is a pet um Imaging study so positron and tomography

for those that don't know and they see significant increases in strial dopamine in the condition of people that

do this self-directed relaxation as opposed to a more traditional meditation and this is why I say that nsdr is

useful for restoring mental and physical Vigor which translates to this idea that dopamine prepares us for or as a

reservoir for potential movement typically toward rewards and I love that we're talking about some of the other

facets of dopamine because all too often people think about it as pleasure or motivation and certainly it's involved

in motivation um and uh I'm very happy um to learn that uh it's also involved in learning I think that's that's a

that's a that's a novel perspective on dopamine and we hear so much about dopamine do you think that when dopamine

is released as a consequence of curiosity in a way that primes the memory

system that um we become uh entrenched in particular particular behaviors or um routes of uh pursuing curiosity um to

the exclusion of others what I'm thinking about here is a kid um we've seen these data um kids with ADHD um

actually have terrific ability to focus if it's something that they're really excited about really curious about so

you give a kid with ADH who loves video games a video game and they're like a laser so it's not that they lack the

capacity to focus it's that they have a harder time dropping into Focus but it seems that because of the learning ass

um Dimension to dopamine that these circuits could potentially quote unquote

learn that it's video games that provides that feeling of focus to the exclusion of other things meaning how

does one keep a diversification of of um inputs to the dopamine system so that we're

continually driving dopamine through lots of different things as opposed to just social media or just video games or

just pick your favorite yeah yeah thing um because a becoming a functional human being involves the requirement to focus

on many things not just the things we were curious about yeah yeah yeah um I mean to me I talk about this a little

bit in the book but um to me and and if you look at the literature too you can see this a big part of being curious is

the appraisal process so to speak and what I mean by that is saying something happens right let's say

something in your environment happens if you're going to you have a decision to make is this interesting is this

important is this scary and I think the thing is is that you need to be open to that possibility that it's

interesting so like so let me just give you like an example that I um that I often give let's say you're walking in a

neighborhood you're traveling like you do for many of your uh events and you walk into a new neighborhood you haven't

been to it's nighttime kind of poorly lit and you hear a loud noise right you could be like well that's a gunshot I

better hide or I better run or you could be like oh maybe there's a club nearby and there is like a cool band playing I

should go check this out that appraisal is really critical for how you respond and uh so it's not just a matter of

curiosity happens it's a process of cultivation and it's a process of appraisal and so I mean this is I think

you know I'm not a wellness Guru or anything but it's like I think this is one of the cool things about mindfulness

training is it forces you to take the mundane and be curious about it and when you start paying attention to

your breathing uh my friend Mishi Jaws really kind of turned me on to this uh she wrote a book on on mindfulness and

meditation and one of the things that happens is you're breathing you realize wait a minute this one isn't the same as

the last one right or you can do these medit I'm sure you've done this right this uh part of like this sound is

different I'll sit in the backyard doing thanks to you I do this morning 10-minute thing and so I'll be out in

the backyard and I'll be like hearing some sound and I'll be like oh that sound there's a bird there I didn't even

notice that you know and then there's some other sound I'm hearing the freeway that's annoying but I heard it and so

these it's really a matter of paying attention in some ways and being open to it and I think this speaks back to this

thing about as you get older sometimes people find it scary to be in a new place people find it scary to meet a

person who's different from them or so forth I mean I love listening to music that's a little bit out of my comfort

zone some people hate it you know so I I think some of it is sort of cultivating being comfortable with

discomfort think it's such an important theme um I feel like nowadays in part because of the algorithms on social

media we're we are fed things that um feed our U progressively greater and greater scrolling and um dwell time as

it's called you know to they algorithms are measuring clearly how long we dwell on a given image and what's in that

image and Etc um but it would be nice to um cultivate uh an algorithm for curiosity surely it can be done I mean

you got all these smart computer scientists and AI folks um uh and we come into this world naturally

curious um all primates including humans um will visually fixate on anything that's novel right and study it mhm I'm

try and make predictions and gain understanding um maybe now would be a good time for us to discuss a little bit

about the the circuitry involved in memory so that we have that as a template to to digest some other themes

in memory um most people are probably familiar with the so-called hippocampus um which is uh mean seahorse

it looks a little bit like a seahorse although the anatomist had a little bit of an imagination there in my opinion

but um hippocampus um let's add to it prefrontal cortex which you've already mentioned and um and then these

neuromodulatory systems so if we were going to assign a one sentence definition functional definition to each

of those areas um what would you say the hippocampus does all a whole lot of other

neocortical areas let's add those in but I think if we can start with three I think then folks can digest the

hippocampus is controversial I mean it's the most studied area of the brain arguably except for maybe V1 um visual

cortex yeah and uh but I believe and my colleagues do I wrote a big paper with Howard I delate Howard ion bomb and

andinus on this who um you know from Davis and uh we believe that it's about linking various experiences to a context

and what I mean by that is you've got information about smell high level Vision high level semantic knowledge

information right and the hippocampus is wiring is really set up to not understand what's going on so the late

David maru's Pioneer in computational Neuroscience proposed that what the hippocampus is about is what he called

Simple memory it's basically saying I know Andy huberman sorry is okay us to call me Andy that's fine yeah long story

it's a Davis thing you would understand so um uh so I know Andy huberman right but to have a memory of this moment

that's separate from let's say I saw you at some Neuroscience Retreat when we were in uh when you were in grad school

I have to have some part of the brain that doesn't know who you are to some extent right because I got to keep them

separate and so there are the hippocampus what it'll do is it'll form a memory that's not an Andy huberman

memory it's an Andy in this place at this time in this context and that's what allows it to support what's called

episodic memory which is your ability to say I went to Washington DC once and I remember going to the

Smithsonian as opposed to your knowledge about what generally happens in Washington DC oh the president's there

oh that's where a lot of politics happen oh the Smithsonian is a place in DC it's a memory of your being there at a

particular place and time now there's other parts of the brain that allow you to associate that information in a

meaningful way and to be able to to actually expand on that context and create these narratives and these

stories about it and where the prefrontal cortex comes in and it's it's a huge area it's about onethird of the

primate brain so it's just massive uh there are a lot of people who go well there's no real there's a bunch of

different areas and all do different things and I subscribe to the view that that is very true and at the same time

there's a global function of the prefrontal cortex which is what's called cognitive control it's this ability to

say I'm going to regulate my movements and I'm going to regulate my perceptions and my thoughts based on what's

important to me in terms of this higher order goal right so um when I tested for instance patients with prefrontal

lesions I'm sure Mark desposito talked to you about this it's like the Hallmark of them you know they used to say well

the prefrontal cortex it's important for working memory and you could record from neurons in the prefrontal cortex or look

at E from orai signal um and if a person or a animal is holding something in their mind like a phone number neurons

or bold signal and MRI will be highly elevated their activity will be elevated um throughout this period of time where

they're holding in mind but it turns out if you just ask somebody with a major prefrontal asan here's a bunch of

numbers five 2 7 8 you know I ask you to tell them back to me in right order they can do it just fine but now I start to

distract them I move my hands around there's a plane going on you know flying outside the window I had that literally

happen once now they start to bomb it because their attention is not controlled by their goal it's controlled

by the environment around them and so this is where things get really interesting so I once tested a patient

and I'd heard about this but until you see it it like doesn't register really blew my mind so there's a a test called

the Wisconsin card sorting test and we don't have to get into all the details of it but basically it's this test where

people learn some rule about where to put a card on a table right and they don't get told the rule they just learn

it and patients learn this with prefrontal damage learn it just fine right is it that they get a a error

signal or a correct signal if they're doing it in the right direction over time they just kind of the brain figures

it out yeah yeah so maybe I'll give a little bit more background but I don't want to go in the weed no that's okay I

I if I'm correct if I'm wrong I forget the Wisconsin card task details but you know like they they're told to just

start swinging the cards and that the the um the AL the correct algorithm will reveal itself by a series of error and

um correct signals and so maybe I'm taking all the red cards and putting in one pile black cards and putting in

another getting error signals so that maybe I go odds evens maybe I divide by suit if it depending on what kind of

cards they are maybe I organized by even odd alteration and sooner or later the brain figures it out yeah exactly

exactly and you don't need a prefrontal cortex to do that which is surprising but you don't you can do it and so

there's context dependent action and learning without the prefrontal cortex yes but let's

let's unpack this context thing right so now you've been let's say putting all the diamonds in one pile you've been

putting all the Spades in another pile right so now I Chang the rule but I don't tell you and you put the D

Diamonds the Queen of Diamonds In The Diamond pile let's say and now I say nope that's wrong so now you have to

wait a minute that was right all this time what's going on this is like life this is like life right the thing that

used to be used to work for you no longer works so you keep doing this and a person with an intact brain will

eventually figure out okay that's not working I'll try another strategy and then they'll learn the new rule right

it's not easy it's a pain but people will do it this in particular kept on using the old Rule

and so you have to give a series of hints going like H what's your strategy here and they're like they'll tell you

I'm putting it according to the color and then you okay well does that appear to be working for you and they'll go no

they'll just keep doing it they perseverate they perseverate but the interesting thing is he knows it's not

working but he's can't help himself from doing it and so what the prefrontal cortex is

it's not about this declarative knowledge about what you should do and I think this is very deep because I think

often we get moralistic about people's actions especially for people who have head injuries or something like that and

it's like you can have all of these beliefs that you want to have but you need the prefrontal cortex to translate

these high order beliefs things that are very abstract into actual concrete action otherwise what you do is not

going to be dictated by that knowledge so how this relates to memory is we're constantly barraged by information I

think it's it might have said something like 35 terabytes I don't know but it's a big number and the estimates get

bigger and bigger every year so we're barged by information there's no way you can even pay attention to it all right

so you really rely on the prefrontal cortex to be able to say this is what I'm doing right now and everything else

it's noise here's the signal that I need to focus on and that's super important for memory because one of the things you

see in old age is older people are bad at most memory tests but it turns out in the in Labs we kind of overestimate that

and the reason we overestimate it is we're giving them a test which is something hard it requires a lot of

focus and it's not something they do every day but Karen Campbell and Lynn hasher these great cognitive

psychologists did this cool experiment where they had a bunch of other stuff that people were supposed to ignore in

this memory task where they're studying a bunch of things they're trying to memorize a bunch of stuff but there's

stuff going on they're supposed to ignore the older people were just as good as the younger people at

remembering the stuff they were supposed to ignore they were just bad at the stuff that they were supposed to pay

attention to that's so interesting maybe you could say that another time you said it very clearly I got it but say it one

more time because if anyone missed it this is super important older people can they were bad at remembering the stuff

that they were supposed to remember but they were just as good as the older as the younger people maybe even better but

definitely as good as the younger people at remembering the things that they weren't supposed to pay attention to

gosh it it speaks to um almost two um parallel processing streams for memory if I'm not mistaken um or maybe so

what's going on there is it that um one form of memory involves the suppression of information and that circuit is

actually uh quite active in these older people and young people whereas curiosity for um and the ability to

remember and integrate new information is somehow diminished in older people earlier we um we were talking about how

that's not the case that curios if curiosity is intact memory is intact and growing yeah well okay I should say the

benefit of curiosity on memory is intact in older people I I got that wrong I don't know Matias could tell me if I

just email him in a break or something but but uh I don't know if curiosity itself is as high in older adults

selfreported or I would guess no but this is why I asked about movement earlier it's also curiosity is also

linked to your ability to access novel scenarios of course online you can just thumb scroll or click and access all

sorts of novelty um is there any there must be data as to whether or not people in their 70s 80s and 90s are um

scrolling social media uh to the same extent that um younger people are I don't know but I can say two things to

this one is is that definitely there's a lot of work on media multitasking and the short answer is bad for memory

period okay so scroll scrolling is bad for memory well media multitasking is bad for memory scrolling we the tech

thing is a super fascinating area in general it's really how we interact with the tech that's bad

but if you're an older adult your frontal function is not going to be as good you will be more distractable you

will be more likely to go off course and so that scrolling is going to be more potent because as you pointed out the

algorithms are all designed to suck up our attention so psychologist herb Simon came up with this beautiful term called

the attention economy right and so the idea is that the more information that you have in front of you the more

impoverished you are in terms of your attention so there's no such thing as free speech because it's like you have a

limited supply of attention so everything has a cost and so the more information you have in front of you the

harder it is to pay attention to what's important and that's where I think the older adults really lose some of their

their functioning because basically I I talk about in the book and it's not a Perfect Analogy is neurons are

functioning kind of like a democracy in the sense that you know real democracies involve these political coalitions or

alliances right I mean people talk about the right and the left but that's dumb because it's like there really just

alliances between people who like different things and they just form these convenient alliances with each

other right but let's just imagine neurons kind of do this in the brain right and so you have in theory to be

able to pay attention to something some Coalition of neurons has to be firing a lot that is corresponding to the thing

that you're trying to pay attention to but if something is Salient bright shiny loud it's just grabbing your attention

what's going to happen is is that those neurons start to shout down the neurons that are trying to keep you on what's

not shiny but it's important right and so what happens is with the prefrontal cortex you can bias that competition now

that's the term that people have used in literature that allows you so what people have found for is just a really

cool finding again is you can find in the visual cortex neurons that fire when you're see seeing something red and Ne

on set fire when you see something blue let's say right kind of distorting the picture but you get the idea so if an

animal is trying to hold in mind something I say hold on a mental picture of something that's blue what happens is

the blue neurons are firing in visual cortex even though the animal is not seeing blue right it's just they're

thinking about blue you damage the prefrontal cortex nothing so you lose that

selectivity so what's happening is the prefrontal cortex is biasing the competition and saying I

know Blue's not shining in front of you there's no shiny blue thing in front of you right now but I need these neurons

to stay active and so it's doing this modulation to help out the neurons that are keeping the information that's go

relevant so what happens when that communication goes let's say due to hypertension diabetes you get all this

white matter damage that happens with old age and this is really a big thing that is very preventable with the right

protocols so to speak I'll just bre white matter are the fiber tracks the wires that uh essentially that connect

neurons across uh long and short distances exactly yeah and so if you damage those long range tracks the

prefrontal cortex is not efficiently able to bias that competition and so now the inan gets Remembered at the expense

of the important that's that's I think the key thing and uh a lot of that's why why people talk about the prefrontal

cortex as the central executive as anybody who's worked a job knows it's like the executives are useless right he

trying to get an executive to do I mean except for some who are useful but then they don't really run companies very

well there's some CEOs that are doing spectacular things but um yeah well okay we will go

there um controversial shall we say but anyway so uh like a good executive their job isn't to micromanage their job is to

say here's the picture here's my vision for the company and I want everyone to be working towards this goal not you

know sifting through the mail room not paying the bills right and so what happens is is that when you have certain

kinds of things that happen with aging like damage to the white matter that happens uh through essentially tiny

cerebrovascular events most likely and we've done some research on this um in our lab uh in collaboration with Bill

jagus who's now Berkeley and Charlie dearly and you can measure this in MRIs with a A

measure called white matter hyperintensity you use a scan that shows up little bright spots where the white

matter is probably damaged and what you find is is that these people with white matter

hyperintensities actually have memory performance that's as poor as people who have hippocampal atrophy probably in the

earliest stages of Alzheimer's and they're also bad at controlling information even when they

don't have to remember something thing so it's like a double whammy and it's kind of like the executive is trapped in

a in you know a remote place and they got no internet access and no phone and so they can't communicate with the

company as every just doing their own thing right and that's that's a little bit about what what can happen with

aging it doesn't have to but that can happen and you see this to a really great extent in many disorders this is

why so many disorders really affect control and frontal function multiple sclerosis

um diabetes um uh many kinds of things we talked about brain fog many kinds of inflammatory conditions will affect it

um uh depression clinical depressions I've seen people older adults with depression who are cognitively more

impaired than people in the MCI stage of Alzheimer's really yes so depression is dangerous for memory it's terrible for

memory and it seems to be a risk factor for Alzheimer's as well do you think that depression is dangerous for memory

and a risk factor for Alzheimer's because it is by definition anti- curiosity I would probably not say that

and I I would say also I don't know what what I mean you know once you kind of get into these things in the

epidemiological world everything interacts with each other right and there's genetics and there's environment

and blah blah depression means poor sleep which means poor learning which means I think that's a big part of it

you know I think that's a big part but you do okay so let's go back to your question because I do think curiosity is

affected by depression I don't know the research on this but I would be shocked if it isn't and I do think that dopamine

activity is disrupted in depression and your motivation to get anhedonia is the hall one of the Hallmark symptoms of

depression as is rumination by the way which is memory retrieval of preferential negative retrieval of

negative events and cogitating over them I'd like to take a quick break and thank one of our sponsors

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again that's function health.com huberman to get early access to function you probably think a fair amount about

age related cognitive decline and Alzheimer's and I'm just curious um at a personal level uh what are the sorts of

things that you do to try and offset cognitive decline uh you seem to be a very vivacious and curious person um

I've known you a long time and I don't know whether or not you were caffeinated every time we met but you have a lot of

energy you're a very curious person um you just wrote a book um we'll talk more about and you're going on podcast you're

doing a lot of things besides running a you know worldclass research laboratory so clearly a lot of curiosity um what do

the data say about ways to maintain or enhance one's memory capacity with the understanding that

curiosity is probably involved as we talked about earlier but at a at a really basic level um I mean a number of

things leap to mind but I'm just curious what you're um if you had to pick like three to five things that are clearly

substantiated in the data as supporting the maintenance or enhancement of memory as we get older what are those I mean as

a memory researcher I almost find it myself like ashamed when I talk about these things because as you know so many

of the most important factors are ones that are related to just health so for instance uh you mentioned sleep that's a

big one um we can actually there's a beautiful study that speaks to this that was done 29,000 subjects in China and

they followed them up for 10 years now at the beginning of so they divided people into three groups they said okay

here's well what they said is there's six lifestyle factors that we're going to investigate one was I think uh um

engagement in cognitive activities I think one was social engagement one was uh um physical exercise uh not smoking I

think no alcohol but they identify these lifestyle factors that were basically just kind of good lifestyle factors

right so they get people who have four to six of these lifestyle factors going versus uh zero to one of these lifestyle

factors we'll just take the extremes when they start they're all the same 10 years later the people with four

to six lifestyle factors going for for them are performing almost twice as high on memory tests as the people with zero

to one Lifest wow so these are people exercising paying attention to their sleep um social engagement what are some

of the other I believe I'm guessing low inflammatory diet yeah yeah definitely not smoking and uh and smoking and

alcohol um I think were big ones the smoking one is interesting because we know smoking can cause cancer and

cardiovascular risk is is real there although there are some data as I understand that nicotine itself not

smoking vaping dipping or snuffing but that nicotine can be proc cognition and maybe even Pro memory um and nowadays