How to Protect Your Brain from Decline [transcript]

Written by Christopher Kelly

April 24, 2020

[0:00:00]

Christopher:    Well, Josh, thank you so much for joining me this morning. How are you doing? How are you coping with the cordon sanitaire?

Josh:    I guess I'm well as I can be, probably like a lot of other people. Fortunately, I was already working from home and homeschooling my kids, so that meant fewer changes for me personally than probably a lot of people.

Christopher:    Yeah, me too.

Josh:    I still got cabin fever, but so far, that's the only illness we have, knock on wood. 

Christopher:    I was reminded of the last time we spoke about supporting childhood cognitive development when I was listening to Nancy Lublin from the Crisis Text Line on the Masters of Scale Podcast. Are you familiar with Reid Hoffman in the Masters of Scale Podcast?

Josh:    Yeah, I listen to that podcast. I haven't heard that episode though.

Christopher:    It's pretty good. She's talking about how the number of teenagers texting into this crisis line has actually gone down. Can you think of a reason why that might be?

Josh:    I don't know. It could be that their friends are more available now.

Christopher:    What are they not doing that they were spending most of their time doing before?

Josh:    Going to school?

Christopher:    Going to school! School is out!

Josh:    Duh.

Christopher:    So when they're not having to get up for school, what are they doing instead?

Josh:    Well, they're sleeping, right?

Christopher:    Yeah, that's exactly it.

Josh:    All of those social mismatches are erased, right?

Christopher:    Yeah. Isn't that amazing? I thought it's incredible. She talked about how more than half of the normal demographic that text since the Crisis Text Line, young people, all those people have gone away and now it's much older people.

Josh:    There are so many potential lessons that we could learn from this whole ordeal and you just hope that we will. That's a super important thing to make note of like okay, there's a strong signal there. Let's figure that out.

Christopher:    Yeah, I hope so. What do you think? Are you optimistic about that or do you think this is going to be the erasure of a bunch of civil liberties? Do you think digital phenotyping is going to be a thing now where the government has permission to watch you wherever you go? All in the name of tracking a pandemic, of course.

Josh:    I think it gets to this -- it's easy to feel like the future is just going to happen and we're passive, but we do get to determine it, right? If we all make an effort to steer it in the direction we want to go, we can make it better than the alternative. Yeah, I'm cautiously optimistic.

Christopher:    Me too. Well, let's talk about supporting cognitive function as we age. I recently interviewed Kristen Hawkes, the anthropologist, and towards the end of that interview, I pressed her and asked her -- I hope it was a subtle and not too leading a question of how should older people support the cognitive function and prevent as much as possible age-related cognitive decline, and I think she kind of skirted the question a little bit. She seemed much keener to talk about supporting cognitive development in childhood.

Josh:    Right.

Christopher:    So maybe she just didn't understand the question. Maybe nobody knows the answer to that. Maybe I need to talk to her again, I don't know, but tell me about how you first became interested in that question. How do you support cognitive function as you age?

Josh:    Yeah. Well, I am a neurologist, as some people know, and my interest in neurology came through cognitive neuroscience, so I already came into it wanting to focus in on cognitive disorders. That includes age-related cognitive decline. It also includes all of the neurodegenerative disorders, so focusing on that both because they tell us a lot about how the brain works and how cognition works, but also, there are hugely important problems that we have yet to solve. I have spent a lot of time thinking about those issues. I spent a lot of time earlier in my career involved in clinical trials trying to find drugs for those issues, dementia in particular. As you know, as I've talked about before, we have come up empty-handed on all those things, so here I am almost 20 years into a medical career and collectively, at least, we don't have anything that has made an impact on this problem. If anything, it's gotten worse. Numbers continue to grow and we're preparing for a lot more people with either age-related cognitive decline or frank dementia, so it's a huge, enormous societal problem.

    My interest in ancestral health and the personal and professional revelations that that created led me down some other paths towards trying to figure this question out. Ultimately, there's now of the opinion that there's far more that we can do than we're doing or that we realize that we can do. One of the problems that we have faced is that in researching this question of trying to figure out what causes age-related cognitive decline, what causes dementia, we have been focusing on molecular mechanisms.

[0:05:02]

    We've been assembling this and that's where our progress has been in the past few decades, has been identifying molecular pathophysiological changes that are occurring in these scenarios, but we right now are left with this disparate collection of facts. We have all these observations. We have these mechanisms. We don't know how they fit together and we're trying to reverse engineer the problem by studying those mechanisms which, number one, if you don't have any theoretical framework to place those observations into, it's going to be virtually impossible to figure out what's going on.

    That's actually kind of an issue that's being brought about in neuroscience in general, just (a) are we focusing on the right level of explanation here for the things that we're trying to understand, and then (b) if we don't have theory to try to make sense of the data, can we ever hope to do so? That gets back to trying to create a theoretical framework to understand what's happening in these conditions and that's where it ultimately leads into some arguments from evolution to make sense of what's happening and that's where it ties in ultimately to the grandmother hypothesis, but I can get to that later. Anyhow, I gave a talk earlier this year about trying to create a theoretical model that accounts for what we know about these conditions so that we can then -- 

Christopher:    Can you tell us about the talk? I don't think I can reference the talk online yet. Was it recorded?

Josh:    It was recorded. It might even be up by the time this is airing. Yeah, we just have to process those recordings and get them up, but the idea is to put them up.

Christopher:    Okay. Well, Elaine always does a really good job of tracking these things down and putting them in the show notes, and then if it comes out afterwards, I'll just email people afterwards. If you're receiving emails from me, if you're receiving the show notes by email from me then I'll email you later on as soon as that talk is available online, if it's not by the time this podcast airs.

Josh:    I started this talk -- and I'll try to not just give a talk but to keep it conversational, so feel free to chime in if you have questions. I started it by trying to define what are the key observations that we know that we try to make sense of. One is that we know that cognitive function tends to decline with age, or put another way, that youth is associated with remarkably stable cognitive function and also a healthy brain and we don't start seeing signs of loss of cognitive function in multiple domains until midlife, 40s and on. The same is true of the risk of dementia. The age starts later. If you are under 65, your risk is virtually zero. If you are 65 to 74, your risk is about 1% to 2%; at 75 to 84, up to 19%. If you're over 85, over 42%, so you have this sharply increasing risk with age and this protection during your younger years. What's causing this decline as we get older and why is it nonexistent in youth? Another thing that we see is that once these things start, the pace of decline tends to accelerate over time particularly with the dementias, so it's not a linear decline. It's at an ever increasing rate. 

Christopher:    Do you know if you see the same rate of decline in modern hunter-gatherers? I know the modern hunter-gatherers, but my question is, do you think it's a mismatch disease or is this just the way it is?

Josh:    From what we know -- we'd love to have more data, but from what we know, dementias are extraordinarily rare and it doesn't appear that there is significant cognitive decline with age. What we have based on what we know, these both do seem to be mismatch conditions. Also, it's worth noting that even in the early 20th Century when Alzheimer's disease was first described, it was a medical oddity, so how much of that is absence of recognition? I think it's pretty safe to say that the numbers were per capita way lower than they are now.

Christopher:    Right. There's been an explosion along with all the other diseases of modernity. 

Josh:    That was another that is a mismatch disease in that industrial and digital revolution has played a role. Then the question is what's driving this process?

[0:10:02]

    One other thing to mention in terms of the observation from the dementia standpoint is pathologically -- I've mentioned this earlier. You have multiple different pathologies that we see and multiple pathophysiological mechanisms that have been described that are linked to it and no unifying explanation for how you have all of these various things happening at the same time.

    Fundamentally, if we're thinking about this question of cognitive decline, first of all, what we're really looking at is a decline in physiological function over time. If you think about that, you essentially have a complex system. You're trying to maintain order. You're battling against entropy. You have damage that's occurring and you have repair mechanisms. You can accelerate that decline either through increasing the damage or reducing the amount of repair. That's one of the key ideas here and we'll cover more later, but it's this idea that it's not just about the damage side of the equation or the equilibrium. It's also about the repair side, which may matter, in my view, a whole lot more than we've realized. 

    Then just getting back to the overarching framework that we've talked about on this podcast before of playing the game and the quadrant model, ultimately from my perspective, as someone who has an ancestral health view of things, I'm always looking for how we can support the body's own ability to repair and recover and tap into endogenous mechanisms for doing so. We know that that means almost always playing the game, intervening in ways that are evolutionarily familiar. So the dichotomy or the contrast between modern medicine's approach towards these things and the ancestral health view is that here in ancestral health, when we're dealing with a complex system, we want to figure out what does it need to solve its own problems and give it those things for the conditions that it needs to function optimally whereas what we've been trying to do in modern medicine is figure out all the pathophysiological features and see if we can treat those individually.

Christopher:    So it's the bottom-up versus top-down approach.

Josh:    Right. It's the bottom-up, whack-a-mole kind of thing. Clearly, one of the reasons for giving this talk and going down this road again is clearly what we're doing isn't working, right?

Christopher:    Right.

Josh:    This going after molecular targets hasn't paid any dividends.

Christopher:    Right. This, by the way, is why I find the anthropologists so interesting because if the goal is to play the game, my question then becomes what the hell is the game?

Josh:    Yeah. Right. Let's figure that out.

Christopher:    You really need to dig some professor of anthropology out of an office somewhere and have them tell you about our life history because I think that might matter.

Josh:    Right. Exactly. Right. It's usually more than they even realize, I think.

Christopher:    Yes, I think so.

Josh:    The next piece of this is that I guess about 20 years ago or so, we started getting the data that cognitive activity was protective against neurodegenerative disease and cognitive decline, so the thing that kicked this off was the nun study. I don't know if you're familiar with it, but it was a group of nuns somewhere in the northeast that agreed to be tracked over time. It started in the '80s and they were tracking their cognitive function and their health, health markers, and then they also volunteered to have their brains looked at after they died. From that came the findings that cognitive activity or a higher cognitively demanding life seemed to be protective against dementia, so those who had more cognitive activity even early in life but also later on had lower risk of dementia. 

    This is something that I think now is kind of accepted, but was a pretty new idea when this first came out. It has since been supported in multiple other studies, so this has spawned the whole brain training movement and this idea that the brain works like a muscle in terms of you can improve its function and you can improve its health by increasing cognitive activity and increasing cognitive demands. 

Christopher:    Right. Use it or lose it. It's not surprising, is it?

Josh:    Exactly.

Christopher:    If I grow some big muscles and then I sit on the couch for six months, guess what's going to happen?

Josh:    Exactly, yes, forecasting something that we'll get to in a minute here. So you have the brain training movement that comes along. As I said, there's evidence that this is clearly a factor. Practically speaking, most of that has been brain games and so forth that are delivered on a device or online. The data from that is a little bit murky and equivocal, so there may be some benefit, but it's not nearly as robust as we would like to see.

[0:15:09]

    The idea behind why this is helpful is this idea of cognitive reserve, meaning that by engaging in cognitive activities, engaging and learning throughout your life, that you are building a sort of extra capacity in the system so that it takes more to reach a state of decline than it would or a state of functional impairment than it would if you didn't have that capacity. You can think of it like if you have a plane with a backup engine, that cognitive activity is giving you a backup system so that if something goes out, you have something that can compensate at least for a while. That's been the prevailing idea about why cognitive activity is somewhat protective.

    There's other data that would suggest that there's more than that going on and I would argue there's more than that going on. The earliest data was coming from studies on rats where rats that were placed in enriched environments, stimulating sensory environments, would show there'll be increase in things like nerve growth factor gene expression in their brain, in the hippocampus, and you would see that their brains essentially age slower or look more youthful than the controls who weren't in enriched environments. 

    What I think was one of the most remarkable studies was done by Michael Merzenich and his colleagues where they took rats, adult rats, and through an auditory training program for an hour a day for a month, they were able to reverse over 20 auditory processing deficits in the adult brain compared to the young brains pre-training and then those were paralleled by structural changes in the brain. Essentially, one month of training on these different auditory parameters reversed signs of structural and functional aging in the brain. Michael Merzenich, he's a retired professor emeritus now, but I interviewed him on Intelligence Unshackled Podcast awhile back. He's considered the pioneer of neuroplasticity, so he's responsible for not solely, but a big part in ushering in the paradigm shift in neuroscience where we finally recognize that the brain is plastic and the brain is capable of remarkable structural alterations in adulthood. Initially, the work that he was doing that demonstrated that was ignored or ridiculed until it finally become part of the dogma in neuroscience and widely accepted now. It's clearly the case that brains do change. Remarkably recently, this wasn't an idea that was accepted. 

    Interestingly, when I interviewed him on the podcast, I asked him about it because I've always had my own reservations about the idea of cognitive reserve that it didn't seem to explain all the evidence. When I asked him what he thought about the phenomenon of cognitive reserve, he mentioned this particular study. He said that is cognitive reserve. It's more than just this backup system, so the difference there being that what we have in terms of the data on the effects of increasing cognitive demands or specific training is not just that you're building excess capacity, but you're actually restoring the biological hardware. It's not like you lose your engine and you have the backup still working. It's that you're rebuilding the engine after it's damaged. To me, it's an extraordinarily important idea. Once you think about it in terms of -- and he's been beating this drum for a while now. He's trying to usher in a second paradigm shift, but once you realize that this phenomenon exists, it reconfigures a lot of how you might think about this problem of cognitive decline and dementia.

    What we can take away from this line of research is that when you have sustained reduction in demands on the nervous system, you see widespread structural and functional degradation in the brain and that's what we typically refer to as aging. Then on the flip side, when you see sustained increases in demands, you see restoration of those structural and functional degradations, so this is a bidirectional process and it's heavily driven by demands on the system. Then that leads to the idea that you have this regulatory system that is regulating the amount of repair and recovery in the brain.

[0:20:01]

    Obviously, every moment, every day, we have things that we're having to repair and recover from just from the ordinary events of the day. We take out metabolic trash we have. There are all sorts of things depending on the environment we're living in, so it's a constant process. The evidence would indicate here that there is flexibility in that system, in those repair and recovery mechanisms in terms of how much they are upregulated at any point in time. The analogy or the metaphor that I gave there was not a switch, but a slider. You have this analog slider, this dial that can go from low to high, and that position seems to be regulated especially in adulthood by the demands that we're placing on the system.

    If such a slider exists, which the data would suggest that it does, what you realize is that you can then end up in a vicious cycle where if you reduce demands on the system and then your repair slider goes down, that leads to degradation of the system. Once you have enough degradation in the system, it can then constrain the scope of demands that you can then face. Then at that point, you will have a vicious autocatalytic cycle where you're having fewer demands leading to less repair, leading to more degradation, further constraining the amount of demands. This would cause then a self-accelerating or an accelerating process once it begins.

Christopher:    Do you have any reason to believe that this might be a zero sum game? When you look at Kristen Hawkes' work, I think what she's uncovering here is that there's a zero sum game and there's a shift away from reproduction towards -- she uses the words "somatic protection", so protection of the body. It makes less sense at this time to invest in your own offspring that is reproduction and more sense to invest in your grandchildren. In order to do that, you would need to invest in your body somatic protection, but it implies that there's a zero sum game there. It kind of makes sense when you think about it because we see this with the athletes as well, movement, reproduction, growth, repair. They're all a zero sum game. If you do lots of movement, it tends to take away from those other things. You see lack of libido when you over-exercise, for example. I wondered whether that might be the same here like if I'm investing in my cognitive reserve, am I taking away from something else?

Josh:    Right. It is tricky because it does seem like there's at least some element of that of it being a zero sum process. I doubt it really is truly zero sum, but there are definitely constraints. There are going to be trade-offs when you're moving towards something else. There was actually a really interesting study that just came out that was actually showing that maintaining cognitive activity was a better predictor of physical activity. It would look like that physical activity fell behind by how active someone was cognitively rather than the other way around. It's interesting that that may be a lead domino for the process, but it is an interesting thing to add in this discussion. We'll see if that pans out.

    The fundamental idea here then is that it's not just about damage like I mentioned earlier that we have in terms of the equation that we're dealing with. If we think about physiological decline over time, that's going to equal damage minus repair and its cognitive demands are what is modulating that repair side of the equation. What this would mean is that even if you are targeting -- I think everybody would universally agree at this point in time that dementia in particular is a mix of some maybe genetic predisposition plus environmental triggers. The difference between the ancestral view in modern medicine would be that the environment is playing an enormous role and the best frame for understanding it is mismatch, but either way, the focus is generally on what's doing the damage and how do we mitigate that.

Christopher:    Right.

Josh:    The problem is if the repair side of the equation, if those mechanisms have to be on for you to actually repair the system then simply focusing on the damage side of the equation is not going to arrest the process. The analogy I gave is if you're trying to build your muscles, you can eat all the protein you want, but if you don't have a demand signal through resistance training, you won't get growth. So by the same token, if you're trying to arrest cognitive decline or dementia by simply focusing on mitigating the damage without affecting the demand for repair and recovery, you'll have the same scenario. If anybody remembers anything, that's probably the biggest key idea here. The thing that I think is missing from this conversation that needs to be added is it's clear that this is a part of the process.

[0:25:05]

    It's possible that it's even driving the process and give out a little more as to why that could be, but at any rate, it is a factor and we need to know how big a factor it is, and importantly, it's a factor that we can modify considerably. The theory here currently under the working title of Demand-Driven Decline Theory is that cognitive or nervous system demands regulate the position of our repair slider which then determines our mismatch tolerance, so the degree of environmental exposures that we can tolerate and recover from and is a key driver of this process.

    The question then, which starts to get into the idea of the grandmother hypothesis, is why would this kind of phenomenon occur? Why would demands be coupled like this to our repair and recovery systems? It doesn't have to be this way. It doesn't have to be a use it or lose it phenomenon. We know that this is something we see throughout human biology, so it's not just in the brain, but if there are other lines of observation that support this idea, one is the fact that early retirement is associated with early death. There are studies that show if you retire at 55, you're twice as likely to die before the age of 65 as those who retire after 60. Then there are people who a one year older age of retirement is associated with an 11% lower risk of all cause mortality, and these are trying to control for other factors. It's this sort of inversion of age. Simply by doing less, it seems to be increasing your rate of demise.

    There's the widowhood effect that you have a 66% increased chance of death in the first three months after your spouse dies. There's an adage in medicine that one day in the hospital is two days of rehab meaning there's this market decline in physiologic function. It's multi-domain that occurs anytime. You just hospitalize someone and they're in a hospital bed all day. It's essentially saying if you're 60 and you go in the hospital and you spend some time there then when you come out, you're maybe looking like an average 70-year-old, so you've just accelerated what we would call the aging process.

Christopher:    Oh, and I know some people are resonate with all the athletes. If you've ever broken a limb and you had your leg in a cast --

Josh:    Right. Exactly the same thing.

Christopher:    I'll never forget. Jamie, my co-founder, she's a medical doctor, so she understands this intellectually perfectly. I remember once when she broke her leg and her leg came out the cast. Obviously, one of her quads is -- she's a truly elite athlete racing at the UCI level and then the other quad is just like regular, as it would've been, probably worse. Yeah, she was distraught, but of course, it went back. It went back because she just carried on giving the same stimulus that caused it to be that big in the first place. 

Josh:    Exactly, right, but it happens really fast.

Christopher:    Oh, yeah. Yeah.

Josh:    Everything is demand-driven, so why does our body stop taking care of itself? It's not just we lose function. It's clearly a down-regulation of maintaining integrity. When we stop using things, why does it accelerate the aging process? This is a potential evolutionary explanation for this particular phenomenon. As we talked about the grandmother hypothesis, which is a hypothesis to try to explain the length of the human lifespan after menopause, which is long in comparison to other primates, by saying that we're social species and grandmothers enhance the fitness of their genetic relatives by the work they do. So even though they're not reproducing themselves, they are still conferring benefit to their genes that are out in the population because they have relatives out there and they're increasing the likelihood that they will live and reproduce. This brings in the idea of inclusive fitness. Your fitness is not just about your survival, but also, your contribution to the fitness of your genetic relatives is also under selection pressure.

Christopher:    Can I just interrupt you and point out how terrifying that is? It's like that moment when you realize that just because you have the fat gene doesn't mean you're necessarily going to be fat. On the one hand, it's great news because it means you could do something about it. On the other, it's terrifying because now, it's all your fault. I think you've just done the same thing to me here. It's kind of good news in that there's something I can do about this, but it's terrifying that it's not just what I do. It's the population as a whole that might be making the contribution.

Josh:    Absolutely. Essentially here, there is a dark flipside to the grandmother hypothesis, which I call the "better off dead" rule. If you're increasing the fitness of your relatives, you're better off alive, but by the same token, if you are lowering the fitness of your genetic relatives then from your genes' point of view, you're better off dead.

[0:30:07]

    Once you hit especially in post-reproductive years, if you are consuming more than you're contributing then you are from the genes' point of view better off dead. You don't want to be siphoning resources from your relatives if you are yourself incapable of reproducing.

Christopher:    Kristen has published mathematical models that show this that basically prove formerly the grandmother hypothesis that at some point, grandmothering becomes an evolutionary advantage. If you're optimizing to get your genes into the future then it becomes optimal to stop having your own babies at a certain point and start grandmothering.

Josh:    Right, and by the flipside, once you are no longer contributing to their fitness then we are better off not being around.

Christopher:    So the goal is still the same, right?

Josh:    The goal is still the same, exactly. This would mean that if there are regulatory switches that can be modified according to demands, which it appears there are, then the ones that downregulate in the face of reduced demands in the post-reproductive period will be selected for. The reason being is that demands are a very good proxy for your benefit to your drive. You can imagine if you are entirely sedentary and not moving at all, you are dependent on others for survival and resources. If you're doing nothing and your nervous system is getting that signal then odds are you are now siphoning off resources from your relatives. This would then give us a reason -- somebody, when I presented this at a PH Conference, it was Larissa, said, "So essentially, we have a self-destruct button." I was like, "Yes. That's perfect. That's exactly what I'm saying."

Christopher:    That's amazing. It's incredible. You talk for an hour and then somebody summarizes it in six words. 

Josh:    It's like that. It's perfect. That's exactly what this is looking like, is that we have a self-destruct button and it comes from this idea of inclusive fitness that if you are no longer contributing or if you are a net negative benefit to your relatives then you are better off dead. If you have genes that can accelerate that process then those will be selected for. That then begs the question now of what should we do?

Christopher:    Yeah. What presses the self-destruct button? How do I stop that?

Josh:    One, this would in part explain why we're seeing cognitive decline in modern humans, but not in our ancestors. The grandmothers there are doing a lot and they continue to do a lot, so they are maintaining demands. If you look at the architecture-- I guess the first thing I would say is the first step would be let's try to return to what our natural or ancestral pattern of cognitive function would be. There, we want to remain cognitively active and contributing throughout your lifespan. We don't want to just sit around and take it easy as we get older.

    Then there's the question of is it possible to go above and beyond that, and that's where if you go back and look at where is cognitive function maintained strongly and where we don't see decline at all in brain health or brain function, that is in youth. If you look at the nervous system demands over the human lifespan, they are enormous in youth and then they drop off precipitously in middle age and then continue to climb. There are multiple factors, both genetic and cultural, that cause that to happen. This is why I said the good news here is there looks to be a lot more that we can do than we realize. This process is modifiable by modifying the repair mechanisms, but the deck is stacked heavily against us, and the reason being probably the three most cognitively complex things the brain will ever learn are learning to walk, learning to talk, and learning social behaviors.

Christopher:    I was going to say theory of mind is the big one like understanding what's going in somebody's head.

Josh:    Yes, exactly. 

Christopher:    The anthropologists use this word "shared intentionality", which I thought that's the fucking hardest thing that humans learned to do.

Josh:    Yes, exactly, right, all the things that we can't figure out how to train an AI to do yet.

Christopher:    Yeah. Exactly, yeah.

Josh:    These things are scripted, so these are the learning process. This happens and we see it. Every child goes through the same sequence of learning events and this is massively demanding on the nervous system. So just by being a human inheriting human DNA, you are going to be challenging a nervous system enormously in the first couple of decades of life. Then you have all the other factors that are heavily biasing our nervous system demands through heavily frontloading them to early life, so you have not just scripted learning, but then what I call unscripted learning, stuff that's not encoded in the genome and this is the acquisition of new capabilities through our general purpose learning machinery.

[0:35:18]

    Well, in our world today, most of that happens when we're young. When you're young is the time where you go to school. That's where you learn how to play sports and that's where you learn how to play a musical instrument, all these things. That's where you get your education so that you can then use those skills in whatever job you do. We have this heavily frontloaded, unscripted learning as well and it's much more common. Most lessons are for kids, and so we have this whole system that's built up around this idea that all of this learning is supposed to happen earlier in life. Then there are also the demands of adulthood. You're working. You no longer have the time. In the graph that I had, once you become a working stiff, your demands drop off and then you're relying on learned and automated behaviors, right?

Christopher:    Right. You tip away from the exploration and more towards the exploitation like all the computer scientists -- 

Josh:    Exactly. The great thing about the brain is that it can automate so once you've learned something, that behavior becomes automatic. It becomes subconscious and you can do it while thinking about other things. You can essentially reach a point in your life where you can accomplish all the daily needs of adulthood without ever really having to think much and just relying on automatic built circuitry. That is another force conspiring against you, and then there are psychological factors. The older we get, the less tolerant we become of feeling incompetent. We don't like to suck at things when we're older, so we have all these biases obviously that are heavily frontloading how much the demands on our nervous system early in life. I think on the whole, we have vastly underestimated just how great that disparity is.

Christopher:    One thing I'd like to ask you though, would you not agree that this disparity is an environmental mismatch in itself? When you think about it, the idea of schooling and being taught by someone -- the anthropologists, they use these terms like learning by chipping in and learning without teaching. This idea of outsourcing, teaching as an activity to be performed by an adult for children is entirely novel. This is really new within the last few hundred years.

Josh:    Oh, you're preaching to the choir.

Christopher:    I'm sorry.

Josh:    Yeah, 100%. Another thing is -- and I put it in the talk -- it's more than just thinky things. We have this bias as well as to what actually counts as cognitive or intellectual activities and it's thinking stuff, stuff you sit around at a desk and think about. We're ignoring, like we just talked about, talking, walking, social behaviors. Those are crazy, complex stuff, but we don't think about that as a cognitive task.

    You're absolutely right. In school, what we're doing is teaching to this very restricted conception of what human cognition is. So if your goal is to support human cognitive development then what we're doing in school is just this restricted little segment of human cognition in potentially at the expense of other things since everything in the brain is a balance of activation and suppression, so you strengthen one part of the brain and you may weaken others. 

    Yeah, you're already out of the gates with how we do school. It's restricting the scope of human cognitive abilities, and then like you said, we come out like we're learning machines. There's not a lot you have to do to get a kid learning something new especially if they're motivated to do so, and this idea that you have to be the one controlling that processes is --

Christopher:    Yeah, absolutely.

Josh:    But the point being, if you want to optimize your chances of maintaining robust brain and cognitive health over time, you want as best as possible to maintain the cognitive demands of youth and that's a hard thing to do. It's hard to even think of what that would mean. The other thing that you're obviously doing as you're learning all these new skills is you're building these really sophisticated perceptual apparatus that those skills actually depend on to work, so you have to be able to have this fine discrimination of auditory signals and visual signals and proprioceptive signals and all that machinery has to be built. You have this massive perceptual apparatus that you're building, so you're constantly paying close attention to sensory input whereas as an adult, you don't have to do that anymore. Step one in my view in terms of what the heck to do with this information is just to think about the ancestral model and get back to that as much as possible. 

[0:40:02]

    That's where being a grandmother in at least metaphorical sense is super important, but to going beyond a step further is figuring out how to recreate the demands on the nervous system of youth since that's the time where it appears that this regulatory slider is in its maximal position where your repair mechanisms are at their peak. Like I said before, if we're just focusing on mismatch reduction or environmental exposure reduction without the repair mechanisms upregulated then we're not going to modify this process or we're not going to arrest this process. We might slow it down a little bit, so we want to be making sure we're doing everything we can to keep the repair side up. That would mean continuous novel learning throughout the lifespan, so always having a new, complex skill that you are trying to develop and expanding the conception of what you consider a cognitive activity beyond doing crosswords or brain games.

Christopher:    Right, so it's tipping that slider away from exploitation back towards exploration, and then we need to be mindful about -- we already said that shared intentionality and all that kind of stuff is perhaps the most complex stuff that humans do, so is that the type of exploration that you'd recommend?

Josh:    The way I think about it is that all of these early activities are just using diffused cortical networks and that's really what you want to do, is be engaging as much cortical real estate as possible with any new activity. Yeah, anything that involves a social element is going to be taxing. This is why I harp on things like learning to play a musical instrument, learning to dance, things that bring about this whole cluster of human cognitive capacities, but introduce a new element of learning, and ideally, a new perceptual system to develop. 

    If you're learning a musical instrument then suddenly, you have to care about being able to pick out certain details in auditory stimulus that you wouldn't have cared about before. If you can bake that into a learning activity, all the better, but some of the brain training stuff does focus on this a little bit where we're trying to improve the fidelity of a perceptual system. To me, the more natural you can make that, the better and the more likely it is to engage a wider swath of cortex and the more likely you are to care about it as a human. In order for the brain to change and to learn, you have to care enough about the stimulus that you're tending to.

Christopher:    Right, so when someone else is involved, it becomes all the more salient.

Josh:    Exactly. Right. You want to take advantage of all these things to improve salience and motivation.

Christopher:    Right. I was listening to a talk yesterday at the Royal Institute and it was a neuroscientist talking about consciousness. He came up at the end with this statement, "I predict myself; therefore, I am," which I thought was very clever. That's what perception is. It's just making predictions about what's going to happen given these current inputs. Then of course there's another level of complexity. If I'm predicting what somebody else is going to do on top of what my own input are then it becomes an order of magnitude more complex. That's interesting.

Josh:    Those are the key ideas, I guess. One other phenomenon that I didn't mention but that I think most people will be familiar with that gets back to this idea of a self-destruct button is anybody who has had an elderly family member or has worked with older folks knows that people can go downhill really, really fast, so you just see this in all these different ways. There are manifestations of this sort of feed forward loop where a thing to decline just happens super rapidly. I think that's relevant.

Christopher:    Can you give me the algorithm for calculating the better off dead variable? Are we going to see Oura roll this out in the third quarter of 2020? It sends you a message saying, "You're better off dead."

Josh:    Yeah. "You need to walk a thousand more steps today or else, you're better off dead." That's actually brilliant. I love that. Certainly, it's a little bit morbid concept, but it's also useful and motivating, I think.

Christopher:    Yeah, I think so. Let's be really clear about what to do then. Obviously, you're a huge advocate of learning to play musical instruments and dance and singing. That's actually where I hit -- I've been doing the ukulele training that you produced and kindly put on our forum and that's where I get stuck now since you have to sing and play the thing at the same time. 

Josh:    Yeah.

Christopher:    Every time, and I can't -- I've been reading your The Laws of Brainjo book, which is very good. I'm really looking forward to the audio version. Is there going to be an audio version?

[0:45:10]

Josh:    There is an audio version, yeah. I'm recording it, but yes.

Christopher:    Okay. Excellent. I look forward to that. I realized part of the problem is I don't have automaticity. Did I say that right, automaticity?

Josh:    Yes.

Christopher:    I'm putting so much effort into playing the notes that I then have nothing left to be able to do the singing part.

Josh:    Right.

Christopher:    I recognize this from learning other skills especially kiteboarding. For anyone that's ever been kiteboarding, there's all this stuff going on. You have to be able to fly a kite and you have to be able to surf. It's basically surfing. You also have to be able to sail. You're sailing like somebody's sailing a yacht. They're almost sub-routines, and then at some point, they all get good enough to where they're all automatic. They become subconscious. Then there's suddenly this moment that it is a bit like becoming conscious. Suddenly you wake up, you start looking around and you're like, "Oh, look, there's somebody doing the same thing as me over there. There's a wave over there and there's a sea lion." This is almost like waking up once you get this and I realized I just haven't gotten there yet with the ukulele.

Josh:    That, I think, is the flow state too, is when you bump up all of those sub-routines for some complex skill to the point where your conscious mind is free to focus elsewhere and it just feels phenomenal. Yeah, exactly right, singing and playing is the classic rubbing your tummy and patting your head or whatever. It just takes some effort to disentangle that because your brain wants to control them both in a single network and it takes some time to dissociate those two things. It also just takes some mundane type of work where you're just strumming a single chord and singing, just the most basic type of accompaniment that you can do while you're singing until you recognize that the controls are no longer coming from the same place and then you can start to develop the skill further, but it first requires sending that signal that's nope, we're not taking the shortcut and we've got to develop a second pathway here.

Christopher:    Right.

Josh:    I was going to say too, most people in that scenario, there's just frustration like "Why can't I get this thing? I'm incompetent," but if you take the upside to this conception of cognitive decline of dementia, those are actually the situations that are best for you from a brain health perspective. You're getting the greatest signal. You have this activity you care about. It's demanding, and so your brain is going to get a strong signal to change and you'll be upregulating that repair slider versus when I go to play and sing on a song that I know on the ukulele, I can just engage all those automatic circuits, so I'm not really getting a strong nervous system cue.

Christopher:    Right. That's the feeling of you getting stronger. It's what I tell my kids when they're walking up the hill and their legs hurt and their lungs hurt and they're like, "Pick me up. Carry me." I'm like, "Oh no, that means you're getting stronger."

Josh:    Right. "That means you're getting better." That's good.

Christopher:    Excellent. What about teaching then? I think everybody's thinking about that right now with the kids being out of school. I feel like there's a real danger of trying to recreate what's going on in the classroom and that may not be optimal. What do you think? Surely, passing knowledge on to the next generation must be one of these important signals. That means that the "better off dead" button is not activated.

Josh:    Right. Actually, getting to another great cognitive activity is teaching. That's if you're going to rank the list of demanding things that's going to be higher than reading and probably higher than writing. There is certainly value in teaching, but what is a teaching approach that is best for a child? It's clearly not what we've been doing, and trying to strike the right balance of guidance and self-discovery is really the challenge.

Christopher:    Part of the challenge, I think, is that it's different for each child at each particular time. I'm sitting out here, outside recording a podcast. A few weeks ago, I dug a redwood stump out of the ground and there's now a hole. I didn't realize the soil was mostly clay, and so it's filled with water and now it's this mud pit. I could bring my two-year-old boy out here and just start digging in the ground with a stick and he would be stoked like, "Oh! Let me try that. Give me that stick. I want to have a go. This is the best activity I can think of doing in the world" whereas an older kid, maybe not so much.

Josh:    Right. That's almost certainly driven by what his nervous system needs right now, moving a stick around in the mud. It's great feedback. That speaks to the challenge in terms of our broad educational system.

[0:50:05]

    One is that the reason people right now with their kids at home are feeling this pressure is there's this idea of there are these things their kids have to learn and have to know by a certain age or else. That's all driven by college admissions and also all these artificial incentives that are driving what we're trying to get our kids to learn. If your view of what they have to learn is constrained by that then you are going to be in the position of having to teach your kids things that they have very little motivation to learn or you're going to have to figure out how to create that motivation, which is not easy.

Christopher:    Well, that's exactly what I was thinking as you were speaking though. That sensitivity, empathy, theory of mind, shared intentionality, and understanding when your kid is motivated to discover and learn and when they're not, when you're forcing it upon them, is that exactly the sort of thing that we're looking to achieve for ourselves to make sure that we're better off alive?

Josh:    Yeah. Right. Absolutely. That's the thing. If we could be way more flexible in what learning should look like and what sorts of things we want our kids to learn rather than this very circumscribed, specific set of things then you can nurture and cultivate that motivation. You can follow their lead. They're not going to necessarily learn everything in a vacuum, but they aren't going to if they don't care about what it is. Right now, we just waste 99% of the time the kids who are in school because they're learning about things they don't care about, so if you can just expand the conception of what education looks like and that includes not just the types of things they're learning, but how they're learning it, it doesn't have to be sitting down with a book. If we can just take this opportunity to expand our ideas about what education should be and that our real objective here is supporting cognitive and brain development then that opens up so many more possibilities. It can look entirely different from one kid to the next day-to-day. It should not be the same from one kid to the next. I'm sure collectively, everybody's trying to map school at home and make it this uniform thing, which now, that's a constraint that's there because of schools. If you're at home -- 

Christopher:    They're taking away the constraint. 

Josh:    You don't actually have to operate. That's why we tell our kids you don't have to operate under that constraint anymore, which is really ideal. Having to use a one-size-fits-all approach is not the ideal. It's just a necessity based on the model that we have.

Christopher:    Right. You remind me of a funny story my wife told me. One of our friends, they have a kid that goes to the local -- I think it's a kindergarten or maybe it's a preschool. I forget what they call it here in the US. She's five or six years old. There's this old school bus that takes them to the school, and because it's so rural here and the houses are so spread out, it can take an hour and a half to get from some of the houses all the way to the school. Apparently, this five-year-old is their favorite part of the day because guess what? It's totally unscripted. You could do what you want and you can interact with the other kids to do all this social stuff. That's what you really want to do. You don't have to worry about someone telling you what to do. I thought it's hilarious that people think, "Oh, what a waste this is," 90 minutes of the day on the bus not doing something else. That might be the most important part of this child's day, which is terrifying. 

Josh:    I know, right, and that should matter. 

Christopher:    Yeah.

Josh:    That's the other thing and we talked about this in the podcast. The reward signal matters. We should listen to what they're enjoying and what they're not. That's their whole existence. The whole reason they have this prolonged childhood is that they're developing their brain, and what they like and don't like is driven in large part by what their brain is needing at that moment.

Christopher:    One final question for you. We've been talking about this a bit offline. I've just recently finished reading Alison Gopnik's brilliant book, The Gardener and the Carpenter, and I think this carpenter-gardener metaphor is going to apply to any complex system, which is why it's quite brilliant. The difference -- if you've not heard me talk about this before or read the book -- is that in complex systems including childhood cognitive development, you're kind of like a gardener. You throw down some seeds. You don't really know what they are until they sprout. Really, it's about keeping the weeds out, so just prevent the bad stuff from happening, prevent the accidents, prevent the trauma, and everything will be fine. It's less like carpentry where you measure twice and you cut once and it's very clear whether you've met your objective at the end. If the table is flat and it doesn't wobble then you've done a good job. I wonder whether this new theory of yours, this Demand-Driven Decline Theory, is the same thing going to be true too?

[0:55:08]

    So it's mostly about keeping the weeds out like don't eat white flour and sugar and then just sit and watch Fox News all night and you'll probably be fine. What do you think?

Josh:    Well, I 100% agree with that metaphor. That's great. I think one of the most important messages about whether it's neurology or just human health in general is that we are a complex system and we are not applying the types of -- when we're thinking about interventions, we are not thinking as gardeners. We're thinking as carpenters in your metaphor and that doesn't work. That's why we're getting nowhere. We need to be understanding what is this system optimized for, what are the inputs that it needs to function, and like you said, how can we best clear away the impediments. How it all works, we can't engineer specific outcomes. All we can do is to give it the conditions it needs and then let it go to wherever the destination ends up. This goes back to the education thing. We want to control this process, but it's not a system that we have that level of control or it's not a system where that even makes sense.

Christopher:    Well, this has been fantastic, Josh. Tell us about what you've got going on right now. What are you working on?

Josh:    A few things. Hopefully, by the time this airs, it should be up on my website, jturk.net. It should be central headquarters for the things that I'm working on.

Christopher:    Oh, great! Yeah, I love that. Sometimes I wonder what are you working on. I've listened to Derek Sivers in the past and at one point, he was heavily promoting this idea of having a "now" page on your website. I could just go there and see what you're working on. I think it's a really good idea. It's just that nobody could be bothered to update it, right?

Josh:    Right.

Christopher:    I think he still does it. I looked at his the other day, but I think he's the only person in the world that really does it. That's great, so you're creating one hub.

Josh:    Yeah, and also, there are things that I've written or partially written that don't have a clear home, so that's another nice reason to have that including actually this, what I just talked about. The Demand-Driven Decline idea will be up there, but also going to submit it as a paper.

Christopher:    Oh, fantastic! Good for you.

Josh:    Yeah, so that's what I'm working on. I'm also working on transitioning to a virtual clinic with my --

Christopher:    Tell me about that. How does that go down? If you're working with people as a neurologist and the patients have cognitive decline, how does it go down when you've got to have them use some -- are you constrained by HIPAA? I've heard people talking about this. Facebook and Microsoft maybe have clearly developed the best technology for video conferencing, but it's not HIPAA-compliant necessarily. You can't talk to your patients on FaceTime. You have to use this super old, clunky, really awkward HIPAA-compliant thing that all your patients are going to struggle with, even the best of them, let alone the ones that potentially are suffering from cognitive decline. How's that going down for you? 

Josh:    There is a system that's HIPAA-compliant that I've recently signed up on and it works pretty well and it's pretty easy for patients to access. In some ways, maybe it's beneficial -- it's probably actually better especially for those who are in early or middle stages of dementia. Oftentimes, getting someone to a doctor's appointment is a huge challenge and ordeal, and being able to do that from home really is a lot easier. I often thought it's silly for us to be doing these office visits anymore in these scenarios where there's much of a hardship, so there are definitely a lot of advantages. 

    The nice thing about cognition is that you don't have to touch someone to assess a lot of it. I think it affords more time, you're not as pressed for time, and there are a lot of benefits on the patient end. One of the things that's happened too is that they've changed the laws to make it easier for people to do telehealth right now, so I can see anybody in Georgia as a new patient. I'm seeing folks for migraines or memory problems. If you're in Georgia, you can check out jturk.net if you want to connect with me.

Christopher:    Is it true -- I feel like this is true with NBT sometimes that the people that need us the least want us the most. Do you get any patients like that, people like shoppers attack you? I walk down the street and I see all these people I could help, and you're not one of them.

Josh:    Yeah, that is the tragedy, but that's absolutely true that the ones who oftentimes need you the least -- they've already tended to the biggest health levers and you're managing the finer details and you really want to find the people, but this is where maybe -- the fact that the restrictions are loosening up in terms of who can access telemedicine so that you might be able to have that access to a wider range of providers may be helpful, and getting more people in to providers who are a little more lifestyle-minded, "Let's just choose the right drug," this affords you the opportunity, I think, to do a little bit more in terms of the amount of time you can spend and the things that you can talk about.

[1:00:23]

Christopher:    "The Laws of Brainjo" book, will we see that on Audible? How will that work?

Josh:    Yeah, it'll be on Audible hopefully, but for those who like to read the printed page, it is available in bookstores including Amazon for Kindle and paperback.

Christopher:    I like the comprehension that comes with the printed page. I just don't like the sitting part. I'm not very good at the sitting part. It's becoming increasingly difficult to do it on a computer. The temptation to open a new tab or just start doing something else on the computer is so strong.

Josh:    Oh, yes. I can't do it on a computer. I have set times where I do printed stuff, so that's how -- 

Christopher:    Maybe that's what I need to do. I just need to get one of the old school Kindles.

Josh:    Yeah, that's what I've got.

Christopher:    Yeah, not one that's really a computer in disguise.

Josh:    Exactly.

Christopher:    Excellent. Well, this has been fantastic, Josh. I really appreciate you. Is there anything else I should have asked you?

Josh:    I don't think so. I think we've covered it, hopefully, at least. I was hoping to at least -- the ideas that we talked about are important ones to me, so I was hoping I could do them justice. Hopefully, I did, but people can feel free to reach out if they have questions.

Christopher:    I think you absolutely did. I think this would be a really good time to start a discussion on the forum, and if people have got questions then maybe we can get you back on to do some of those questions. It would be fantastic.

Josh:    Cool!

Christopher:    Excellent. Well, thank you, Josh. I really appreciate you.

Josh:    All right. You bet.

[1:01:45]    End of Audio

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