加速学习并提升认知能力

主持人 There's a much more recent study that took again older adults and randomized them across three different groups. One was like a low-intensity group. Another group basically did kind of zone 2 type work on a treadmill three times a week. And the third group did um a high-intensity interval training intervention which was the Norwegian 4x4 protocol. So 4 minutes at 85 to 95% of maximum heart rate. They had a 3minut rest in their protocol. They did that four times over. 有一项更新的研究同样招募 older adults，并随机分为三组：low-intensity 组；每周三次在 treadmill 上进行类似 Zone 2 训练的组；以及采用 Norwegian 4x4 protocol 的 high-intensity interval training 组，即以最大 heart rate 的 85% 到 95% 训练 4 分钟，休息 3 分钟，重复四轮。

嘉宾 That was three times a week. 每周三次。

主持人 Three times a week for 6 months. That's pretty intense. But what they showed was that that highintensity interval training group, they improved their fitness just as well as the zone 2 group, interestingly, but they had much better improvements in hypocample function and maintenance of hypocample structure and MRI scan. And they maintained that benefit for 5 years after the six-month intervention. 每周三次，持续六个月，强度很高。结果显示，HIIT 组 fitness 改善与 Zone 2 组相当；有意思的是，其 hippocampal function 改善、hippocampal structure 在 MRI 上的维持更好，而且六个月 intervention 结束五年后仍保留 benefit。他们苦练六个月，但效果维持了很长时间。

So they worked really hard for 6 months, but that that benefit was maintained for for a really long period of time. Welcome to the Huberman Lab podcast where we discuss science and science-based tools for everyday life. I'm Andrew Huberman and I'm a professor of neurobiology and opthalmology at Stanford School of Medicine. My guest today is Dr. Tommy Wood. Dr. Tommy Wood is a medical doctor and neuroscience researcher at the University of Washington in Seattle. 欢迎来到 Huberman Lab Podcast，我们讨论 science 以及适用于日常生活的 science-based tools。 [音乐] 我是 Andrew Huberman，Stanford School of Medicine 的 Neurobiology 与 Ophthalmology professor。

He is also the chief science officer of BetterBrain, a company that provides free brain health coaching. Tommy is an expert in neuroplasticity and human performance and how science-based protocols can be used to improve your focus, ability to learn, and skill expression. His work applies to everyone from the novice to the elite expert, and for all kinds of skills, cognitive, language skills, athletic, and creative endeavors. 今天的嘉宾是 Dr. Tommy Wood，他是 medical doctor，也是 Seattle 的 University of Washington neuroscience researcher，同时还是BetterBrain 的 chief science officer；该公司提供免费 brain-health coaching。 Tommy 专长于 neuroplasticity、human performance，以及怎样用 science-based protocols 改善 focus、learning ability 与 skill expression。

Today, we discuss the brain states that favor learning and importantly, how to get yourself into those states. We also discuss how to get the most from a learning session. for instance, how long that session should last, how many sessions to do per day, and perhaps most importantly, how to tune your mind and body to get better at learning. 他的工作适用于 novices 到 elite experts，也涵盖 cognitive、language、athletic 和 creative skills。

That's something we don't often hear in the context of learning and neuroplasticity, that our brain circuits for focusing and learning are also capable of plasticity, meaning you can literally get better at getting better. Today, we discuss things like flow states and something called a clutch state, which is a seldom mentioned but critical brain state to accelerate learning and performance. 今天我们讨论有利于learning 的 brain states，更重要的是怎样进入这些 states；也讨论怎样充分利用一次 learning session，例如时长、每天次数，以及最重要的：怎样调节 mind/body，让自己更善于学习。 learning 和 neuroplasticity 语境中很少强调这一点：负责 focus 和 learning 的 brain circuits 自身也有 plasticity，意味着你可以真正变得更善于。

In fact, a clutch state is the state that you want to seek to learn and perform at your best. We also discuss how different types of physical exercise from long slow cardio to brief high-intensity cardio and different forms of resistance training each open the window for distinct types of neuroplasticity and learning. So, this goes way beyond the general discussion about exercise improving your brain. 让自己进步。我们谈 flow states，以及较少被提及但对加速 learning/performance 很关键的 clutch state；事实上，想达到最佳 learning 和 performance，应追求 clutch state。

We get really granular about exactly what types of things to do to improve your brain in specific ways. As a career neuroscientist who has worked on and taught neuroplasticity for decades now, it's rare that I encounter someone with as deep knowledge about the real science and application of learning and plasticity as Tommy has. He's also extremely unique because he has a ton of knowledge about new science-based protocols for plasticity. And he's also an athlete. 还会谈不同 physical exercise：long slow cardio、短时 high-intensity cardio、不同 resistance training，如何分别打开不同 neuroplasticity 和 learning window。这远超一般的“exercise 改善 brain”讨论，会具体到做什么能以特定方式改善 brain。作为从事并教授 neuroplasticity 数十年的 neuroscientist，我很少遇到像 Tommy 这样同时深入理解 learning/plasticity 的真正 science 和应用的人。

We discuss that a little bit at the end as well. So today you will hear a lot of information that I am confident you have not heard on this podcast or anywhere else frankly about exercise, mental training, nutrition and supplementation and much more and how you can leverage each alone and in combination to learn new skills with accelerated speed, precision and durability over time. 他还很独特，因为掌握大量新的 science-based plasticity protocols，而且本人也是athlete，结尾也会谈。因此今天会听到很多你可能从未在本节目或其他地方听过的信息：exercise、mental training、nutrition、supplementation 等，以及怎样单独或组合利用它们，以更快速度、更高 precision 和长期 durability 学会 skills。

I should also mention that Tommy recently released a new book that he wrote entitled The Stimulated Mind: Futureproof Your Brain from Dementia and Stay Sharp at Any Age. It's an excellent book if you're interested in following up on today's discussion and learning more about how you can make your brain better at any age. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. Tommy 最近还出版新书《The Stimulated Mind: Futureproof Your Brain from Dementia and Stay Sharp at Any Age》。如果想继续了解今天内容及任何年龄怎样改善 brain，这是一本很好的书。

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,today's episode does include sponsors. And now for my discussion with Dr. Tommy Wood. Dr. Tommy Wood, welcome. 开始前强调：本 podcast 与我在 Stanford 的 teaching/research role 分开，但属于我向公众免费提供 science 和 science-related tools 的努力。按照这一主题，本集包含 sponsors。现在开始和 Dr. Tommy Wood 的对话。欢迎。

嘉宾 So amazing to be here. Thanks so much for having me. 很高兴来，谢谢邀请。

主持人 Man, this is my favorite topic in the entire world. What is more interesting than neuroplasticity, right? The brain is so interesting, but its most interesting feature in my opinion anyway, is that it can change itself. 这是我全世界最喜欢的话题。还有什么比 neuroplasticity 更有意思？brain 很有趣，而它最有趣的 feature 是能改变自己。

嘉宾 Essentially, that's its core most important function. If it can't do that, literally none of the other functions matter. You could you could argue and it's something that we have to be able to do right until the end of our end of our lives. You have an eclectic research tapestry, right? Today we're going to talk about neuroplasticity, what it is, what it isn't, how to access it for men, for women, different ages, and you also are a high performance coach. 本质上这是它最核心、最重要的 function；如果不能做到，其他 functions。都不重要。而且直到生命结束，我们都必须具备这种能力。你的 research tapestry 很多元。今天会谈 neuroplasticity 是什么、不是什么，men、women、不同年龄怎样 access；你也是 high-performance coach 和参赛的 natural strongman。

You're also a competing natural strongman.

主持人 Uhhuh. 嗯。

嘉宾 Yeah. Yeah. Uh does that mean lifetime no gear? Lifetime. Well, it's tested. I Yeah. Lifetime no gear for me personally, but it's a drug tested version of the strongman sport. So yeah, if you uh if you compete in natural strongman, then you you get tested. Great. So we'll we'll talk about that. I'll resist the temptation to talk about your two boxer pups because I'm a dog lover. That's a different episode. Neuroplasticity. I know what it means to me. 这是否意味着一辈子没用 performance-enhancing drugs？对。我参加的是 drug-tested strongman，个人终身没用。参加 natural strongman 就会被检测。很好，之后谈。先忍住不谈你的两只 boxer puppies，[吸气] 我爱狗，那是另一集。 Neuroplasticity 对我有特定含义。你怎样 conceptualize？

How do you conceptualize it? How do you think people should think about it in terms of wanting to learn things and not forget things? I essentially just think of it as the brain responding to inputs in order for us to then be able to better navigate and survive our environment. And that's why I think it's such a fundamental part of what the brain does. 对于想学习且不遗忘的人，应怎样理解？我把它理解为 brain 对 inputs 作出 response，使我们更好地 navigate environment 并 survive；所以它是 brain 的 fundamental function。

And essentially every time you learn something, interact with something, remember something, the principles of neuroplasticity are engaged, right? you are making new sinapses or strengthening sinapses, weakening other synapses. A lot of people don't realize that particularly brain development, but then also the refining of functions in the brain through neuroplasticity includes the pruning or removal of signapses. 每次学习、与某物 interact、记住某事，neuroplasticity principles 都会参与：形成新 synapses、strengthen 一些、weaken 另一些。很多人没意识到，brain development 以及通过 neuroplasticity refine function，还包括 pruning/removal of synapses。

Often we think about it's all about growth and new connections, but actually it also involves the refining or removal of of other connections that aren't needed. 我们常以为全是 growth 和 new connections，其实也会 refine 或移除不需要的 connections。

That's that's a massive part of of brain development in the first place. And this is a process that's essentially continuously on ongoing and you can think of it as it primary role is so that you can navigate survive the world around you and that's through learning skills through remembering people and things and facts. 这本来就是早期 brain development 的重要部分，而且过程持续进行。它的主要作用是让你 navigate/survive 世界，通过学习 skills、记住 people、things 和 facts。

Um, and where I one of the one of the things that's most interesting to me about neuroplasticity and the way we think about our brains over time is that I think people have uh conflated neurogenesis and neuroplasticity. Mhm. So when we're thinking about brain development, we're thinking about um then also brain function over with with age and either cognitive decline or maintaining cognitive function. We thought that the adult brain was was fixed, right? Neuroplasticity 以及我们怎样看 brain 随时间变化，其中一个我最感兴趣的点是人们混淆了 neurogenesis 与 neuroplasticity。嗯。 [吸气]谈 brain development、随年龄变化的 function、cognitive decline 或保持 cognitive function 时，我们。

Um or or then it was fixed and then it lost function. And this goes all the way back to Kahal who said the adult brain is immutable, right? He told us that you got into adulthood, it finished developing and then it was kind of done. He then at other times also said that changes in the connections between neurons could explain learning. And so there he's talking about neuroplasticity. 过去认为 adult brain 是 fixed，之后只会 loss of function。这可追溯到 Cajal，他说 adult brain immutable：成年时 development 完成，之后定型。但他也说 neuron connections 的变化可以解释 learning，这其实是在谈 neuroplasticity。

But we we kind of got this idea that the brain was essentially fixed as an adult and then you know couldn't change anymore. But that can't be true because you still learn and remember things on a daily basis as as an adult. One of the things that I think we've gotten um confused about is the fact that the adult brain does not make new neurons in many places, right? maybe in the alactory bulbs in the dentus of the hippocampus, but tiny tiny number. 我们却形成了 adult brain 基本 fixed、不能再改变的观念。但这不可能，因为 adult 每天仍在 learn 和记忆。混淆来自 adult brain 多数区域不产生 new neurons；也许 olfactory bulbs 或 hippocampus dentate gyrus 有极少量，对，相比整个 brain 几乎没有新 cells。

Yeah. But like compared to the rest of the brain, they're not you're not really making new cells. And so because of that, we thought, well, we can't then grow and adapt or change our brains as adults. But just because we have a fixed relatively fixed number of cells doesn't mean that we can't change the connections between those cells. And that's happening all the time. And that is, you know, the main principle of neuroplasticity. 于是我们以为成年后不能grow、adapt 或 change brain。但 cell number 相对 fixed，不代表 cells 之间的 connections 不能改变；它一直在发生，这就是 neuroplasticity 的主要 principle。

主持人 Yeah, I like your definition. Um, in part because I agree with it. in part because it encapsulates a lot of uh things including u helping to clear up this misconception that you know we generate new neurons. I think 我喜欢这个 definition，一方面因为同意，也因为它澄清了“会产生 new neurons”的 misconception。

嘉宾 the attractiveness of the new neuron idea is just uh it's so sticky. Um and so we would all love to believe that. Yeah. But maybe there's good reason why we don't add new neurons. Maybe maybe it's uh not adaptive, right? Adding new elements to a circuit is maybe not the best way to change a brain circuit. I think people also like the idea that, you know, every organ in our body turns over its cells. That we're not the same person literally that we were. new-neuron idea 很有吸引力，令人难忘。我们都愿意相信。对。但不增加 new neurons 也许有好理由；向 circuit 加新 elements 可能并非改变 brain circuit 的最佳方式。人们也喜欢“body 每个 organ 都会 cell turnover，所以现在不是原来的自己”这类说法；brain 却基本还是出生时那些 cells，。

The brain is same cells you were born with, minus a bunch of them that die off, as you pointed out. And thank you for mentioning pruning and the and the removal of connections as a fundamental uh aspect of plasticity in terms of um motor skill learning. Um let's say I decide I'm going to um practice billiards. 减去死亡的一部分。谢谢你提到 pruning 和 removal of connections 是 plasticity 的 fundamental aspect。以 motor-skill learning 为例，假设我练 billiards；

主持人 Mhm. and I'm okay now. Hang in there. But let's say I want to get really good as I learn and get better and better. Can we reliably say that uh most of my improvement is the removal of inappropriate action and therefore synaptic connections. 嗯。现在水平还行，但想变得非常好。随着进步，能否说大部分 improvement 来自移除 inappropriate actions，因此移除对应 synaptic connections？

嘉宾 I don't know whether it's the majority. You might know whether it's the majority, but I think that there certainly you it requires both, right? the either the development or strengthening of new connections and then the removal of other connections that decrease accuracy say or that don't allow you to do the exact motion that you were intending to do. This, like I said, kind of goes all the way back to the development of motor skills, say in childhood, right? 我不知道是否占多数，也许你知道；但肯定两者都需要：形成/strengthen new connections，。再移除降低 accuracy、妨碍完成 intended motion 的 connections。这可追溯到 childhood motor-skill development。

The brain has kind of finished developing new neurons sometime around 2 or 3 years old, right? Beyond that point, you're actually primarily removing connections in order to refine uh functions based on the exposures that you have, be they language, motor, social skills, which is what the brain is essentially developing during that time period. So then that continues throughout our entire lives. brain 大约在两三岁完成 new neurons 的主要形成；之后主要通过移除 connections，依据 exposures refine functions，包括 language、motor、social skills——这是该阶段 brain 发展的内容。

And I think that uh something that happens later in life, one of the reasons why we may lose function is because we stop giving the brain inputs to maintain a given function. Therefore, that pruning continues, right? I don't need to learn know how to do this. So, I'm going to refine that away. That's kind of the developmental theory of aging or part of the developmental theory of aging. 之后一生持续。 later life 可能 loss of function，一个原因是我们停止给 brain 维持某项 function 所需 inputs，于是 pruning 继续：“我不需要会这个，就把它 refine 掉。 ”这属于 developmental theory of aging 的一部分。

So in that you know when you're learning a skill as an adult or anytime a big part of refining that motor patterns that you're developing has to be the removal of connections that are or you know the down reggulation of connections that aren't allowing you to to do the skill that you want to do. If you were to tell people, look, you want to keep your brain as young as it can possibly be relative to your chronological age,you should what? 因此任何年龄学习 skill，refine motor patterns 的重要环节都必须包括 connections removal。也就是 down-regulate 妨碍你完成目标 skill 的 connections。如果告诉大家：想让 brain 相对 chronological age 尽可能年轻，应该做什么？

Like it it so this is a general brain health question, but really I'm specifically asking about plasticity and let's make it multiple choice and then you can add things to it. Okay, 这是一般 brain-health 问题，但我特别问 plasticity。 [清嗓] 我们做成 multiple choice，你再补充。

主持人 you should exercise. So it can be multiple things and then we'll talk about which types of exercise. you should continue to do the things that you already know how to do. Yeah. And then third option um not mutually exclusive with the others of course is uh you should try to do new things that you can't already do. I I still toil with this when I look at the literature on neuroplasticity and aging,right? Like yes, use it or lose it is true, 应该 exercise，这是多个答案之一，之后谈哪类 exercise。应该继续做已会的事。对。第三项与前面不互斥：尝试做尚且不会的新事。我看 neuroplasticity 与 aging literature 时仍会纠结。“Use it or lose it”确实成立，

嘉宾 but we're also told that novelty and trying things that we're not good at is an essential component of building out brain circuits, continuing to make them function better as we get older. So, how do you how do you think about all of that? I'll partly answer your last question and then maybe give a framework for how I think about it. 但 novelty、尝试不擅长的事也被说成建立 brain circuits、使 aging brain 继续改善的 essential component。你怎样综合？我先部分回答最后问题，再给 framework。

So when you look at a combination of epidemiological studies and intervention studies in older adults, everything about maintaining cognitive function later in life, you definitely see that those who continue to engage in hobbies and activities that are cognitively engaging or cognitively demanding and that can be lectures, that can be um volunteering, that can be you know reading crosswords, that kind of stuff. those individuals tend to either have slowed rates of decline or better maintenance of function over time and or lower rates of dementia. 综合 epidemiological 和 intervention studies，看 older adults 晚年维持 cognitive function，会发现持续参与 cognitively engaging/demanding hobbies 与 activities——lectures、volunteering、reading、crosswords 等——的人，往往 decline rate 更慢、function 维持更好，和/或。 dementia rate 更低。

That's of course observational, right? But that's usually people continuing to engage in the things that you know they've already been doing, right? So they're holding on to what they've got. Holding on to what they've got by continuing to do that. Okay. Now, of course, it could partly be reverse causation because if you're maintaining function, then you will you're more likely to continue to do the things that that you enjoy doing, right? 当然这是 observational，且通常是继续做已经在做的事。保住所拥有的能力。对。也可能部分是 reverse causation：function 维持得好，才更可能继续喜欢的 activities，所以可能双向影响。

So, there's probably it probably goes in both both directions. However, there's an increasing body of literature that shows that by engaging older adults in novel cognitive activities, you see improvements in function. So that can be language learning. Uh that can be uh complex like coordinative movement or exercise. 不过，越来越多 literature 显示，让 older adults 参与 novel cognitive activities 会改善 function，例如 language learning、complex coordinative movement/exercise、musical training（学新 instrument、music theory、辨别 patterns）。

You see the same things with um like musical training like people learning a new musical instrument or learning um musical theory trying to identify different patterns in music. And you see in randomized control trials improvements particularly in executive function that seems to be most common across those different interventions. But you're seeing um improvements in cognitive function with novel cognitive stimuli. randomized controlled trials 中，最常见的是 executive function 改善；novel cognitive stimuli 能改善 cognitive function。

Uh there's a lot of uh recent trials that have also used types of brain training um things like the pointer trial that was here in the US maintain your brain which is a massive online study done in Australia recently and that's sort of broad cognitive training with like an online cognitive training platform. So again it's it's a new uh or novel um intervention or exposure that seems to provide a stimulus that improves function. 近期许多 trials 还用 brain training，例如美国 POINTER trial、Australia 大型 online study Maintain Your Brain，它们使用 online cognitive-training platform 做 broad cognitive training。这也是 novel intervention/exposure，似乎提供改善 function 的 stimulus。

So, I think both can be or do seem to be important. 所以两者看来都重要。

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嘉宾 Can I ask what um for an example of maybe one or two of the things that were in that large-scale trial from Australia, like just at a at a very top contour level, um older adults, meaning 65 and older, um are doing what? The maintain your brain uh study was actually it was um sort of midlife kind of uh 50s and 50s and 60s mainly and they actually had interventions across four different domains based on risk factors within that given individual. 能否高层举一两个 Australia 大型 trial 的内容？ older adults，比如 65 岁以上，具体做什么？ Maintain Your Brain study 其实主要是 midlife，50s 和 60s；它根据 individual risk factors 在四个 domains intervention：dietary、physical activity、cognitive。

嘉宾 So they had uh dietary a dietary intervention, they had physical activity, they had um cognitive behavioral therapy for those who had um you know some potentially some mental health um concerns and then they had uh online brain training. behavioral therapy（针对潜在 mental-health concerns），以及 online brain training。

Uh there was something similar done in the pointer trial uh which was in older adults now 60s and 70s that was done here in the US that was a replication of an older trial called the finger trial that was done in Finland but what those guys did was something very similar. So it's uh diet, exercise, uh monitoring and and treating uh cardiovascular risk factors and then brain training. So what the brain training looks like um so the points trial is a good example. 美国 POINTER trial 对 60s、70s older adults 做类似 intervention，复制 Finland 的 FINGER trial：diet、exercise、monitor/treat cardiovascular risk factors 和 brain training。

They did um they used a platform called Brain HQ POINTER 使用 BrainHQ platform，

主持人 which is an HQ BrainHQ，

嘉宾 Brain HQ um which was uh developed based on the work of Mike Mzinich um who's you know like one of the godfathers of learning and neuroplasticity right um and they do various tasks primarily focused on developing and maintaining processing speed. Um, some of that evidence goes all the way back to an older trial called active that was done in the US in the '90s. It was still the biggest ever trial of like pure cognitive brain training again in older adults. 它基于 Mike Merzenich 的工作开发；他是 learning/neuroplasticity 先驱之一。 tasks 主要发展和维持 processing speed。部分 evidence 可追溯至 1990s 美国 ACTIVE trial，仍是规模最大的纯 cognitive brain-training trial，同样针对 60s、70s。

So 60s and 70s. They had three different um training groups. The uh and then a control group. Uh the training groups did memory training and kind of like you know pneumonics, memory palaces, that kind of stuff to help them remember. There was reasoning training which is kind of like looking looking for patterns in numbers and letters. And then there was processing speed training where in this example it's visual processing speed. 有三个 training groups 和control group：memory training（mnemonics、memory palaces 等）、reasoning training（识别 numbers/letters patterns）、processing-speed training。

So things flash up on a screen in increasingly small uh increments. So could be hundreds of milliseconds. And as you get better at doing it, that time gets shorter and you have to remember what you saw and where you saw it on a screen. They just published a secondary analysis of the active trial that showed that um those who did processing speed training with uh booster sessions at one and three years had a significantly decreased risk of dementia 20 years later. 后者测试 visual processing speed：screen 上以越来越短的时间闪现内容，可能只有数百 milliseconds；能力提高后，时间缩短，参与者要记住看到什么、出现在 screen 哪里。 ACTIVE 的 secondary analysis 显示，processing-speed training 并在第一、三年做 booster sessions 的人，20 年后 dementia risk 显著降低。

Um and they've done some other studies showing that that kind of training improves co-allergic signaling in the forebrain um which we know is susceptible to um the processes of dementia. So in particular, it's this training uh to be able to improve either visual or auditory processing speed, which is not something that you know, as you get older, you tend to not do activities that require you to process information quickly. 其他 studies 说此训练改善 forebrain cholinergic signaling，而它易受 dementia processes 影响。因此，重点是提高 visual 或 auditory processing speed。

Like driving is probably the main one, but you can do it in sports and music and and other scenarios, but if you're not doing those things, processing speed tends to drop off sometime around 60 years old. When you say uh well I say processing, you say processing uh processing speed. Um are you talking about reaction time, improving reaction time or pushing people to um stay at the edge of of reaction time? 随着年龄增长，人们较少做需要快速处理 information 的 activities；driving 也许最常见，sports、music 也有。如果缺乏这些活动，processing speed 往往约 60 岁开始下降。你我对 processing 发音不同。 [笑] 这里指 reaction time，还是改善 reaction time、让人停留在边缘？

And when I say stay at the edge, I should clarify for people some task where if you go too fast, you make errors. If you go too slow, there's also a penalty 所谓边缘，是太快会 error、太慢也受 penalty 的 task。

主持人 in this scenario. And there are, you know, studies that look at these different functions over time. Probably the biggest one looked at uh data that came from the implicit association test people might have heard of where you get um show these pictures of different things and depending on how quickly you respond it tells you something about like your implicit um you like your implicit thought processes. Um they took some of the data from that. 有 studies 随时间区分这些 functions。最大的一个可能用了 Implicit Association Test data，人们看不同 pictures，response speed 被用于推测 implicit thought processes。

Um this is published in one of the nature journals a few years ago. And what they showed was that um you can separate out reaction time versus processing speed because reaction time is just is a is a very um just the basic of response to a visual stimulus whereas processing requires you is is based on how quickly you can process and remember the information that you're seeing. You actually think Yeah. 几年前发表在 Nature 旗下 journal；结果能区分 reaction time 与 processing speed，因为 reaction time 只是对 visual stimulus 的基础 response；processing 则取决于处理并记忆所见 information 的速度，需要真正 think。

So what they showed in this study was that reaction time kind of slowly decreases on average in a population of it was about 1.2 million people slowly decreases in sort of like from about our 30s and then and then maybe decreases even more once we get past about 60. Processing speed on average tended to be more stable until about 60 years old and then tends to drop off. 研究约有 120 万人，显示 reaction time 平均从30s 缓慢下降，过 60 后也许降得更多。 processing speed 平均到约 60 岁仍较稳定，之后下降。

So in what you're doing in these um training modalities is you're being shown information for a very short period of time and then having to remember what it was you saw and where you saw it. Um so requires you to actually think and you know remember process the information rather than just like responding to a stimulus. 这类 training 会极短展示 information，再要求记住内容与位置，因此需要思考、记忆、处理，而非只对 stimulus 作 response。

嘉宾 So for people that want to jump to the okay what do I do? Um, can we conclude? Okay, if you like crossword puzzles, keep doing them, but do really hard ones for you. If you like lifting weights, continue to challenge yourself with those. If you like to run, you know, push harder. Or should it be we shift domains? You like to lift and run, great. Start swimming again, Andrew. 对想直接问“我该做什么”的人，能否总结：喜欢 crossword 就继续，但做对自己很难的；喜欢 lifting 就继续 challenge；喜欢 run 就更努力。还是应该 shift domains？

I'm telling myself, I used to I, you know, I just noticed over time, it's such a cliche of aging, right? um that you one does tend to become more narrow quote unquote set in their ways. You like what you like, you don't want like what you don't. You get busier. Probably don't actually get busier, but you convince yourself, well, do I'm doing these things and I do plenty of them, so but I'm not doing these other things. Or for those of us, I think this is everybody. 比如喜欢 lifting，也喜欢 run，那就很好；还是重新开始 swimming，Andrew——我在提醒自己。随着年龄增长，人会变窄、变得 set in their ways：喜欢什么、不喜欢什么都固定；越来越忙，或说服自己很忙，觉得已经做很多，不再做其他。

If they really ask themselves an answer honestly,you'd love to hold on to your motor function and cognitive function as long as you can,maybe even improve it. Should we push ourselves to do something that's really far outside the box or maybe sort of current skill adjacent? So, I think of those three categories. What What do the data say? 对我们所有人，若诚实自问，都希望尽可能久地保留 motor/cognitive function，甚至改善。应强迫自己做完全 outside the box 的事，还是 current-skill adjacent？

If you want the greatest effect for the minimum amount of time, assuming you're still going to do all the stuff you normally do, you're going to add something else. 如果仍继续日常活动，想以最少时间获得最大 effect，额外增加的 activity 应怎样选？

主持人 Should it be something really different, slightly different, or just push harder in the thing you do? 应该截然不同、略微不同，还是原有 activity 更努力？

嘉宾 I think it's going to depend a little bit on what it what it is the things that you currently do, right? So like crosswords are a good a good example. Even if you're doing hard ones, if you look at the work of people like uh Gloria Mark, the things like crossword and sudoku, they're less of like a true cognitive challenge, right? It's it's almost has more of like a meditation meditative like effect, right? Which can be a good thing, right? 取决于你现在做什么。 crosswords 是例子：即使难度高，根据 Gloria Mark 等人的工作，crossword、Sudoku 不算真正 cognitive challenge，反而更像 meditation。它有 meditative effect，这是好事：你 focused，但不真正 challenged。

So you're focused but not challenged really. uh whereas if we're trying to build capacity, you need to spend some time doing something where you are both focused and challenged um cognitively. So that can come from um learning new skills be they motor, language, social um and ideally as broad as possible because you're going to get better like overall stimulus as well as kind of like broader potential for for transfer into other areas of of daily life. 若想 build capacity，需要花时间同时做到 cognitively focused and challenged。可来自学习 motor、language、social 等 new skills，最好尽可能 broad，因为 overall stimulus 更好，也更可能 transfer 到 daily life 其他 areas。

In reality, the narrowness of the response or the breadth of the response is proportional to the narrowness or the breadth of the stimulus, right? So, you could get really good at one very specific thing or you could try and learn a new skill that requires a that involves a wide variety of tasks. So, I'll give like like an example is learning a new ball sport, right? that is going to require multiple assets of motor skills, social skills. response 的 narrowness/breadth 与 stimulus 的 narrowness/breadth 成比例。你可以精通一个 specific thing，也可学涉及多类 tasks 的 new skill。

Um, it's going to include both visual and auditory processing that's going to get faster and faster and harder and harder the better you get. So, something like that uh creates a much broader stimulus um than you know if you get very good at one very specific brain training task on like one computer program, right? 比如新 ball sport，需要 motor、social skills，包含 visual/auditory processing；随着进步，它会越来越快、越来越难。这比在 computer program 上精通一个 specific brain-training task 提供更 broad stimulus。

This is one of the main arguments against online or you know digital brain training is that you get very good at doing that one specific thing but it doesn't transfer over to other areas of your life. Whereas some of these broader more complex ultimately more human skills probably give us much broader transfer as well as you know you know because of the the multiple pathways or networks that are being activated. digital brain training 的主要批评就是：只在特定 task 变好，不能 transfer 到生活其他 areas；更 broad、complex、human 的 skills 激活 multiple pathways/networks，可能产生更 broad transfer。

主持人 If my interpretation of what you said is correct, pick something hard. 如果理解正确，就是选 hard 的东西。

嘉宾 Yeah. Ideally, pick something that's a bit outside or really outside your current skill set. Uh that involves motor and cognitive aspects like maybe um and that's kind of tricky to to find, right? I mean, with sport stuff, it feels motor and cognitive because you have to learn the rules of the game. You have to in some cases interact with others. with cognitive stuff. Um the motor skills involved in writing or turning a page, they're not that significant, right? 对，最好稍微或远远超出 current skill set，并兼有 motor 和 cognitive aspects。不太容易找。 sport 同时 motor/cognitive，因为要学 rules、有时 interact with others。

Um even with a video game, I know video games can improve reaction time and visual search and things like that, but basically your thumbs get real real good. I actually went to a video game competition. They have teams. A kid that used to work for me, I was like, "What do you want for kind of end of year gift?" and he's like, I really want to go to this video game championship. And the kids actually who compete warm up their hands. 纯 cognitive activities 里 writing 或翻 page 的 motor requirement 不显著。 video games 虽可改善 reaction time、visual search 等，但主要练得特别好的是 thumbs。我去过 video-game competition；以前的员工把它当 end-of-year gift。

The kids in the audience like have these styrofoam things so they clap so they don't make noise. So they and it was a whole thing. Yeah. So I don't want to take anything away from the the real sport. I I discovered that is playing video games, but mostly what was moving was thumbs and fingers, not a lot of large scale motor activity. Yeah. So, if you had to maybe throw out three or four things that are particularly potent plasticity inducers, what would those be? 参赛 kids 会 warm up hands，audience 用 styrofoam clappers 避免噪音，很完整的一套。对。我不贬低 video games 这项真正 sport，但。主要移动 thumbs/fingers，缺少 large-scale motor activity。

This definitely doesn't have to be super complicated. So, like the things that you mentioned earlier, so because you mentioned exercise and then skills, right? And so, you could do those things separately, right? I would maybe we'll get into why aerobic and strength training do different things to different parts of the brain, right? 如果列三四个特别有效的 plasticity inducers？不必复杂。之前提到 exercise 与 skills，可以分别做。之后会谈 aerobic 和 strength training 对 brain parts 的不同作用，理想是两者都有。

So, ideally, you do a little bit of both. if you don't feel super compelled to go and start a new sport, but you're getting these inputs from elsewhere. Um, and so you you would rather say learn a new language, right, which we have which we have some good evidence for, then that combination is great. But if you're thinking about some of the things that we have very good evidence for that kind of hit multiple um networks at the same time, dancing is probably number one. Lots 如果不想开始 new sport，但从别处获得 physical inputs，可学习 new language；已有不错 evidence，这种 combination 也很好。若想选同时作用 multiple networks 且 evidence 很好的活动，dancing 可能排第一。

主持人 learning a new dance. solo or with someone else? I'm sure we're half joking, but some people dance on their own. Some people dance with someone else. 学 new dance，solo 还是 partner？有些人在家独舞。

嘉宾 So, like dancing on your own in your living room, highly encouraged, right? It's a great form, physical activity. It's fun. You of course the um the best evidence is for ballroom and line dancing, which generally requires and so there are meta analyses of these interventions in older adults showing that ballroom and line dancing have the greatest effect on cognitive function. And so both of those require other people as well as learning you know various sets of of movements. 独自在 living room 跳非常鼓励，是好 physical activity，也有趣；但最佳。 evidence 来自 ballroom 和 line dancing。 older-adult interventions 的 meta-analyses 显示二者对 cognitive function effect 最大。

So you have a you have skill learning you have social interaction and you have a physical activity component. There's probably also the musical component right you have to listen for the timing of the music and those kinds of things that that is its own skill set. So dancing has a a large body of evidence behind it. But then I think you know in the exercise realm you've got all the sort of ball sports, board sports, team sports. 它们需要 other people，也要学 movements sets，因此同时包含 skill learning、social interaction、physical activity，可能还有 musical component：听 timing 本身也是 skill。 Dancing 有大量 evidence。 exercise 领域还有 ball、board、team sports。

Um, I think skateboarding would be a great example. As long as you wear a helmet and don't hit your head uh too often. You know, most martial arts, again, as long as somebody's not punching you in the face too much. skateboarding 是好例子，只要戴 helmet、别频繁撞头。多数 martial arts 也行，只要别总被打脸。

主持人 Something like Brazilian 例如 Brazilian jiu-jitsu。

嘉宾 jiu-jitsu. Exactly. So, like you're um there's a physical component, there's a complex motor skill component. Usually, there's a social component, there's a lot of uh responding, reacting to the environment or your opponent. 正是，有 physical component，complex motor skill、social component，要持续 respond/react environment 或 opponent，也涉及 processing speed。

Uh, right. So then talking about processing speed again but then beyond that there's some really interesting data on some other creative arts that do seem to have some effect on um you know network stability and function in the brain particularly the networks like the front of prioral network that we know is really important for like focus and attention and its function does tend to decrease with age. 另有 creative arts 对 brain network stability/function 的有趣 data，尤其 frontoparietal network；它对 focus、attention 很重要，function 随 age 下降。

Um so uh things like creative or or visual arts um some maybe some similar effects of learning a language um again um uh similar effects from learning to play video games. Yes of course there's no like big motor patterns involved but you're having to do um you know solve complex problems you know uh react quickly to to a changing environment that that kind of stuff. So that's, you know, eight or nine different things that that somebody could try. creative/visual arts、learning a language 可能有类似 effects；学 video games 也有。虽缺大 motor patterns，但要 solve complex problems、快速 react changing environment。

And like just one of those, I think, is going to be a new skill, a new stimulus, often happens in a social environment. Um, a number of different things happening at the same time. 这已经有八九种可尝试。选一个 new skill/new stimulus，最好常在 social environment，能让多种事情同时发生。

主持人 Any particular uh instruments? 某种 instrument 特别好吗？

嘉宾 I don't think anybody's looked at instruments like the difference in different instruments. So I would say no. Pick pick one that you would that you feel motivated and interested to learn. Yeah. dancing by oneself has a lower shame quotient. Well, the shame quot I think might be important, right? 我认为没人比较不同 instruments，所以没有；选择有 motivation 和 interest 的。独舞 shame quotient 较低。

the um you know there's the discomfort of making mistakes and we know how critical that is for learning and so like you're I think some of that can be important too but if you do it in a in a class everybody else is a beginner you're all doing it together maybe that adds a fun component because you can laugh at each other when you don't get it right you know so a few uh years ago I wrote a paper with my colleague Josh Tknet about this idea that um potentially one of the reasons why we lose lose cognitive function as we get older is because we stop giving our brain novel inputs or complex inputs that help maintain function, drive neuroplasticity. shame 可能很重要：犯错的 discomfort 对 learning 很关键。在 beginner class 大家一起犯错，也许更 fun，可以互相笑。几年前我和 colleague Josh Turknett 写 paper，提出 older adults cognitive function 下降的潜在原因之一，是停止给 brain novel/complex inputs，无法维持 function、drive neuroplasticity。

And I think one of the reasons that that happens is because adults hate being bad at things, right? You just like this thought like you you you just imagined it, right? I'm in a dance class and I'm going to suck at dancing, right? I imagine that I'm going to take my wife to to a tango class. It's something I've always wanted to do. When I go in the first time, I imagine I'm going to be like Arnold Schwarzenegger and Jam Lee Curtis in True Lies. Do you ever see that movie? 我认为原因之一是 adults 讨厌不擅长某事。想象自己进 dance class、跳得很差。我一直想带 wife 学 tango；第一次却幻想自己像《True Lies》里的 Arnold Schwarzenegger 和 Jamie Lee Curtis。

But anyway, so right at the beginning, they're like they're spies and they're doing the tango at this, you know, like gangsters mansion or something. And it's like he leans her over, she grabs the rose from the table in her in her mouth. Like I'm going to try that. I'm going to drop my wife and she's going to hit her. She's going to be mad at me and lots of people are going to see and I'm going to feel stupid, right? And so that's why we don't do those things. 电影开头他们是 spies，在 gangster mansion 跳 tango，他把她向后倾，她用嘴从 table 叼起 rose。我若模仿，可能把 wife 摔地上，她生气，大家看见，我觉得 stupid。

But it's so critical to driving those processes of learn of neuroplasticity that we make those mistakes that we have to kind of let go of some of that that we feel as adults like we we think that everybody expects us to be good at everything and the best at everything and you know we shouldn't fail we shouldn't make mistakes but as you have covered many times um it's so critical to to do that and so I think acknowledging that shame component exists and leaning into it is going to be a really important important part of trying to maintain this function over time. [吸气] 所以成年人不做这些。但犯 mistakes 对 learning/neuroplasticity 至关重要，需要放下一部分羞耻；成年人总觉得别人期待自己什么都擅长。我们认为不能 fail、不能犯错，但你讲过很多次，这恰恰必要。承认 shame component 存在，并主动面对，是长期维持 function 的重要部分。

主持人 Couple of quick anecdotes and then some encouragement to do the tango class. Um I'll start with tango. My grandparents on my Argentine side did tango until they're into their 80s. 两个 anecdotes，再鼓励你去上 tango。我的 Argentine grandparents 跳到 80s，

嘉宾 So it can be done but they learned it rather young. Um and Tim Ferrris as I recall talked about this one of his books. Yeah, he learned tango. And um and that gets to the other point which is I want to talk about sex differences in uh results of experiments on in plasticity but when you dance the sorts of dances that we're talking about so salsa tango 所以可行，但他们年轻时学。Tim Ferriss 在书里也谈过自己学 tango。这里也引出我想谈 plasticity experiments 的 sex differences。跳 salsa、tango 这类 dance 时，

主持人 typically this is you know traditionally the male leads um years ago I had a girlfriend who was really into salsa so I went salsa dancing with her in the Bay Area one night and it's it's a tricky thing if you're not skil salsa dancer because basically you're taking your girlfriend to go dance with a bunch of other men, you know, and then you you until you learn. 传统上 male leads。多年前 girlfriend 很喜欢 salsa，我在 Bay Area 和她去跳。若自己不熟练，这很尴尬：基本等于带 girlfriend 去和一群其他 men 跳，直到你学会。

So the the it's it's there are conditions that make it harder, social conditions that make it harder for men to learn than women to learn particular types of dance, unless as Tim did, he got a dance coach, a female dance coach to teach him how to lead and then he learned how to lead and then he was able to dance tango competitively. I think I have that right, Tim. They'll correct me in the comments, but as as I recall, that's the story. So there's that. 因此存在使 men 更难参与的 social conditions。所以 men 学某些 dance 可能比 women 更难。除非像 Tim 找 female dance coach 教他 lead，学会后才能 competitive tango。我记得故事如此，comments 会纠正。

Um not that following is is trivial. It requires some skill. But there the if the person again traditionally the male can't lead the whole thing it it doesn't work 并不是 following 很简单，也需要 skill；但若传统上担任 lead 的 male不会 lead，整套 dance 就无法进行。

嘉宾 right. So um I just made you more nervous about going to this class but you should do it because um I had a roommate when I was a posttock who was a neurology resident at UCSF and she would go do tango late at night and she would come back a different person. 我让你更紧张了，但仍该去。我做 postdoc 时有 roommate 是 UCSF neurology resident；她深夜去跳 tango，回来像另一个人。

And so this is like the other piece here is you know it seems that when we are trying something truly new that involves interactions with other people and we go into that willingness to enter beginner's mind or whatever it is embrace the shame and as we start to get even just a little bit better at something. I mean it almost seems like there's this kind of halo around the rest of our life. We go to work the next day differently. 另一个点是：当我们尝试真正新鲜、涉及他人的活动，并愿意进入 beginner's mind，拥抱 shame，哪怕只进步一点，似乎会给生活其他部分带来 halo。

We interact with people differently. like our nervous system is changed. What do you think that is? I mean, we can make up stories about chemicals and maybe we should because they're likely to be true. What do you think that is? That like general change in arousal like you're sleeping better, you're you're more excited for the other things in life when you're trying to learn tango and you get just a little bit better. What is that? 第二天工作、人际互动都不同，像 nervous system 被改变。这是什么？可以编 chemicals 的故事，也许会是真的。是 general arousal change？睡得更好？学 tango 进步一点，便对生活其他事更兴奋？

主持人 I don't think I would make up anything about about chemicals. I think you could boil a lot of it down to we like to be good at stuff and we like to overcome things, right? There's just like this like core need to be challenged and then to overcome those challenges. And I think there's a lot of downstream effects of of not doing that and they could be um you know related to mental health. It could also be related to physical health, right? 我不会编 chemicals。我认为可归结为：我们喜欢擅长事情、喜欢 overcome things。存在一种 core need：被 challenge，再 overcome challenges。缺少这种过程会有 downstream effects，可能与 mental health、physical health 相关。

because we think about physical and and um cognitive or um you know stressor psychological related challenges and and the process of overcoming them because that's what really drives you know a lot of physical or or mental psychological growth and I think that's something that you know fundamentally is part of what we need on a daily basis and so you did this thing that you were bad at and you got better at it and you proved to yourself hey I'm capable I'm able to overcome challenges is I'm able to you know engage and and do difficult things and I think the psychological benefits of that you just that process of engaging with a challenge overcoming it uh working hard to do that um I think that's just you know almost like a core psychological need that we have and then that transfers to all these other things oh yeah I can do these hard things I'm going to do that other thing I'm excited to try something else that's difficult I'm excited to challenge myself again and it needs to be something that feels uh meaningful, feels difficult enough that you have the ability to overcome with some dedicated practice or you know focus time working on it. 无论 physical、cognitive 还是 psychological/stressor-related challenges，overcoming 的过程驱动很多 physical、mental、psychological growth。这似乎是每天的 fundamental need。你做了原本不擅长的事并进步，向自己证明：我有能力 overcome challenges，能 engage 并做 difficult things。与 challenge 互动、努力 overcome 的 psychological benefits，几乎是 core psychological need，并 transfer 到其他事：我能做 hard things，也想试另一个 difficult thing，再 challenge 自己。

If it's too hard, right, you can have the opposite effect, right? Like making something so difficult somebody can't do it and they just fail again and again and again, right? That that can obviously have the opposite effect. But something that you know you can get better at, you know, you can work on, you can see progress, right? I think all of that then has all these knock-on effects. 任务要 meaningful、足够 difficult，但能通过 dedicated practice/focused time overcome。太难会有反效果；若反复 fail，显然可能产生 opposite effect。应能通过练习看到 progress，于是产生 knock-on effects。

嘉宾 Maybe we could talk about flow for a second. you know, one of the most bastardized terms in uh neuroscience performance psychology and the rest. When Cheeks Mahai talked about it initially, um when he really defined the term, it was about um being engaged in a process where you have a certain level of skill, but the thing you're trying to do is just beyond your skill level. So, really striving a bit and that kind of general sense of well-being that can come from that. 谈谈 flow，这是 neuroscience/performance psychology 中最被滥用的词之一。 Mihaly Csikszentmihalyi 最初定义flow，是投入某 process：已有一定 skill，而目标略超当前 level，需要努力，并由此产生 general well-being。

Nowadays, I think people assume flow is when you are able to do something in the absence of kind of feeling of effort. It's like you just you you get the magic power kind of thing, which is not what flow was originally intended to to mean. I'd like to know how you think of this concept of flow and whether or not it's even a meaningful term. And I I you know I tip my hat to Stephen Cutotler and others who have written about it and and studied it and 如今人们却以为 flow 是完全感觉不到 effort、像获得 magic power，这不是原意。你怎样理解 flow？它是否仍有意义？我向 Steven Kotler 等研究和写作它的人致敬。

主持人 a great respect for Stephen and um what he's done uh with the concept and and uh and I think it's a meaningful concept but I don't think we really know how to define it. And I think this is important in the context of plasticity because I think what we see in Harry Potter movies and sci-fi and um you know fight club and everything else is that suddenly we're just going to be endowed with these powers just because we want them and need them and that is not how it works. 我很尊重 Steven 和他的工作。概念有意义，但我们不真正知道怎样 define；这在 plasticity context 很重要。 Harry Potter、sci-fi、Fight Club 等作品让人以为，只要想要或需要，就会突然获得 powers；现实不是这样。

嘉宾 Yeah. 对。

主持人 So is flow an expression of skill or is it the striving to attain a skill? flow 是 skill expression，还是为 skill 努力？

嘉宾 I think of flow as the maximal expression of a complex learned skill. like you said, you're like right at the edge of your capabilities, but you're still managing to maintain um maintain function whatever whatever skill it is that you're you're performing at. 我认为 flow 是 complex learned skill 的 maximal expression：位于 capabilities edge，。

The thing that really frustrates me is that because of that or you know some version of their definition of flow, people like well I've always got to search for flow like everything happens in flow and like we need to be in flow all the time which doesn't make any sense to me whatsoever. There's two different parts of this. So one is that people assume that for optimal performance you need to be in flow. That is not true. 仍能 maintain function、完成 skill。让我烦恼的是，人们因此觉得必须一直 search for flow，好像一切只在 flow 中发生，这完全没道理。这里有两部分。第一，人们假设optimal performance 必须处于 flow，这不正确。

Um flow is one version of your of your of of being able to you know perform at the best of your abilities. If you think about this in terms of sports performance there might be broadly two states associated with top level performance. One is flow states the other is clutch states. Flow 只是发挥最佳能力的一种 state。 sports performance 顶级表现大致有两种 state：flow 与 clutch。

And so a clutch state um you are still at the optimal level of arousal right if we think about the arousal curve and performance which we can come back to but so at the optimal level of arousal which is required for you know you to perform the skill that you're trying to perform but when you're in a clutch state it still feels like hard work right so like there are you you could talk to any athlete about a time that they um they performed well they won they you know they did at the best of their abilities but it was hard cognitive work it hard physical work. clutch state 同样处于 optimal arousal level，也就是完成 skill 所需 arousal；但 clutch 仍感觉是 hard work。任何 athlete 都有这种经历：赢了、做到最佳，却付出艰难 cognitive/physical work，是一场 slog，但仍表现很好。这就是 clutch state。

It was a slog, but they still managed to perform well. That's a that's a clutch state. And people can perform at the best of their abilities in clutch states. Um, and you know, even though they're not in flow, it's not all coming to them easily, right? It requires them to like really focus and work hard to get get the job done. And both of those are perfectly reasonable states in which to perform. 即使不在 flow、事情不自然顺畅，人也能达到最佳能力，需要高度 focus、努力完成。两种都是合理 performance states。从运动员实际表现看，必须 flow 才能 perform 的假设不正确。

And assuming that you have to be in flow to perform just isn't true if you look at like how you know athletes perform in the moment. The other side of it is that some people have intimated that flow is required for learning or like optimal learning happens in flow which doesn't make any sense. 第二，有人暗示 learning 需要 flow，或 optimal learning 发生在 flow 中，这也说不通。

Right? If we if we talked about making mistakes and errors and friction required for learning that is not conducive to flow because it's uh it can be stressful, it could be frustrating and sort of the other side of that is if you know flow is expressing your skill. If you want to get better at that skill, you have to work even further beyond your current capacities which which will move you out of flow, right? 前面谈到 mistakes、errors、friction 对 learning 必要，而它们不利于 flow，因为会 stressful、frustrating。另一方面，flow 是表达现有 skill；想进一步改善，就必须超出 current capacities，friction、mistakes、errors 会把你移出 flow。

because of like the friction, the mistakes and the errors that come from that. So I think yeah, flow is super interesting and I I wouldn't pretend to be an expert in flow, but there are all these other states where learning happens, where performance happens that aren't flow and that's fine, too, right? But sometimes it's hard and that's okay. 所以 flow 很有意思，我不假装是 expert；但 learning/performance 还有许多非 flow states，也完全正常。有时过程很难，也没关系。

主持人 I'm so glad you're here. I I've been looking for this conversation for well since I started the podcast because I completely agree about flow and the misunderstanding of the concept of of flow. I've never heard of a clutch state. Um is that a term that you coined or something? 太高兴你来。我从开 podcast 起就在找这场对话，因为完全同意 flow 被误解。我从未听过 clutch state，是你创造的 term 吗？

嘉宾 No, no, it's in the sports psychology literature. They'll talk about 不是，来自 sports-psychology literature。

主持人 that's why I haven't seen it. Yeah, cuz I'm very familiar with the neuroplasticity literature, but I've I've never heard of it. Maybe I'm just not up to date on my reading. 难怪我没见过；我熟悉 neuroplasticity literature，。

But um thank you for introducing clutch state which is when one is performing well but it's it is involving and this is a term I did make up sort of some limbic friction like you have to push yourself you're feeling constrained it's that you're at that edge where it's there's real challenge you're not you're definitely not in flow. Yeah. Uh, fantastic clutch state everyone. 也可能阅读没跟上。谢谢介绍 clutch state：表现很好，却包含——借用我创造的 term——limbic friction，需要 push 自己、感到 constrained，处于真正 challenge 的 edge，绝不在 flow。对。很棒。大家学习、理解、拥抱 clutch state。

Um, learn it, know it, embrace it, um, live there for some period of time in your life across your lifespan. Uh, and you'll be better off. I I I mean that. 在 lifespan 某些时期活在这种状态，会更好。

Maybe we could drill into this a little bit more because you know several times on this podcast or more we've talked about the anterior midsulate cortex the structure that you know maintains size and super aers who take on hard things and you know this area of the brain that seems associated with tenacity which when stimulated people feel like an impending challenge there's actually neurosurgery experiments done by Joe Parvey at Stanford people feel like oh there's an impending challenge I'm going to lean into it this is sounds more like the clutch state than certainly and flow state. 我是认真的。再深入：本节目多次谈 anterior midcingulate cortex；super-agers 和主动做 hard things 的人会维持其 size。该 brain area 与 tenacity 相关，刺激时人会感觉 impending challenge。 Stanford 的 Josef Parvizi 做过 neurosurgery experiments：人会觉得挑战将至，准备迎上。这更像 clutch 而非 flow。

So maybe the thing we need to embrace is the clutch state. It's pretty catchy. It's not quite as catchy as flow, but but I I like it because um it has an element of like friction kind of written into it. You heard it first from Tommywood folks uh not me. A good friend who uh comes from the special operations community. 也许应拥抱 clutch；名字虽不如 flow catchy，却把 friction 写在里面。各位最先从 Tommy Wood 听到，不是我。一位来自 special-operations community 的朋友多年前和我谈 performance，说有 unskilled、skilled、mastery、virtuosity 四层。

Uh we talked about performance uh years ago and he said, "Well, there's unskilled, skilled, mastery, and virtuosity." M okay cool and he said virtuosity is when someone who has mastery pushes out to an edge of effort where they're sort of inviting in the unknown. They don't quite know what they're going to do next. They they have some semblance of an idea like they're not being um haphazard but there's an inviting in of the unknown and they find themselves at a new level. virtuosity 是拥有 mastery 后，向 effort edge 推进，主动邀请 unknown；不完全知道下一步会做什么，虽有大致 idea，并非 haphazard；但允许 unknown 进入，于是到达新 level。

I've probably mentioned this documentary four times in the last four episodes, but when Andy Stumpf, former uh tier one SEAL operator, came on this podcast, former wings sutor,Red Bull High Performance team came on here, he suggested a podcast that I'm now suggest he suggested, excuse me, a documentary that I highly recommend, which is The Dark Wizard, which is about Dean Potter, who was a free climber, a free solo climber, turn wings, etc. 我最近四集提过这部 documentary：前 Tier One SEAL operator、wingsuiter Andy Stumpf 参加节目时推荐，我也强烈推荐《The Dark Wizard》，讲 free climber/free solo climber 后转向 wingsuit 的 Dean Potter。

And you see in that documentary how somebody who's pushing to their edge and a little bit beyond where the consequences the death consequence is able to access levels of skill that are like jaw-dropping I think even to him. 片中可见一个人在有 death consequence 的情况下推向 edge、稍微超越，access 令人震惊、也许连自己都惊讶的 skill level。

嘉宾 Mhm. So does that make sense? Like is that sort of how you think about unskilled skilled mastery virtuosity? Do you think virtuosity is like where someone's like, "All right, I've mastered this thing. 嗯。这符合 unskilled、skilled、mastery、virtuosity 吗？

Now put me in a situation or I'll put myself in a situation where I don't know what's going to happen and maybe it'll all go wrong, but when it doesn't, new levels of performance emerge as it's described that way." Um, because you people might talk about virtuosos in a skill just because like they're so much better than everybody else, right? But like that that that definition requires a specific scenario and moment of performance, right? virtuosity 是否就是：我已 mastered，现在把自己置于不知道会发生什么、可能全出错的 situation；若没有出错，就 emergent new performance levels？按这样描述，人们也许只是因为某人在 skill 上远超其他人，就称其 virtuoso；但这个 definition 要求 specific scenario 和 performance moment。

So then that sounds a lot like how I would think about flow,right? And so like when you when you look at some of the classic descriptions from individuals who've been in that kind of level. So like um there's one from so I I do a lot of work in Formula 1. So there's one from Aton Center where he's from who? I'm sorry. and Senna. Um,the driver. Sra. Yeah. Senna. Senna. Excuse me. Sra is David Senna. The great podcaster. 那听起来很像 flow。经典描述中，有些人达到这种 level。例如我做很多 Formula 1 工作，Ayrton Senna 有一段描述。谁？抱歉。 Senna，driver。

He's the He's the virtuoso of of uh performance and business and finance podcasting. Don't let any of your uh F1 loving friends hear that part of the podcast. No, no, I like Sen. Some people consider him to be the the the best Formula 1 driver of all time. He died tragically in a in a crash. Um but there's this um famous quote from him where he's driving in the Monaco Grand Prix and basically what he describes is that he's like going faster and faster and faster. 我说成了 Ezra。 David Senra 是伟大 podcaster，是 performance、business、finance podcasting 的 virtuoso。别让 F1 朋友听到。不，我喜欢 Senna。 [笑] 有些人认为他是史上最佳 Formula 1 driver，他 tragically 死于 crash。

He's like this is beyond my capabilities. Like he doesn't feel like he's actually connected to doing the thing. It's just kind of like happening. It's exact it's exact like he's going seconds faster around the lap than anybody else. And so like that's kind of what like he is so good, right? 他描述 Monaco Grand Prix 时不断开得更快，觉得已超出 capabilities，像自己没有参与，一切自然发生；lap time 比别人快数秒。

he achieved mastery and in that in that moment he's displaying virtuosity in that kind of um in that under that kind of definition and so like that that feels like there's a lot of overlap there. 他如此优秀，已达到 mastery；那一刻按这个 definition 展示 virtuosity，所以有大量 overlap。

主持人 Yeah. Ever since seeing this uh Dark Wizard uh documentary which I've watched twice all the way through because it has a mental health component. It's a it's a brilliant and beautifully shot documentary recently released. I um I think about this virtuosity thing like constantly. Uh, but I I love this notion of the clutch state because it sounds to me that that's the state that we want to seek. 自从看《Dark Wizard》documentary——我完整看了两遍，因为还有 mental-health component，拍得精彩又漂亮——我一直思考 virtuosity。但我喜欢 clutch state，因为听来是应追求的 state。

And the assumption is that high performers are in this relaxed, mellow state, but I'm guessing they spend a significant amount of time there and drilling the really boring stuff to make sure they can get there. Yeah. 人们假设 high performers 很 relaxed、mellow；我猜他们会花大量时间在那里，也反复练极 boring 的 basics，确保能抵达。

嘉宾 Um, Twilight Tharp, who's in her 80s,uh, worldass choreographer, sat in the chair that I'm in and described the daily routine of her worldass dancers. They go through the most basic drills every single day, but every iteration for hours upon hours upon hours before they begin quote unquote practice, right? Before before they try and embrace the the new performance piece. 80 多岁的 world-class choreographer Twyla Tharp，曾坐在这里描述 world-class dancers 的 daily routine：每天都练最 basic drills，每种 iteration 持续数小时，然后才开始所谓 practice，尝试新的 performance piece。

主持人 Mh. but over and over and over often after multiple hours of morning exercise I think we we don't see all of that foundational work and that it needs to be maintained which raises a question do we always need to maintain uh practice the fundamentals 嗯，他们一遍又一遍做，往往此前还有数小时 morning exercise。我们看不到 foundational work 以及它必须被 maintained。这引出问题：总要练 fundamentals 吗？

嘉宾 before I answer your question I think there's there's another useful thing just kind of to remember that relates to all of this from you know in um you know athletes and sports particularly on the training side there's this general idea of thirds right? A third of your sessions,training, um, learning, whatever it is, are going to feel great. You're going to feel really good. You're just going to get stuff, you know, immediately. It's going to just come to you. 回答前，还有一个与 athletes、sports，尤其 training 有关的 useful idea：。三分之一法则。三分之一 sessions——training、learning 或其他——感觉很棒，立刻掌握、一切自然；三分之一普通；三分之一很糟，但仍要出现并完成。

Um, a third will just be average, right? And a third are just going to suck and you just have to show up and get it done. But this is all in the same day or this week across across the week, across months, across years, right? This stuff undulates. And the the the main reason why I say that is because related to this sort of glorification of flow is this idea that these things should just like always come easily to us. 同一天还是一周？横跨 week、months、years，状态会 undulate。之所以提，是因为 glorification of flow 让人觉得事情应总是容易，但这与努力 challenge 自己、build capacity、drive neuroplasticity 完全相反。

But that's completely antithetical to the idea that we have to work hard and challenge ourselves in order to build capacity drive neuroplasticity. 人们追求的感受与真正进步的 grind 存在 tension。

So there's kind of this weird tension between what people are seeking versus what is actually just the part of the the grind of getting better and you know o over time and sometimes it is a grind and that's you know again that's okay doesn't mean you're doing it wrong you maybe it means you're doing it right when you then think about maintaining the fundamentals I think yes but probably it's going to depend on the scenario that that you're that you're thinking about um because sometimes the skill that you're performing, the fundamentals are kind of baked into that in in some way. 有时就是 grind，没关系，不代表做错，也许代表做对。至于 maintain fundamentals，我认为要，但取决于 scenario；有时 performance skill 本身已包含 fundamentals。要看 fundamentals 具体是什么。我想到一项 pianist study，类似 Ericsson 对 violinists 的 studies。

So, it kind kind of depends on what the what the fundamentals really are. Maybe, you know, if it's um so I'm thinking about one specific study that was done in in pianists. Um so this is kind it was kind of related to the Ericson studies in uh in violinists, right? But this time they were looking at uh pianists. And so they had four they had four groups uh older and younger. So the younger was like 20s and 30s, older were 50s and 60s, expert and amateur pianists. 这次有四组：younger（20s、30s）和 older（50s、60s），各自分 expert 与amateur pianists。 experts 来自 German music conservatories。

And so the experts came from um German like music conservatories. Um and then they they looked at um sort of basic skills related to um you know moving the fingers and other things that that you would do playing the piano. And um so they were like very task specific skills related to piano playing. And what they found was that the most important predictor of how well somebody performed at those piano specific skills was not their age, it was how much they practice. 研究测试与 piano playing 相关的 basic、task-specific skills，例如 finger movement。结果发现，预测表现最重要的不是 age，而是 practice amount；reps 帮助维持 basic functions。

So it's just that getting those reps in helps you maintain those sort of like basic functions. And maybe right when you're playing very complex piano pieces, you're encompassing all those fundamentals anyway, right? You don't need to you don't need to like do your you don't need to do your scales every day because some of that stuff is kind of built in. 演奏 complex pieces 时也许已包含 fundamentals，不必每天另练 scales，因为内置其中。但仍会看到people warm up 时练 scales；可能是 warm-up、进入演奏 complex piece 的 routine，也可能帮助维持 fundamentals。

But you will also see people as they warm up say you maybe they will do scales and things cuz that's part of just like you know the warm up maybe part maybe that's routine right this is me getting in the mo in in the mode of you know playing a complex piece but then maybe some of it is just kind of helping to maintain those fundamental skills. 快速休息并感谢 sponsor AG1。 AG1 是含 vitamins、minerals、probiotics，以及prebiotics 和 adaptogens 的 drink。

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主持人 So, now's your opportunity to kill the 10,000 hours. I mean, I know other people have attempted to, but what what does that really boil down to? Is it simply that about 8 hours a day of practice for a dedicated period of time is what leads to rapid plasticity and that's what was measured or is there really a a some sort of rule about time under uh seeking clutch state? 现在你可以终结 10,000-hour rule。它究竟是什么？是每天约八小时、持续一段时间导致 rapid plasticity，还是 clutch-state time 有某种 rule？

The simple answer is what the study showed was that 10,000 hours was the average amount of time that an expert violinist had spent practicing by the time they reached 20 years old. That's what the study showed. They weren't even experts by that point. That was how much they'd practiced, you know, essentially in their youth. So that number of hours doesn't even translate over to true expertise in violinists in this one specific example. 简单答案：研究只显示 expert violinists 到 20 岁时平均累计 practice 10,000 hours。那时他们甚至还不算 experts；只是 youth 期间练习量。所以即使在这个 specific example，hours 也不能等同真正 expertise。

So I don't think there's some fixed number of hours uh required. It is interesting. Other parts of that study kind of looked at the the practice routines of these expert violinists and what they found was that they tended to practice for about two sessions of 60 to 90 minutes a day. And I think that's a pretty good rule, right? 我不认为有 fixed hours。该研究其他部分考察 expert violinists 的 practice routines，发现他们每天通常两次、每次 60 到 90 分钟。

If you're going to do something hard, you're pushing beyond your current skill level, focusing for 60 to 90 minutes, maybe with, you know, a couple of breaks in there, um, a couple of times a day, that's probably about as much as most people can do. And I think that also relates to how we perform on a day-to-day basis in other areas of life, right? 这是不错 rule：做 hard thing、超出 current skill level，focus 60 到 90 分钟，中间可能有几个 breaks，每天两次，大概是多数人的上限。它也对应日常其他 performance。

We kind of expect that we can go to work and we can work really hard for eight hours straight during the day, but like the brain doesn't really work like that. If we're doing hard um, cognitive work, right? you're being you're focused and highly challenged as you might be if you're a um you know a future virtuoso on the violin. You're trying to you know really practice and push yourself. 人们期待上班能连续 hard work 八小时，但 brain 不是这样。 hard cognitive work，需要 focused 且 highly challenged，像未来 violin virtuoso 真正练习、push 自己，只能以 20 到 30 分钟 chunks 做，做几轮并休息。

You can only really do that for you know chunks of 20 to 30 minutes maybe a couple of times of the break right? So like that's why Pomodoro, even though there's no like good studies on the Pomodoro technique, like for those time periods, you know, 25 minutes with a 5-minute break a few times, they do kind of fit into that kind of rhythm that translates over to multiple areas where we might want to use our brains. Pomodoro 虽缺高质量 studies，但 25 分钟加 5 分钟 break，重复几次，确实符合 brain 在多个领域的 rhythm。

Um, and just remember that hard cognitive work and that process of learning can only really happen in those kinds of size of chunks if you want to do them sustainably. 要可持续，hard cognitive work 和 learning 只能在这种 size chunks 中发生。

嘉宾 Yeah. Before I started writing my book, somebody uh who's published several uh very well-received books said, "You can only write for about four solid hours per day 写书前，一位出版多本好评 books 的人说：每天只能 solid writing 约四小时，。

主持人 uh broken up into a couple of sessions." 分成几个 sessions。

嘉宾 I was like, "Come on." I mean, like I'm not trying to boast, but I used to go into the lab and sit down and work on a grant for six hours or something like that. And I started thinking like, was it really six hours? Go in there, see my students and postocs, sit down. Okay,then there's lunch. I need to walk my dog. 我不服，觉得自己以前进 lab 能连续六小时写 grant。后来想，真是六小时吗？先见 students、postdocs，再坐下，然后吃 lunch、遛 dog；有些 late nights，但次日早晨拖着走，因为前晚待太晚。

Yeah. you know, and there were some late nights, but then the next morning I'm kind of dragging because I was in, you know, in my office really late and you you get real honest with yourself real quick and you go, "Oh, okay." In the periods of time where I definitely pushed to the 6 8 10 12 hours of just non-stop work as a deadline approached, there was a compensatory drop in output after after you clicked send. And so I I think 诚实后发现，deadline 前确实有连续 6、8、10、12 小时工作，但点击 send 后 output 会 compensatory drop。所以

主持人 you're right. They're right. It's somewhere between maybe I mean you're saying 60 to 90 minutes and they're saying 4 hours, but not a whole lot more than that for real focused in clutch state work. 你们都对。你说每次 60–90 分钟，他说总计四小时；real focused clutch-state work 上限不高。

嘉宾 Yeah. 对。

主持人 So really digging in and no distractions, no phone, no checking your text messages, just you know. 真正投入，没有 distractions、phone、texts。

嘉宾 Yeah. 对。

主持人 Do you ever give yourself uh forced constraints to get real work done? 你会给自己 forced constraints 来完成 real work 吗？

嘉宾 Not to force it. I will say that um one of the best ways to like truly get deep focused work done is to eliminate distractions, right? That's one of the most important things that you can do. So close the email. I like put my phone in a different room or something because like nowadays your own, you know, close Slack, I have Slack, Teams, my lab and I uh we uh interact on, you know, we message back and forth on WhatsApp. Like there's email. 不会强制。我会说有一件事… …真正完成 deep focused work 的最佳办法之一是 eliminate distractions。关 email，把 phone 放另一 room，关 Slack。

I've got like five or six different ways that people can like constantly try and get my attention, right? So, like eliminating distractions is really important. And again, I return to Gloria Mark's work. She wrote an an excellent book called Attention Span if anybody's like really interested in this. Um, but you get used to a pattern of distraction such that when you're um not actually being distracted, you will distract yourself,right? 我有 Slack、Teams，lab 还用 WhatsApp，加 email，一共有五六种渠道不断争 attention，所以消除 distractions 很重要。再次推荐 Gloria Mark 的书《Attention Span》。

Um, and but you can be trained out of that as well. But so you know that thing where you're trying to do work and you like reach for your phone for no reason. It's because your brain is kind of used to this pattern of you around about now I'm somebody will text me or send me an email and I'll and I'll reach my my phone. So you you go looking for it even if it hasn't happened. 人会习惯 distraction pattern，以至于外界没打扰时也主动 distract yourself。对。但也能重新训练。工作时无缘无故伸手拿 phone，是因为 brain 习惯此时应该有人 text/email，于是即使没有也去寻找。

But again you can train yourself out of that if you if you have periods where you're not getting constantly distracted. So I will eliminate notifications. Um, but at least for me, what I found is that if I if I have a ton of friction in terms of trying to get something done, I will usually step away from it. Um, because there's something in there that just like needs to click or come back before I can like really engage in it. Or if you're at a sticking point. 若有 periods 不被持续打扰，可 train out。我会关闭 notifications。但对我来说，若完成某事有大量 friction，通常会暂时离开，因为里面有个东西需要 click 或等待重新出现，才能真正 engage。

Yeah. Mhm. So if if I'm at a sticking point or it's like if something feels like it's just not coming in the moment, uh I will usually switch over to to to something else, which is also kind of a normal it's a it's it's one of a a possible set of patterns of work, which is that you have two or three projects you're working on on any given time. If one just like isn't quite working, then you can switch over to the other one and come back to it. 遇到 sticking point。对。如果 moment 中就是无法推进，我会 switch 到其他项目。常见 work pattern 是同时有两三个 projects；一个不顺就转另一个，再回来。

And then like the alternative is that when the deadline is so close and uh you know this often happens with a with a grant deadline or you know when I was writing my book and there's a you know a book deadline and you I've got to get this to my editor in um how however many days or hours I I tend to just not need to to eliminate those things because I'll I'll just I'll just focus in like I I I don't feel that kind of draw to be distracted by other things. [吸气] 另一种情况是 deadline 极近，例如 grant 或 book deadline，必须几天或几小时内交给 editor，这时反而不必刻意 eliminate distractions，会自然 focus，不再被其他 things 吸引。

But that usually only happens for relatively short periods of time, right? It's going to be a day or two or hours during a day rather than, you know, extended periods of time. 但这只发生在短期：一两天或一天中的数小时，不会长期持续。

主持人 Are you familiar with this recent study about phone on the table, phone in the bag? We would just remind people that if you're your phone has to be out of the room, even if it's in your bag beneath your chair turned off,you can still focus, but there's a a cost. Your cognitive flexibility, etc. really suffer. So that means that the brain is unconsciously expecting a call. You're sort of waiting for it. 你知道 recent study 比较 phone on table 与 phone in bag 吗？ phone 必须离开 room；即使关机放 chair 下 bag 里，虽然还能 focus，但有 cost，cognitive flexibility 等会受损。这意味着 brain unconsciously 等待 call。

And and the way you describe this attentional break expectation thing um that we get entrained to interruptions is uh really interesting. Um maybe this is why meditation is such a useful tool for improving focus is that it's just a forced no breaks 你描述的 attention-break expectation、被 interruptions entrain，很有意思。也许 meditation 改善 focus，就是强制 no breaks。

嘉宾 yeah thing. Although it's pretty easy to drift in meditation if you are not used to doing 20 minutes of meditation. You sit down to do that you set the timer like your brain can end up way off the trail. there could be some benefit to that as well, right? 对。不过不习惯 20 分钟 meditation 时很容易 drift；设 timer 后 brain 可能远离 trail。

Because there's, you know, without kind of building that in and I and I don't routinely meditate, but um unless you have some parts of your day where actually you're not either putting in information, distracting yourself, thinking about a specific thing, right? You don't necessarily get that time to integrate. Um, you know, that's kind of, you know, the classic is you come up with your best ideas in the shower, right? 这也许也有 benefit，因为如果平时没有建立某些 periods——我不 routinely meditate——真正不输入 information、不 distract、不想 specific thing，就没有 integration time。

because that's actually the time when you don't have your phone on you and you're not watching TV and you're not doing all these other things, you know, at the at the same time. So maybe yes, that's not what meditation is formally for, but it could potentially be beneficial if your mind's going to wander, you know, making new connections, um you know, coming up with new ideas, having that space and time to do it, you know, could potentially be beneficial, too. 经典例子是 shower 中有 best ideas，因为没有 phone、没有TV，也没有同时做其他事。正式 meditation 目的并非 mind wandering，但 wander、形成 new connections/new ideas 的 space/time 也可能 beneficial。

主持人 In these studies, these large scale uh trials, what was the diet intervention? 大型 trials 中 diet intervention 是什么？

Can we distill it down to some things that um everyone should do or ought to consider? 能否提炼成 everyone 应做或考虑的原则？

嘉宾 Most interventions in the sort of um cognitive and psychological space are focused on some version of the Mediterranean diet. Um there's uh the mind diet um Mediterranean intervention to prevent neurogenerative delay. cognitive/psychological space 多数 interventions 聚焦某版 Mediterranean diet。

It came out of the Rush U memory and aging project and it's basically just a version of the um Mediterranean diet kind of focused on um dementia prevention and and the way they initially created it was they looked at foods that people ate more or less of and created a score and those who had a higher score tends to you know had a lower risk of later de dementia. It wasn't an intervention when it was when it was first um developed but that was kind of the version. MIND diet 全称 Mediterranean-DASH Intervention for Neurodegenerative Delay，来自 Rush Memory and Aging Project，基本是面向 dementia prevention 的 Mediterranean diet。

嘉宾 And it it's kind of combination of the Mediterranean diet and the DASH diet which is um like a a anti-hypertension blood pressure treatment type diet. So it's uh you know seafood, vegetables, berries, whole grains, that kind of stuff. Not too much uh saturated fat or animal protein. And so this is very similar to the diet they used in the Smiles trial which was the first randomized control trial in depression that showed significant improvements in in mood symptoms. 最初根据 people foods intake 建 score，higher score 与 later dementia risk 较低相关；起初不是 intervention。它结合 Mediterranean 与 DASH——用于 anti-hypertension/blood-pressure treatment 的 diet：seafood、vegetables、berries、whole grains 等，较少 saturated fat 或 animal protein。

I think the the principles are useful, but there's not necessarily a huge amount of evidence to say that like this is the way that you you should or you have to eat uh to maintain cognitive health. There was actually um a big trial of the mind diet. It was published in the New England Journal of Medicine a couple of years ago and they compared uh the mind diet to standard caloric restriction. Um and actually they saw similar benefits in both in both groups. SMILES trial（首个 depression randomized controlled trial）也用类似 diet，显示 mood symptoms 显著改善。但 principles 有用，不代表有大量 evidence 证明维持 cognitive health 必须这样吃。

There have been big observational studies that have looked at how much their diet looks like a Mediterranean diet. And those whose diets look more like Mediterranean diets, yes, they have a lower risk of dementia. Of course, right, this is observational data, right? So, it's not you can't say it's causal. 一项大型 MIND-diet trial 数年前发表于 NEJM，把 MIND 与 standard caloric restriction 比较，两组 benefit 相似。

But what's interesting in some of these studies, so a big one that came out of the UK bio bank was that they um took out individual uh foods or food components of the Mediterranean diet to see if that changed the relationship between the Mediterranean diet and dementia risk. And there was no food or you know olive oil or food group or you eating more or less meat that changed the relationship between the Mediterranean diet and dementia risk. 大型 observational studies 显示饮食越像 Mediterranean，dementia risk 越低；但 observational 不能证明 causal。 UK Biobank 一项大研究逐个移除 Mediterranean diet 的 individual foods/components，观察 relationship 是否变化；没有任何单一 food、olive oil、food group 或meat intake 会改变 relationship。

So what that tells me is it's much more about whole foods. they're nutrientdense rather than avoiding any you have to eat you have to consume lots of olive oil right or you have to restrict meat because if those things are eaten in the context of all this other stuff it's really that bigger context of diet quality and nutrient density that really matters so the the parts of diet that I think about are the you know there's three so there's energy there's nutrients and then there's overall dietary pattern. 这告诉我关键更可能是 whole foods、nutrient density，而非必须大量 olive oil 或 restrict meat；若都处于整体饮食 context，真正重要的是 overall diet quality/nutrient density。

So, one of the confounding things about that trial I told you about the mind diet versus caloric restriction is you're like, well, the mind diet should win out, right? How does caloric restriction do just as well? And in the kind of average population, we tend to have some issues with metabolic health and have been in a state of chronic energy excess for some period of time. 我从三个方面看 diet：energy、nutrients、overall dietary pattern。 MIND 与 caloric restriction trial 的 puzzle 是：为何后者同样好？ [吸气] 对 average population，metabolic health 常有问题，长期 chronic energy excess。

There's been some very nice studies that have looked at brain aging and brain volume or brain reserve um across different populations. There was um there was uh one group that looked at different um tribes in Bolivia, the Bolivian Chiman who are hunter gatherer group, the Metan who are kind of an intermediate group between sort of the Chiman and like a standard kind of industrialized group and then industrialized humans in the US and Europe. 研究比较不同 populations 的 brain aging、brain volume/reserve，其中一组研究 Bolivia tribes：Bolivian Tsimane（hunter-gatherer）、Moseten（介于 Tsimane 和 standard industrialized group），以及 US/Europe industrialized humans。

And what they found is there's kind of this um bell-shaped curve between energy availability and brain volume. And in general, brain volume, right, the more the better, right, we think. And so if you're chronically calorically restricted, your brain is smaller um because you just don't have the resources to invest in, you know, the structure um and to maintain it. At the other end, you see the same thing. energy availability 与 brain volume 呈 bell-shaped curve；一般认为 brain volume 越多越好。

So if you're chronically in a chronic state of chloric excess, you also tend to have a smaller brain on average. And this is related to metabolic disease um you know and you know potentially and what comes with it um higher levels of inflammation high blood pressure things like that that we know can negatively impact the brain. chronic caloric restriction 会使 brain 更小，因为没有resources 投资并 maintain structure；另一端 chronic caloric excess 同样平均 brain 更小，关联 metabolic disease、inflammation、high blood pressure 等可能 negatively impact brain 的因素。

So the most important thing and I think this is where some of the benefits of caloric restriction happened in that in that trial compared to the mind diet was that you know people's cognition improved just because they decreased their energy intake to a point that was you know more you know was essentially kind of what their brain kind of needed or you know kind of supported their overall physical health which then affects you know cognitive health and and brain volume and and brain function. 这也许解释 caloric restriction 在 trial 中与 MIND 相当：people 减少 energy intake 到更符合 brain 需要、支持 overall physical health 的 level，进而影响 cognitive health、brain volume/function。

So the first thing to do is to make sure that you're eating enough but not too much right and that's very simplistic but like energy is really critical energy availability not too low not too high then the next thing that you need is there is is nutrients we know there are several critical nutrients for uh related to cognitive function and risk of dementia. 第一步是确保吃够但不过量。很 simplistic，但 energy availability 不能过低或过高。其次是 nutrients。

Um the ones that we have the best evidence for are vitamin D, iron, omega-3 fatty acids, uh the B vitamins uh involved and the B vitamins involved in methylation. 与 cognitive function/dementia risk evidence 最好的包括 vitamin D、iron、omega-3 fatty acids，以及参与 methylation 的 B vitamins，

So particularly B12 and folate also potentially B6 and riboflavin although that might depend a little bit more on the individual. Then there are some other nutrients that you know have some pretty good evidence for them. So many of the antioxidant uh polyphenols things that you get from berries, coffee, tea, chocolate, the carotenoids that make things orange, yellow and red. 尤其 B12、folate，也可能包括 B6、riboflavin，但更取决 individual。其他有 evidence 的有 antioxidant polyphenols（berries、coffee、tea、chocolate）、让食物呈 orange/yellow/red 的 carotenoids，如 lutein、zeaxanthin、astaxanthin；后者来自 seafood，使 shrimp/salmon 呈 pink。

Um lutein, zeazanthin, aazanthin if it comes from seafood that's that's what makes shrimp and salmon pink. Um and then you know some other aspects like dietary fiber seems to have you know some some benefits as well. dietary fiber 也似乎有 benefit。

主持人 Not magnesium. Magnesium 呢？

嘉宾 So magnesium is absolutely absolutely in there in there too. Um and in general I think um and the so magnesium uh zinc um then there's some of the structural lipid components things like choline and ethanolamine that you might get from um nuts and seeds or eggs. They have some slightly less you like less evidence. you really when you're looking at um brain changes over time and dementia risk, but they certainly do seem to be related to to cognitive function. 当然也包括。还有 zinc，以及 structural lipid components，如从 nuts/seeds/eggs 获得的 choline、ethanolamine；其 evidence略少，尤其关于 long-term brain change 与 dementia risk，但似乎与 cognitive function 有关。

So, there are some studies that show that those who have lower magnesium intakes tend on average to perform less well on some some cognitive function tests. So, all of those do seem to be important. I have two questions about nutrients and brain health in the short and long term. And they have to do with interactions between nutrients,which at least to my understanding are rarely explored. 有 studies 显示 lower magnesium intake 的人平均在某些 cognitive tests 表现较差。所以都重要。我有两个关于 nutrients 和 short/long-term brain health 的问题，涉及 interactions。

You know, you'll see studies of supplementing omega-3 or having people eat some fatty fish or or less and so on, but rarely in the presence or absence of some other vitamin that, you know, that can potentially impact the same pathways. So there's synergy. There's also, you know, necessity. So that could impact results. The other piece is on what time scale are these nutrients needed and on what time scale are they metabolized? nutrients 之间的 interactions；据我理解这很少被 explored。研究常单独 supplement omega-3、让人多/少吃 fatty fish，却很少考察另一 vitamin 的 presence/absence，而它可能影响同一 pathways。

So maybe to just kind of drill into the second question first. So you know I'm not out here as like the defender of supplements, but I've been taking supplements in various forms and eating whole foods and eating as generally healthily. You know, less so when I was younger, but still pretty healthy and more so as I get older. But here's where my brain goes. 既有 synergy，也有 necessity，会影响 results。另一个问题是这些 nutrients 在什么 time scale被需要和 metabolized？先谈第二个。我不是 supplements 的 defender，但长期以多种形式补充，同时吃 whole foods，年轻时稍差，随年龄更 healthy。

Wait, whole food is great, but let's say dark leafy greens have a bunch of things in them that are fundamentally important for brain and bodily health. Great. And they have fiber, etc. How many times a week am I eating dark leafy greens? Let's say I do Monday, Tuesday, Wednesday. I'm great. But then I'm traveling on, you know, Thursday, Friday. Should I be just supplementing Thursday, Friday? Am I good until the next week? 我的疑问是： whole food 很好；dark leafy greens 含 brain/body health 必需成分和 fiber。若 Monday–Wednesday 吃得好，Thursday–Friday travel，应在后两天 supplement，还是能撑到下周？

I think one of the reasons why eating really well, I think everyone knows what that means, not enough calories, not too many, mostly whole foods, etc., enough vegetables, fruits, and high quality protein and quality fats. I think the reason why supplements still become enticing to me, maybe even necessary, is because you can take them every day very easily. So you can make sure that you're in range and maybe above range. So let's take one of these things. 大家知道健康饮食大致是：calories 不少也不过多、mostly whole foods、足够 vegetables/fruits、high-quality protein/fats。 supplements 仍吸引我，甚至可能 necessary，因为每天服用很容易，可以确保处于 range 或略高。

Okay, omega-3 fatty acids. I I believe that the data are pretty compelling. They can be helpful for health, maybe even brain health. Certainly, I believe that. But let's say the early part of my week is omega-3 rich and the later part of my week is omega-3 poor. Am I good? Versus, you know, spreading it out across the week. it just becomes difficult to eat in a truly healthy way if uh if it's the case that it has to be consistent every 24 hours. So what do we know? 以 omega-3 fatty acids 为例，我认为 data 很 compelling，可能帮助 health 甚至 brain health。若一周前半 omega-3 rich、后半 poor，是否仍足够？还是应 spread across week？若必须每 24 小时一致，真正健康饮食很困难。我们知道什么？

主持人 So again, I think we're often tempted to over complicate this and try and think, oh, you know, I have to hit all these things at this interval and if I can't do that, then I have to supplement. And in reality, we probably have more buffer in the system than than we realize. So, um, omega-3 fats is a really good example. Your adapose tissue, your fat tissue is a depo. 我们常把它 overcomplicate，觉得必须按 interval 达标，否则补充。实际上 system buffer 比想象大。 omega-3 是好例子：adipose/fat tissue 是 depot，储存 excess omega-3。

You know, it kind of stores excess omega-3s. I actually wrote a paper on this with a colleague of mine, Rory Heath, a few years ago. The longchain omega-3s that we have in our fat stores um may help to explain why supplementation does or doesn't work in some of these trials because some people just have more kind of hanging around. And if you eat more than you need on one day, um especially in a state of caloric excess, um that's going to be stored in your fat tissue. 我和 Rory Heath 几年前写 paper；fat stores 的 long-chain omega-3 可能解释为何 supplementation 在 trials 中有时有效、有时无效，因为有人已有更多储备。

And then when uh you're sleeping or when you uh initiate uh lipolysis, the breakdown of fat. So particularly during periods like you're doing exercise, those then get released and they you know the the brain then has access to them. So there's some studies that um show that when you this relates to the form of the omega-3s as well. So many people will tell you that you have to take omega-3s in the phosphoipid form uh which is like a a special it's a special supplement. 某天摄入超过需要，尤其 caloric excess，会存入 fat tissue；sleep 或启动 lipolysis（fat breakdown），特别 exercise 时释放，brain 获得使用。一些 studies 还涉及 omega-3 form。

Um you can get it from krill. Um and the the form is where the the fat is attached to like a a phosphoipid head group just like it would be if it was sitting in in a cell membrane. And there's a specific pathway for those to get into the brain. It's only krill or it's fish oil also. Uh no. So fish tends to be the triglyceride form uh which is you know glycerol and then three fatty acids attached. 很多人说必须 phospholipid form，这是 special supplement，可来自 krill；fat attached to phospholipid head group，像在 cell membrane 中，并有 specific pathway进入 brain。只有 krill，fish oil 呢？ fish 通常是 triglyceride form，即 glycerol 加三条 fatty acids。

When you compare a single dose of phosphoipid versus triglyceride form then more of the phosphoipid form gets into the brain. Some of this, you know, most of this comes from rodent studies, but what's interesting is that if you supplement over several days, it all kind of comes out in the wash because the triglyceride form um cycles through the adapose tissue as a depo and then it gets released and the brain can then use it. 单次比较 phospholipid 与 triglyceride，前者更多进入 brain；多数 evidence 来自 rodent studies。

So, if you're going to take just one day of supplement and you want to get as much of that omega-3 in your brain, yes, you should take the we think we should you should take the phosphoipid form. But the form that comes in seafood, which is primarily the trig triglyceride form, is regulated through the body's fat stores. 但连续 supplement 数天后，差异会消失，因为 triglyceride form 经过 adipose depot 再释放，brain 可以利用。若只补一天并想最大化进入 brain，可能选 phospholipid；seafood 主要 triglyceride form，则由 body fat stores 调节。

So, this is a really long way of me telling you if you eat some fish early in the week, you don't then have to supplement later in the week as long as you got kind of enough. And especially if you've consistently eaten seafood across your entire life because you probably have a bit of a depo. And so what you see in several trials where they've given omega-3s to decrease dementia risk or improve cognitive function. So many studies of like that have been done. 长话短说，一周早些时候吃足够 fish，后几天不必一定 supplement；尤其终身稳定吃 seafood，可能已有 depot。许多 trials 给 omega-3 降低 dementia risk 或改善 cognitive function。

There was actually a very recent one that just came out of of USC where they gave omega-3s for a long period of time. They measured omega-3 levels in the in the CSF, right, in the spinal fluid of these people to show that this the omega-3s were getting into the brain. they didn't see any changes in terms of cognitive function or um brain structure on an MRI scan. So, everybody's like, well, omega-3s don't work. 近期 USC 一项研究长期给予 omega-3，并测 CSF/spinal fluid levels，确认进入 brain，却未见 cognitive function 或 MRI brain structure 改变。

But when you kind of squint at the data and and they didn't quite give me the data that I wanted, but when you look at it, those the people in the trial just didn't seem that omega-3 deficient in the first place. So, right, if this isn't something that you need more of to start with, giving a load more of it isn't going to make that much of a difference, right? And this is the case for all of these different supplements. 大家说 omega-3 无效；但仔细看，虽然没提供我最想要的数据，participants 起初似乎并不omega-3 deficient。若本来不需要，增加很多自然差异不大；所有 supplements 都如此。

So the best advice if you have access to it is to test your levels. Test your vitamin D levels. Test your hemoglobin and iron levels. Test your omega-3 levels. Test your homocyine levels which is as a marker of B vitamin status which we know is a a risk factor for cognitive decline dementia as well. 有条件时最好 test levels：vitamin D、hemoglobin/iron、omega-3、homocysteine；后者是 B-vitamin status marker，也与cognitive decline/dementia risk 有关。 test 显示需要再补充。

So if um if you can test your levels and it shows that you need more and yes there are the the normal ranges that you have on a blood test are not necessarily the same as the risk ranges. So um homoyine is a good example. 但 blood test normal ranges 不一定等于 risk ranges。例如 homocysteine normal range 可能到 15、16；它在缺 methylation-dependent B vitamins 时升高。

A normal range for homocyine which goes up if you need uh some of these methylation dependent B vitamins the normal range might go up to like 15 or 16. But we know that risk is definitely elevated above 13 and is probably elevated above sort of 10 to 11. So what your target range really might be is is probably lower than what the normal range might be. 我们知道 risk 在 13 以上明确升高，也可能在 10–11 以上就升高，所以 target 也许低于 normal range。

But we have very good evidence that if you then supplement when somebody is above that range and you bring that down, you see significant improvements in in cognitive function or slowed cognitive decline. That is particularly the case for omega-3s and B vitamins that lower homocyine. And so this is the interactions that you were talking about earlier and this is the best one that we know of although I'm sure there are many more. 有很好 evidence 表明，高于 range 的人 supplementation 后指标下降，可见 cognitive function 改善或 decline 减慢，尤其 omega-3 与降低 homocysteine 的 B vitamins。这正是 nutrient interaction，也是目前最清楚的一个。

Like I said, there are lots of trials that have given omega-3s or have given u B vitamins to lower homocyine and just haven't seen much of an effect. And everybody goes, "Oh, well, they don't work." But there are now at least three randomized control trials that have shown that omega-3 status and B vitamin status interact and they're dependent on one another. 许多 trials 单给 omega-3 或 B vitamins 没见 effect，就说无效；但至少三个 randomized controlled trials显示 omega-3 与 B-vitamin status 相互依赖：对 elevated homocysteine 者给 B vitamins，若 omega-3 poor，虽然 homocysteine 降了却无 benefit。

So, if you give uh B vitamins to somebody who has elevated homocyine, you bring down their homocyine, but they have poor omega-3 levels, you don't see any benefit. And that's been shown in two trials. It was originally shown in the vittog trial that was run out of the University of Oxford. Um it was then uh replicated in the B proof uh trial.

Then the other side has also been shown there was a in the omega AD trial they showed that supplements with omega-3s didn't result in any benefit if people had elevated homocyine. 两项 trials 显示此点，最初是 Oxford VITACOG trial，随后 B-PROOF replicate。

So this that's just one example and you can imagine like you kind of said there are probably lots of these and if we're not you know going into a study actually looking like well what nutrients does this person need and then supplementing with them um you you you're not going to find any effect like you shouldn't be surprised when there's a when when the study doesn't show anything. potentially the one recent um example of kind of just giving a broadbased kind of set of nutrients with a multivitamin that seemed to work fairly well was the Cosmos study people may have heard of. 另一方向也有： OmegaAD trial 显示，elevated homocysteine 者补 omega-3 无 benefit。 [吸气] 这只是例子；若 study 不先判断 individual 需要哪些 nutrients 再补，找不到 effect 不意外。近期一个 broad-based multivitamin 似乎较有效的例子是 COSMOS study：数千 older adults 随机得到 multivitamin 或 flavonoid supplement。

It was thousands of people of older adults um and they were given either a multivitamin or a a flavonoid supplement.

嘉宾 It's like a sententrum type vitamin. 类似 Centrum 的 vitamin。

Yeah, it was it was Centrum silver, right? The most basic multivitamin, just 100% of the recommended daily allowance, not like no mult no like massive doses of anything. And in that study, those who got the mil got the multivitamin saw, you know, changes in cognitive function that suggested some like some some improvements. And but that was literally just covering the bases, right? No massive doses. The most basic multivitamin. 是 Centrum Silver，最 basic multivitamin，各 nutrients 约 100% recommended daily allowance，没有 massive doses。 multivitamin 组 cognitive function changes 提示有一定 improvement，只是 covering bases。

So in the kind of general population, I think you could say that something like that is probably a reasonable strategy. But what they also showed was that um supplementing with this antioxidant cocoa flavonol was only beneficial in those who tended to have a poor quality diet to start with. Right? So they just weren't getting many of these kind of compounds from their diet. 在 general population，这大概是 reasonable strategy。 study 还显示 antioxidant cocoa flavanol 只对起初 poor-quality diet 者有 benefit，因为 diet 中缺少这些 compounds。

If you're drinking a lot of coffee, eating a lot of berries, seeing a lot of fruits and vegetables, you probably don't need it because you're already getting it. 若大量喝 coffee、吃 berries、fruits/vegetables，可能已足够。

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I I look forward to a day hopefully not long from now where people get their blood work done. They are told and they decide, it's a collaboration after all, which supplements to take. Ideally, those supplements are tailored to them. So, it's not gazillion tablets and capsules and then they can redo their blood work and see whether or not things come into range. And of course, that should be measured against subjective experience of well-being and sleep and all of that. 谢谢澄清。我期待不远的未来，people 做 blood work 后，由专业方告知并协作决定supplements，最好 personalized，不必吞无数 tablets/capsules；之后复测看是否回到 range，并对照 subjective well-being、sleep 等。

That that's not hard to do in today's environment of technology and trackers and blood testing. It's just that uh we're a little bit in the um still in the '9s. uh even just the way that most people talk about supplements, certainly not you, but I think when people hear supplements, they go, "Oh, it's expensive urine." Okay, that's vitamin minerals. Maybe some of that is just getting urinated out, but then there's food replacement supplementation. 以今天 technology、trackers、blood testing 并不难，只是我们仍有点停留在1990s。多数人谈 supplements 会说“只是昂贵 urine”。 vitamins/minerals 一部分会被排出，但还有 food-replacement supplementation，以及为 specific desired effect 的 supplements：缩短入睡时间、增加 slow-wave sleep、focus 等。

And then there's supplements to get a specific desired effect like speed up the transition time to sleep, get more slowwave sleep, um more focus, etc. So it's unfortunate that we don't have good nomenclature like we do in science where where where words are very important so that people can communicate with accuracy. 遗憾的是缺少像 science 那样准确 communication 的 nomenclature。

And I also wonder whether okay if you know one gram of of uh omega-3 uh EPA per day is good um but maybe three is better even though I'm at you know upper range upper reference range. And this is something that like nobody really wants to address because then it sounds like quoteunquote biohacking, but ultimately I think people want to feel good. They want to live longer. No one wants to do anything dangerous. 我还想知道：每天 1 g omega-3 EPA 好，但即使我已在 upper reference range，3 g 会更好吗？没人愿意讨论，因为听起来像所谓 biohacking；但人们终究想 feel good、live longer，也不想危险。

I feel like we're really like in the in like prehistoric times with with how we think how most people think about nutrition and supplementation. I feel like the last 40 years have been spent mostly focusing on what's bad for us. get trans fats, bad, fried foods, bad, eating too much, bad,right? Um, energy over energy toxicity, bad. Um, too much alcohol, bad. Zero is better than any, but you could probably drink a little bit and be fine. 我觉得 nutrition/supplementation 思维仍在 prehistoric times。过去 40 年主要关注什么有害：trans fats、fried foods、eating too much，energy toxicity、too much alcohol 都不好；zero alcohol 更好，但少量可能无事。

Okay, if you're going to take nicotine, don't smoke it or vapor dip it or like we sort of figured it out, right? Don't hit your head. If you do, don't hit it twice, you know? Like, like we've sort of been spending so much time on the don'ts that now I feel like we're in this exciting time of what can you do for one's health? And then there's this divide,right? Just eat whole foods, you'll be fine. And you've actually convinced me that we'll be fine. 若用 nicotine，别 smoke、vape 或 dip。别撞 head，若撞了别连续撞。我们花太多时间谈 don'ts，现在进入“能主动为 health 做什么”的兴奋阶段。但也出现 divide：只吃 whole foods 就够。

The question is, could I be that much better? 你说服我这确实会 fine；问题是能否更好？

嘉宾 This is really interesting to me because there's there's there's two different parts to it potentially, although, you know, they may end up being the same thing. So one is if we're thinking about if we're thinking broadly about improving brain health, cognition at the population level,what's really important is kind of raising the floor. Like what is going to work for everybody and get most of us most of the way there. So like that really is improving food quality. 这里可能有两个部分，最终也许相同。先从 population level 广义改善 brain health/cognition：重要的是 raise the floor，找对所有人有效、让多数人走完大部分路的方法，即 improve food quality 和 access。

Um and then you know access to those foods as well, right?

because that's diff you know that can be very inequitable like can people afford it do they know how to cook it can you know can they access it and then within that I think we also know we have very good evidence for cut offs that predict risk and if you can't get those um nutrients from food I think we should supplement I think I I like to call nutrients like the great leveler of like there's no point in arguing about different diets because your body requires these nutrients and like I don't care where you get them from as long as you get them, right? 后者很 inequitable：能否 afford、会不会 cook、能否 access。同时有很好 evidence 的 cutoffs 能 predict risk；若无法从 food 获取 nutrients，我认为应 supplement。我称 nutrients 是 great leveler：无需争论 diets，body 就需要它们，来源不重要，只要获得；来自 supplements 也可以。

So, if you need to get them from supplements, I think that's fine. That that that should be fine. When you then get kind of to the next level, like how much further can we push function? My answer is I genuinely don't know. Like when you say like, you know, if I put so if I if I test my omega-3 index, right, you said it was the kind of the higher level, maybe it's seven or eight or something like that. All right. If you push it to 12, is that better? 进入下一层，function 还能推多远？我真的不知道。若 omega-3 index 已 7、8，再推到 12 是否更好？不知道。更 complex AI systems、data collection 也许能观察 individual response。

I genuinely I genuinely don't know. like some of these more complex um AI systems, data collection, kind of seeing how you then respond individually as long as you can perform your own sort of like personal experiments, right? As much as you can hold one variable constant, have some meaningful output that you can kind of track over time, see whether it works or not. Can we then aggregate those data to kind of better understand this? I'm excited to see where that goes. 只要能做 personal experiments：尽量 hold one variable constant，跟踪 meaningful output，看是否有效；再 aggregate data，可能更好理解。

I will say that the best evidence we have just says in reality don't be deficient. If you can reach that threshold of not being deficient or insufficient, maybe that's enough. I'm hopeful that that's the case, right? Because then more people will get to that point more more easily, but you know, there's there's a lot that we have to learn there. 我期待进展。但最佳 evidence 现实只说明不要 deficient；达到 not deficient/insufficient threshold，也许就足够。我希望如此，因为更多人更容易达到，但仍有很多未知。

主持人 There was a time in the '9s and 2000s um where people would take stuff and do stuff. I'm not talking about anabolic steroids, although that was happening too. Um, and the whole idea was find things that work, perform really well in one's job or in one's sport, assuming you're not breaking any rules, right? But not tell anyone you were doing them. And then what changed, I think, were two things. 1990s、2000s 时，人们会使用一些东西——不是说 anabolic steroids，虽然也有——理念是找到。有效的方法，在 job/sport 表现好，前提不违规，但不告诉别人。

One is there became a a market value for telling people what one does in order to make money. So people started doing that. And I do believe sharing is good, right? 后来两件事改变：分享自己的做法产生 market value、可以赚钱，所以 people 开始公开；sharing 是好事，但也有。

But also there's this problem that goes with that is that people who sit on the outside of kind of brain and and sports performance or just life just trying to maintain memory and do well in school and be be a busy person and still get sleep and all of that feel like, oh, you know, it's it we're being sold this one thing that's supposed to make all the difference. And I think the thing that really came to came in and changed all of it are the GLPs. 问题：brain/sports-performance 圈外，只想维持 memory、上学表现、忙碌同时 sleep 的人，会感觉被兜售某个 supposedly 改变一切的东西。真正改变局面的是 GLP-1 drugs。

I've never taken a JLP, but I'm just struck by like Americans are now willing to inject themselves. So now it opens up this whole thing about peptides, which you know the major consumers of peptides are not the bro science guys like the gym bros, it's women who look I have female family members, right? 我没用过，但 Americans 现在愿意 injection，于是打开 peptides 世界。主要 consumers 并非 bro-science gym bros，而是 women。

Um who have and they'll tell you me and and there's a long history of people doing and taking things and doing things for their cosmetic appearance and not necessarily sharing it with the world. So, these are the performance-enhancing uh um substances of of a whole different kind, right? And so, how is it that this peptide industry is so intriguing to so many people that Yeah. like jabbing yourself with something that is not FDA approved? 我有 female family members；人们长期为 cosmetic appearance 使用一些东西而不公开。这是另一类 performance-enhancing substances。为什么 peptide industry 如此吸引，连谨慎的人都疯狂注射未经 FDA approved 的东西？

Like people are doing it like crazy, even people who are kind of cautious about what they'll do and put into their body because of this bridge that the JLPs have made. It's so much easier now to just people aren't as needlehobic. 因为 GLP-1 drugs 建立了 bridge，people 不再那么 needle-phobic。

So I think we're entering a time now where people are saying okay you know what the government uh the the the food pyramid the whatever the food quadrants like yeah that's just like if you don't want to die but I want to feel great and there's actually this potential that you and others are sort of offering like you can learn things into your older age you can be uh lean and have great posture into your 60s7s 80s 90s we see examples of this so I think that there's this pull we're getting kind of pulled forward towards this promise 我们正在进入一个时代： government food pyramid 等只是让你不死，但 people 想 feel great；你们展示了可能性：older age 仍能 learn，60s–90s 保持 lean 和 good posture，已有 examples。人们被这 promise 拉向前。

嘉宾 and I don't I think that promise is all about avoiding the the bad stuff. And people say, "Oh yeah, well my grandfather lived to be 102 and he was smoking every great like awesome." But a lot of people don't have those kinds of genetics in their family. They really and genetics play a big role. So I'm kind of editorializing here. I'd love your thoughts on how you sort of sit back and you look at the landscape of things. 我认为 promise 主要是避免坏事。有人说 grandfather 抽烟活到 102，很好，但多数人没有那种 genetics；genetics 很重要。我在 editorialize，想听你怎样看 landscape：eat right、exercise、sleep、socialize 很好，但这些本身就很难。

Um eat right, exercise, get good sleep, socialize is awesome,but that is just that is difficult

主持人 for people that puts people into a clutch state. just trying to do that while managing family and profession and cost of life it you know cost of living that's a lot so I think people do want something that gives them more energy gives them better sleep you know picks up their mood you know and I don't think there's anything wrong with thinking about those things as long as it feeds back to to better behaviors particularly when I think about this kind of this new part of the of the supplement industry and like you said the the you know peptides are just the next they're the next iteration of the pills and potions and things 对 people 而言，兼顾 family、profession、cost of living 就是 clutch state。因此他们想要增加 energy、改善 sleep、提升 mood 的东西；只要反馈到更好 behaviors，我认为这样想没有错。尤其考虑 supplement industry 新部分，peptides 是 pills/potions 的下一 iteration。

嘉宾 to supplements more than drugs because look there's no putting the genie back in the bottle. I don't care what the FDA does and they can mark my words people are going to find their way to get their peptides cuz they love them. 我更把它们看作 supplements 而非 drugs，因为 genie 无法塞回 bottle。不管 FDA 做什么，people 会设法取得 peptides，因为喜欢。

主持人 Mhm. 嗯。[清嗓]

嘉宾 And most people are not playing a drug tested sport. 而且多数人不参加 drug-tested sport。

主持人 Yeah. And there may be adverse events out there, and this isn't a plug for peptides, per se, but where are all these adverse events that are not from botched injections or from really bad black market sources. Where are all the roid rages of peptides? Where are all the like I think you can see way more plastic surgery like like whoa, that looks bad kind of things in it like okay, melanitan's kind of an issue because people can really mess themselves up um there. 对，也许有 adverse events。这不是为 peptides 宣传，但除 botched injections 或 bad black-market sources，adverse events 在哪里？ peptide 的 roid rage 在哪里？反而 plastic surgery 很多 visibly bad results。 Melanotan 确实可能有问题，人会伤害自己。

But where are all the adverse events? Until people start dropping dead from BPC injections, people are going to get and they're going to take their BPC. 但其他 adverse events 呢？在 people 因 BPC injections 大量死亡前，他们仍会取得并使用 BPC。

嘉宾 I'll admit I'm more conservative when you're trying a new supplement or you peptide um I'm going to include peptides in into this, but of course you could it could be a pill or or whatever, right? Some peptides come as pills. I would want some reasonably good evidence of efficacy that this is going to work in humans like me. Um, that's probably not a bar that most of these things are going to hit anytime soon. 我更 conservative。尝试 new supplement 或 peptide——也可能是 pill——我希望有 reasonably good evidence 证明对类似我的 humans 有 efficacy。多数东西短期达不到此 bar。

主持人 No, people don't care. I mean, people who who have no interest in walking into a gym are contacting me like crazy. These are adults who have kids they love, spouses they love. They are not medicine phobic like traditional medicine phobic. And they're like, "Should I be taking low dose? Should I be micro doing or reatite?" I'm like,"Edite's not even released yet." They're like, "Where can I get it?" like, are you kidding me? people 不在乎。完全不想进 gym 的 adults，爱 kids/spouses，也不反 traditional medicine，却疯狂问我：应该 low dose、microdose retatrutide 吗？我说，retatrutide 甚至还没 release。

You know, but it's like it's incredible what's happened in the last few years. 对方问哪里能买。近几年变化惊人。

嘉宾 So, we think about what might what you might think about if if you're going to start to consider one of these. First of all, I would want to see evidence that that it works. The majority of peptides don't have good quality evidence in humans except the GLP ones, right? They're on the market 若考虑使用，第一，我想看 evidence 确认有效。多数 peptides 除 GLP-1 类外缺少 human high-quality evidence；GLP-1 已上市。

主持人 and the growth hormone secrets, but for reasons other than people are taking them. 还有 growth-hormone secretagogues，但批准用途不是 people 当前用法。

嘉宾 Yeah. Yeah. psychopenia um you know other and and with with the most of those growth hormones secret dogs come with a risk of insulin resistance diabetes at high you particularly at higher doses 对，如 sarcopenia 等；多数 growth-hormone secretagogues，尤其 high doses，伴 insulin resistance/diabetes risk。

主持人 yeah they're not the super popular ones I think the super popular ones are besides the GLPS and reat is a GLP and other things but are I would say micro doing of reat and trespatide one category for weight loss um fat loss I would say BPC57 people are taking it without even knowing what the desired effect is 它们不是最 popular。除 GLP-1、retatrutide 也属 GLP 类外，流行的是 micro…… dosing retatrutide、tirzepatide 这一类用于 weight/fat loss。BPC-157 很多人服用却连 desired effect 都不清楚。

嘉宾 recovery is really broad I think it's recovery 太 broad。

主持人 injury repair that's the thesis no human evidence as far as no good human evidence and then there are these other kind of dot dot dot ones I would say um GHK copper for skin thesis 是 injury repair，但据我所知没有 good human evidence。其他还有 GHK-Cu/copper 用于 skin

嘉宾 um appearance those are the three biggies um that seem and the last one in particular with women so I would want evidence that in humans it does what I want it to do most of those if not all of them except for the GOP ones don't don't have that evidence or for the thing or for the thing that you're you're you're trying to get right um but beyond that a question that that you have to ask and and I I like I like this reframing I heard it recently heard it recently from um Jeffrey Bland um which is that if you're going to consider injecting or taking something the first thing you should want to know is is this safe right if you have good safety data then trying it is low risk, right? appearance，这三类最常见，最后一种尤其受 women 欢迎。我会要求 human evidence 证明能实现目标。除 GLP-1 类，绝大多数没有相关 evidence。但还有一个问题，我喜欢Jeffrey Bland 最近的 reframing：考虑 injection 或服用某物，首先应知道是否 safe。若有良好 safety data，尝试就是 low risk；即使无效，至少不危险。

Even if it doesn't work, right? At least, you know, it's not dangerous. And but we don't even have that for most of these. No, we just have the absence of documented adverse effects. Yeah. And in the time course that they've been used because we don't know about long-term use. And so, everybody has their own risk tolerance. Everybody's welcome to do whatever whatever they want, of course. 但多数连这个都没有。只有 absence of documented adverse effects。对，而且只限目前。使用时长，不知 long-term use。每个人 risk tolerance 不同，也有选择自由。

But for me personally, first I would want documented evidence of safety and then you can say, well, I'm willing to try it because, you know, it may or may not do this thing. But you should also have a specific problem that you're trying to solve, right? Otherwise, why would you bother taking it? 对我，先要 documented safety evidence，再决定是否愿试，因为它可能有/无效果；还应有 specific problem，否则为何用？

But it's also the case for the vast majority of supplements that are out there and have been around for long periods of time is first of all, we don't have good evidence of long-term safety at whatever dose that you're taking. And then second of all, we don't know whether it works. For some we do like creatine, omega-3s, magnesium. 多数长期存在的 supplements 也一样：首先缺乏特定 dose 的 long-term safety evidence，其次不知是否有效。有些例外，如 creatine、omega-3、magnesium。

主持人 Yeah. And creatine is actually the best. So like omega-3s, we know that they're, you know, critical nutrient, creatine, I think, is the best example because we know it's very safe, right? So even though this this idea of creatine responders and non-responders, um, you know, maybe it's going to be useful uh to improve or support cognition for some people, not others, may improve physical performance for some people, not others. Creatine 是最好例子。 omega-3 是 critical nutrient；creatine safety 很明确。虽然有 responder/non-responder，可能只改善某些人的 cognition 或 physical performance，但即使给 frail older individuals high doses，也基本没有 side effects。

At least we know that you can give high doses of creatine to frail old older individuals with essentially no side effects, right? We know it's very safe. So then you can try it and see if it benefits you. So creatine is a great example, but there aren't that many others that kind of fit into that category. 因此可以尝试看是否 benefit。 creatine 很好，但类似 category 不多。

嘉宾 Interesting times. 有意思的时代。

主持人 Mhm. Again, I go back to I love the idea of blood testing, tailor tailoring supplementation to the needs of the individual, retesting so people can be really objective about whether their levels are moving in the right or wrong direction. Subjective experience. Um the sleep supplementation thing is kind of interesting because either pe people feel it improves their sleep or it doesn't. Even if it's a placebo effect, which in some cases it could be. 嗯。我仍喜欢 blood testing、按 individual needs tailor supplementation、retest，客观看 levels 方向，再结合 subjective experience。 sleep supplements 很有意思：people 感到改善或没有，即使有时是 placebo；sleep tracking 可看 REM、slow-wave sleep，领域很有趣。

Um with sleep tracking people can see are they getting more REM, are they getting more slowwave sleep? um such a such a fascinating um area. I mean, as you and I both know, there's no plasticity pill,but arousal, alertness, focus seems to be a prerequisite of plasticity,which is why things like caffeine and stimulants and elyroine and all these things that you can find some evidence for them improving plasticity, but it it's very likely to be indirect, right? [清嗓] 我们都知道没有 plasticity pill；但 arousal、alertness、focus 似乎是 plasticity prerequisite。所以 caffeine、stimulants、L-tyrosine 等有 evidence 改善 plasticity，但很可能是 indirect。

It's not that they like make you learn. They set the stage for learning. It seems to always get back to arousal. So, this is what I I want to get back to exercise as as a tool for opening the window for plasticity. Could it be that it's simply a matter of moving your body to get enough adrenaline in your body, norepinephrine in the brain, and maybe some dopamine as well, so that the stage is set for plasticity? 它们不是让你 learn，而是 set the stage；总会回到 arousal。所以回到 exercise 打开 plasticity window：是否只是 movement 让 body adrenaline、brain norepinephrine，可能还有 dopamine 上升，从而准备好 plasticity？

主持人 And it doesn't matter whether you jump rope, do jumping jacks, sprint, or do deadlifts.

It's all about getting your brain into an altered admittedly indogenous chemical altered state of just more arousal and then boom you can go learn is it I mean could it just be that before we get into the exercise there's a an interesting part with the supplements that increase arousal right so the stimulants in particular and I am a big proponent of thinking about or um tracking how somebody feels right I think that how you feel is this kind of ultimate integration of all these inputs and outputs that the brain is kind of bring bringing together, right? 是否无论jump rope、jumping jacks、sprint、deadlift，只要让 brain 进入 endogenous chemical altered、higher-arousal state，就能 learn？进入 exercise 前，先谈增加 arousal 的 supplements，尤其 stimulants。我很支持关注或 track somebody feels。感受是 brain 对 inputs/outputs 的 ultimate integration。

And we know that how you feel, so how an athlete feels is a much better predictor of their performance than their HRV or any of their blood test. athlete 的自我感受比 HRV 或 blood test 更能 predict performance。

嘉宾 What are you asking them? Like you how good do you feel today on one to 10 some some version I feel like I can conquer the world one I feel like exactly on you know and you you can boil it down or I mean you can um spread it out to many more questions. So there's a question there called the rest cue which is all about like how you recovered how recovered you feel, how motivated you feel to train or perform that kind of stuff. 问什么？今天 1–10 感觉多好？某种版本。 1 是很差，10 是能 conquer world。也可拆成更多 questions。有 RestQ questionnaire，问 recovery、training/performance motivation 等；本质就是感觉多好。

But essentially it boils down to how feel how good you feel. If you feel good, you're more likely to perform well. And that works better than the vast majority of data that you like biological physiological data you can collect. There are papers that come out on this every year that essentially show the same thing. That's kind of cool. feel good 更可能 perform well，这一指标胜过绝大多数可收集 biological/physiological data；每年 papers 都显示类似结果。

Yeah,because mindset as my colleague Ali Crumb has focused on so much like mindset can be you can be honest with yourself and you can lie to yourself and tell yourself like okay you got a lousy sleep score but like I feel good. Yeah. 很酷，因为 colleague Alia Crum 大量研究 mindset。人可诚实，也可告诉自己：sleep score 差，但我 feel good。对。

主持人 Or I'm you know maybe sleep scores are like they mean something but today you know right I mean and it can work right I mean in terms of performance. Yeah. And so absolutely right then that gets into like the noibo effect of of how we think about either our sleep data or these other things, right? That that can negatively impact our performance. And we have good good studies um that show that as well. So so I I think that like tracking how you feel is really important. sleep score 也许有意义，但今天仍感觉好，而且 performance 可能真好。这涉及对 sleep data 等的 nocebo effect，会 negatively impact performance，也有 studies 支持。所以 track feeling 很重要。

But when it comes to stimulants in particular, they seem to dissociate how we feel versus how we perform. Right? So there are studies that show that um uh giving people caffeine makes them feel like they're performing better, but they're actually performing worse on certain cognitive tasks. So there's been studies done with like the endback task. 但 stimulants 会 dissociate feeling 与 performance。 studies 显示 caffeine 让人觉得表现更好，却在某些 cognitive tasks 更差。例如复杂 working-memory N-back task，尤其 3-back，需要记三项前是否见过该 letter。

So like very complex uh you know working memory task particularly as you get like to like N3 you're like trying to remember did I see this letter three letters ago, right? In those kinds of complex cognitive tasks, people who take caffeine feel like they're performing better but they're actually performing worse. they're making more errors or they're kind of um you know they're reacting too quickly, they're not really thinking about it. caffeine users 感觉更好，实际 errors 更多或 reaction 太快、没真正思考。其他 stimulants 也有类似 data。

And there are there's similar data from other stimulants too. So there was a paper that came out in science a couple of years ago with uh giving people um methylenadate some of the or some of the other like ADHD medications in people who don't have ADHD. These stimulant medications again show this dissociation between so they feel great. Science 数年前一篇 paper 给 non-ADHD people methylphenidate 等 ADHD medications，同样显示 feeling/performance dissociation：感觉很好。像 cannabis 的反面；人以为有 great ideas，次日觉得很糟。

It's like the the inverse of the cannabis thing where people think they've got all these great ideas and then the next day even they are like oh my goodness this is dreadful. 对，formal studies 让 others objectively rate creativity；cannabis users 觉得更 creative，实际。

Yeah. And that's again been like formalized in studies where where you can do these tests where then other people objectively see how creative were you people taking cannabis felt like they were more creative but actually they weren't. And so the reason why um I say this is that when we're talking about supplements all these other things we're like well I feel much better therefore it must be must be doing something good. 没有。因此谈 supplements 时，“feel better 所以一定有好效果”并不成立；很多 supplements 可制造 feeling/performance dissociation，而一些 endogenous 方法没有。

We know that with many of these supplements you can create this dissociation between how you how you feel and how you perform. whereas some of these endogenous things don't have that effect. So that's why that kind of like endogenous increase in arousal using things like exercise is a much more reliable way to improve performance because you don't kind of get this association between the two. 因此 endogenous arousal increase，如 exercise，更可靠改善 performance，因为不容易出现 dissociation。

So with exercise in particular, we we you know very well that some period of exercise it can be resistance training, aerobic exercise, very brief sprints, increase arousal, improve cognitive function across multiple domains um improve learning um and retrieval, right? So so you're definitely augmenting some of these processes of neuroplasticity. Some of that's going to be related to the catakolamines and other things that get released as you know as you as arousal increases. 一定时期 resistance training、aerobic exercise、brief sprints 都能 increase arousal、改善 multiple cognitive domains、learning 和 retrieval，从而 augment neuroplasticity processes。部分与 arousal 增加时释放的 catecholamines 等有关。 [吸气] 但不同 exercise 对不同 brain parts 有不同 effects。

But we also know that different types of exercise have different effects on different parts of the brain. So yes, I think some of just like the general process of moving your body um and exerting effort definitely increases arousal. Um definitely improves cognitive function, improves learning as long as it's not truly exhaustive exercise. Like anybody who's done some terrible CrossFit wad or, you know, I used to be a rower. 一般 movement/exert effort 确实增加 arousal，改善cognitive function 和 learning，前提不是 truly exhaustive exercise。

We used to do a 2K test on the rowing machine, right? You do a 2K test on a rowing machine, your brain does not work afterwards. It's like a six-minute flat out like V2 max kind of level of exertion. 做过 terrible CrossFit WOD 的人都懂；我以前 row，做 rowing machine 2K test，之后 brain 完全无法工作，因为约六分钟全力 VO2max-level exertion。

嘉宾 Yeah. Thanks. I'm going to interrupt briefly. Thank you for pointing that out because I think that people assume they have an infinite amount of energy and there's crossover and um I certainly have done, you know, extra sets to failure in a great morning workout and then the in the afternoon I'm dragging. If I hold back just a little bit in terms of volume,I find I get a real boost out of training. 谢谢指出，人们常假设。 energy 无限且能 crossover。我在很棒 morning workout 多做 failure sets，afternoon 就拖着；若 volume 稍收一点，training 会带来 boost。

But I do low low volume high intensity, you know, usually two sets per exercise to, you know, two or three exercises per per muscle, like quadriceps being one muscle or something like that. If I do three, it's a small addition, right? The rest of the day I'm kind of dragging. So leaving something in the tank,yeah,does seem worthwhile. not during the sets, but leaving something in the tank in terms of volume really seems to help. 我做 low-volume high-intensity，通常每 exercise 两 sets、每 muscle 两三 exercises。以 quadriceps 为一个 muscle；若加第三项，虽只是小增加，却让 rest of day 疲惫。所以在 volume 上 leave something in tank，对，很值得；不是 sets 内留力，而是 overall volume。

Especially if you want your like to perform hard cognitive work directly afterwards. Sometimes if you're trying to really push sure performance or adaptation, right, is worth digging into that hole. But it really just depends on what you want to be able to do directly afterwards. 尤其若随后要 hard cognitive work。有时要 push performance/adaptation，dig into hole 也值得，但取决于之后要做什么。

主持人 I think student athletes, especially in D1 schools, they really um come to appreciate this. I've had a few of them in my courses over the years and um they really understand when they're pushing very very being pushed very hard in their sport and um they know that they have to sit in the front of the classroom, sit upright, do ex take extra measures to make sure they're not D1 student athletes 很理解。我课程里有几位，sport 中被 push 很 hard，知道必须坐 classroom 前排、upright，并采取 extra measures 防止

嘉宾 dozing off, attention drifting, especially in the age of phones and iPads and and things like that. It's very very difficult. Um, yeah, thank you for for mentioning that because they're just an extreme case of the rest of us. You know, we're told, we're all very busy like, "Oh, you need to exercise. It'll help your brain." And people like, "Well, I exercise and I'm exhausted." You know, that's not helping my brain. Let's get practical here. dozing off、attention drift，phones/iPads 时代尤其困难。谢谢提到，他们只是我们的 extreme case。大家被告知忙也要 exercise、帮助 brain；但有人说我 exercise 后 exhausted，根本没帮 brain。

So, is there any way uh to it's got to be really subjective and uh depend dayto day. Is is there any way to kind of formalize that? like should you train let's say resistance training or running you know should you cap it at an hour should you pull back on the intensity if you have harder cognitive work to do in the afternoon we all want the maximum effect of exercise but we don't want it to undercut our efforts 来点 practical。有没有办法——肯定很 subjective——每天情况都不同。有没有办法把它具体化？比如做抗阻训练或跑步时，是否应把时长控制在一小时内？如果下午有更困难的认知工作，是否应降低强度？我们都想获得运动的最大益处，又不想让它影响之后的工作。

主持人 yeah I think that a lot of it's going to be based on what your current capacity is right as as with everything so if you're you you want to do some you got some you know learning to do you got an exam you want to do some hard cognitive work at, you know, whatever it is, writing a presentation, analyzing data, you uh reading you reading papers, writing your book, then doing some kind of workout that's that's probably below your kind of typical or below what what you would do when you're really sort of pushing pushing the envelope. 我认为这很大程度取决于你当前的能力，和其他事情一样。所以如果你要学习、参加考试，或完成高强度认知任务，比如写演示文稿、分析数据、阅读论文、写书，那么训练强度最好低于你平时的水平，至少低于你真正挑战极限时的水平。

We I think that when you look at meta analyses of exercise and then cognitive function immediately afterwards, the the protocol that has like the best evidence for it is like a 20 to 30 minute jog, right? So like that's the kind of um level of activity that that really seem to sort of like support all those general processes of plasticity and learning. 我认为。从运动后即刻认知功能的 meta-analysis 来看，证据最充分的方案似乎是慢跑 20 到 30 分钟。这样的活动水平确实有助于支持神经可塑性和学习所涉及的各种一般过程。

嘉宾 What do you think is going on? Because it can't be that much arousal. I mean that the amount of catakolamines released from again catakolamines folks being the you know adrenaline, norepinephrine and uh dopamine um generally increased levels of arousal, alertness, uh propensity to move. You just that's that I feel better. People often think about the runner's high and endorphins. The endorphins come from pretty long intense duration effort. 你认为其中发生了什么？这不可能只是因为唤醒程度，因为 catecholamine 的释放量应该不会特别大。这里的 catecholamine 指 adrenaline、norepinephrine 和 dopamine，通常会提高唤醒度、警觉性和活动倾向，也就是那种“我感觉更好了”的状态。人们常说 runner's high 和 endorphin，但 endorphin 通常来自持续较久、强度较高的运动，更像一种飘然感。

They're more of a you're floating kind of like uh you know I think the catakolamines are really the the cocktail of like all right I got a great workout in this morning showered got dressed I'm off to work let's go that's the so 20 or 30 minute jog I don't expect you'd get that much catakolamine release 相比之下，我觉得 catecholamine 更像这样的组合：好，早上完成了一次很棒的训练，洗完澡、穿好衣服，出发上班。所以慢跑 20 或 30 分钟，我预计不会释放太多 catecholamine。

主持人 I mean you'll definitely get some right and like cortisol too right which obviously increases alertness and arousal and can can in the short term make you feel good 但肯定会有一些，也会有 cortisol；它会提高警觉和唤醒程度，短期内也能让人感觉良好。

嘉宾 it's a good thing 这是好事。

主持人 um you you see similar effects of you know short resistance training workouts. Um, I think of it, it's it's probably a little bit of like an area under the curve thing because you see some similar effects of like you go out and you do sixsecond really hard sprints like max effort sprints. You do that a few times with a long break in between, right? That seems to have a similar effect, but you're only working for very short periods with very long rest periods. 短时间抗阻训练也会出现类似效果。我觉得这可能与总暴露量，也就是曲线下面积有关。因为你也会看到类似现象：出去做几次 6 秒的全力冲刺，每次之间充分休息。工作时间很短、休息时间很长，但似乎有相似效果。所以机制大概在这个范围内。

So, it's some it's something in that in that sphere. And I think it's that's probably just it. It's just enough to you just kind of boost catakonamines a little bit, a little bit of cortisol. 我想可能就是这样：catecholamine 稍微升高一点，再加上一点 cortisol。

That's enough to kind of move you up the arousal curve to the point where you're then able to focus and engage a little bit better. And I think yeah, you don't need a huge dump of that um in order to achieve that increase in arousal particularly as it pertains to like learning and then you know cognitive performance in like formal cognitive tests when which is where this is usually done. 这已经足以让你沿唤醒曲线上升到一个更能专注和投入的位置。尤其在学习和正式认知测试中的认知表现方面，并不需要大量释放这些物质，就能提高唤醒程度。如果讨论的是能长期改变认知功能或脑结构的运动类型，付出的努力和运动强度似乎重要得多。

If you're then thinking about the type of exercise that changes cognitive function or brain structure long term,effort uh and intensity do seem to matter a lot more. But those studies have looked less of well how did that how do they feel directly afterwards? Right now you're thinking about what's the kind of stimulus that drives change over time and then intensity matters a lot as well. 不过，这些研究较少考察人们运动结束后立刻感觉如何；它们关注的是怎样的刺激能够推动长期变化，而在这里强度也很重要。最好的例子来自有氧运动，覆盖从 Zone 2 到 Zone 4、Zone 5 冲刺的范围。

So um the the best example um is with aerobic exercise on the kind of uh zone 2 up to kind of zone four five sprint spectrum. So most people who listen to your show are probably familiar with a study where in older adults they had them do uh brisk walking three times a week 40 minutes. Um and when you kind of read the study and and the heart rate uh levels they were trying to attain, it was basically zone 2 work, 40 minutes brisk walking three times a week for a year. 很多听众可能熟悉一项老年人研究：参与者每周快走三次，每次 40 分钟。从论文和目标心率来看，基本就是每周三次、每次 40 分钟的 Zone 2 快走，持续一年。

And they saw significant increases in the volume of the hippocampus uh increases in V2 max fitness, increases in circulating BDNF levels, though circulating BDNF doesn't actually get into the brain, but it's kind of telling you something about probably BDNF that's being produced in the brain. um and improvements in memory. With all of that, [sighs] however, there's a much more recent study that took again older adults and randomized them across three different groups. 研究发现hippocampus 体积显著增加，VO2 max 和体能提高，循环 BDNF 水平上升——虽然循环中的 BDNF 实际上不会进入大脑，但可能间接反映大脑内生成的 BDNF——记忆也有所改善。不过，最近还有一项研究，同样招募了老年人，。

One was like a low inensity group. Another group basically did kind of zone 2 type work on a treadmill three times a week, very sim similar to that previous study that I mentioned. And the third group did um a highintensity interval training intervention, which is the Norwegian 4x4 protocol. So 4 minutes 85 to 95% of maximum heart rate. They had a threeminute rest in their protocol. They did that four times over. 并把他们随机分成三组。一组做低强度运动，另一组每周三次在跑步机上做类似 Zone 2 的运动，与刚才那项研究很相似；第三组进行 high-intensity interval training，采用 Norwegian 4x4 protocol：以最大心率的 85% 到 95% 运动 4 分钟，休息 3 分钟，共做四轮。

嘉宾 That's really hard. Anybody who's done the Norwegian 4x4, if I then say, well, hey, do that three times a week for 6 months. Like that's 这真的很难。任何做过 Norwegian 4x4 的人，如果让他每周做三次、连续 6 个月——

主持人 that was three times a week. 确实是每周三次。

嘉宾 Three times a week for 6 months. That's pretty intense. But what they showed was that that high-intensity interval training group, they improved their fitness just as well as the zone 2 group, interestingly, but they had much better improvements in hippocample function and maintenance of hypocample structure on an MRI scan. And they maintained that benefit for 5 years after the six-month intervention. 每周三次，持续 6 个月，强度很高。但研究显示，HIIT 组的体能提升与 Zone 2 组相当；有意思的是，他们的 hippocampus 功能改善得更明显，hippocampus 结构的维持也更好，。这些变化通过 MRI 扫描观察到。

So they worked really hard um for 6 months, but that that benefit was maintained for a really long period of time. And in several analyses within that study, they basically show that the harder people worked um and the more cortisol they released, the better the benefit. And so this is important because nowadays there's or you know there's several people out there saying, "Oh, don't do high intensity exercise. It releases cortisol. That's stressful. 而且在为期 6 个月的干预结束后，这种益处维持了 5 年。他们努力训练了 6 个月，收益却保持了很长时间。该研究的多项分析基本都显示：训练越努力、释放的 cortisol 越多，获益越大。这一点很重要，因为现在有人说：“不要做高强度运动，它会释放 cortisol，会造成压力，你的身体承受不了。

Your body can't handle it." Right? This study directly shows that working really hard, releasing a lot of cortisol in high-intensity interval training actually improves hippocample structure and function um over over time. So yes, I imagine after they did their workouts, their brain wasn't maybe working at its best cuz that's a hard workout. But over time, this was this really strong stimulus that then resulted in significant improvements. ”但这项研究直接表明，通过 HIIT 努力训练并释放大量 cortisol，长期来看反而改善了 hippocampus 的结构和功能。没错，我能想象他们训练刚结束时大脑未必处于最佳状态，因为那真的很累；但从长期看，这是一种很强的刺激，最终带来了。显著改善。

主持人 Forgive me if you said it and I missed it. Uh what was the form of exercise? Was it rowing or biking or 如果你刚才说过而我漏听了，请原谅。运动形式是什么，是划船还是骑车？

嘉宾 It was on a treadmill. 跑步机。

主持人 Treadmill. 跑步机。

嘉宾 Yeah. 对。

主持人 Uh really interesting. Um and you said it about 85% of max heart rate. 很有意思。你说大约是最大心率的 85%。

嘉宾 Yeah. So that's that's a typical Norwegian 4x4 protocol, but I don't think that's the protocol you have to do. I think it's just this process of highintensity exercise that it releases a whole bunch of myioines and lactate in particular. We know that lactate very easily gets into the brain, generate, you know, stimulates BDNF production as kind of part of that support of neuroplasticity or augmenting recent neuroplastic processes. 对，这是典型的 Norwegian 4x4 protocol，但我不认为非得采用这一具体方案。关键是高强度运动会释放大量 myokine，尤其是 lactate。我们知道 lactate 很容易进入大脑，并刺激 BDNF 生成，从而支持神经可塑性，或增强近期的神经可塑过程。

I think there's something about that just that highintensity work that drives some of those factors that then support structure and function. 我认为高强度运动会促成其中一些因素，继而支持大脑的结构与功能。

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嘉宾 I think if you want it to be sustainable for long periods of time, like I would typically say one day of highintensity work is fine, right? Cuz you probably you want to be doing some resistance training. You I'm doing that three days a week. I do one long slow for me jog of about 60 minutes uh 45 to 60 minutes and then one kind of in moderate kind of maybe more like zone 3 4. So thank you for putting in a a strong um word for cortisol not always being the bad guy. 如果想长期可持续，我通常会说一周一天高强度训练就够了。因为你可能还要做一些抗阻训练。我每周做三天抗阻训练，再做一次对我而言属于长时间、低速的慢跑，大约 45 到 60 分钟；另外还有一次中等强度，可能更接近 Zone 3、Zone 4。谢谢你有力地说明了 cortisol 并不总是。坏东西。

主持人 Um people are so afraid of cortisol. You want your morning cortisol high. It's going to make you sleep better at night. You'll have more energy during the day. It's a It was interesting to me to dive into the literature on cortisol and find that a moderate and int a moderate intensity resistance training session or cardio session probably a little bit easier than the uh 4x4 will triple one's baseline levels of cortisol and like or quadruple it. 人们太害怕 cortisol 了。早晨的 cortisol 应该较高，这会帮助你晚上睡得更好，也让你白天更有精力。我查阅 cortisol 文献时发现，中等强度的抗阻训练或有氧训练——可能比 4x4 稍轻松——大概会让一个人的cortisol 升至基线的三到四倍。

It's transient, but nobody's freaking out about these workouts, but they're afraid to get in a cold shower, which doesn't have nearly the same impact on cortisol or um it's kind of wild how afraid of cortisol people are. People think they're going to get Cushing syndrome. It's been I don't know what the SCOP on cortisol was all about, but you know, you're going to get moon phase, you won't be able to lose abdominal fat. 虽然只是短暂上升，但没有人会因此恐慌；他们却害怕洗冷水澡，而后者对 cortisol 的影响远没那么大。人们对 cortisol 的恐惧有点不可思议，好像会因此患上 Cushing syndrome。我不知道围绕 cortisol 的这一波恐慌从何而来：有人担心出现 moon face，或者腹部脂肪再也减不掉。

I mean there is a a real condition which is you and I know it's a Cushing syndrome where cortisol is is pathologically elevated but come on folks like cortisol goes up cortisol goes down you that but 20 30fold from the morning until night in a healthy individual. So what do you think it is that that people get you know like afraid of cortisol afraid of uh some stress? I mean like your hippocampus obviously in this case their hippocampus got better. 确实存在一种真实疾病，也就是我们都知道的 Cushing syndrome，患者的 cortisol 会病理性升高。但拜托，cortisol 本来就会上升也会下降；健康人从早晨到夜间就可能有二三十倍的变化。那为什么人们如此害怕 cortisol、害怕一点压力？在这个案例中，他们的 hippocampus 明明变得更好了，又没有融化成一摊自己的眼泪。

It's not dissolving into a puddle of its own tears. What What is this? What did What did our predecessors do wrong? [笑声] 这到底是怎么回事？我们的前辈做错了什么？

嘉宾 You know, let's blame it on the parents. What? Because we weren't doing science communication then. What What in the world was the incentive for like demonizing molecules? It's so crazy. So even though his uh frameworks are still potentially very helpful, some of it we can blame on Hans and his like general adaptation response like the the original idea that if you were chronically stressed it would lead to like true exhaustion of all your physiological systems, right? 你知道，怪父母吧。什么？因为当时我们还没做 science communication。到底有什么动力要把某些分子妖魔化？这太疯狂了。 Hans Selye 的一些框架可能仍然很有帮助，但这件事有一部分也许要归因于他提出的 general adaptation response，也就是最初认为如果人长期处于压力中，所有生理系统最终都会真正耗竭，因为那是 general adaptation response 的最后阶段。

Because that was the final phase of his general adaptation response.

主持人 People have conflated acute stresses versus chronic stresses. And yes, we know chronic stress be they psychological, physical, increase allatic load, increase metabolic disease, inflammation, blood sugar dysregulation, insulin resistance significantly associated with heart disease, dementia, all these kinds of things, right? So we so we know that these chronic stresses are can be really detrimental to our health. 人们把急性压力和慢性压力混为一谈。我们确实知道，长期的心理或身体压力会增加 allostatic load，并增加代谢疾病、炎症、血糖调节异常和 insulin resistance；它还与心脏病、dementia 等诸多问题显著相关。这些我们都知道，慢性压力确实可能严重损害健康。

But we've kind of conflated that like any stress is bad because chronic stress is bad. But the way that I think about it or I try and talk about it is that actually the stress response and this is as kind of Sier originally described it is stress drives adaptation. He called it general adaptation syndrome or the general adaptation response because what stress is is your body acknowledging that you need to respond to some external stimulus, right? 但因为慢性压力有害，我们把它误解成任何压力都不好。我理解并尝试表达的是：stress response 实际上会推动 adaptation，正如 Selye 最初所描述的那样。他称之为 general adaptation syndrome，或者general adaptation response，因为所谓压力，就是身体意识到自己需要对某种外部刺激作出反应。

And so stress diverts resources so that you can then adapt to that stimulus. Be they physical, cognitive, neurological, right? A stressor diverts glucose to the immune system, right, in in an infection so that it functions better. You can eliminate the infection. 压力会调配资源，让你能够适应这种刺激，无论它是身体、认知还是神经层面的。

And so yeah, if you took somebody and you like look you measure their cortile levels after a workout, it actually looks very similar to how it would look if you just broken your arm or if you were like really sick, right? 比如感染时，stressor 会把 glucose 调配给 immune system，使其运作得更好，从而消除感染。如果测量一个人锻炼后的 cortisol 水平，它看起来可能与刚摔断手臂或病得很重时很相似。

This is the body adapting to a stimulus and like everything we've talked about here you know physical training driving neuroplasticity that requires adaptation and so some of that core stress response is involved in that the release of cacodium as you talked about in the brain right those are stress related molecules that are driving adaptation so that your body can deal with the stressor better in the future and we also know actually that there's some where there's some evidence for the uh cross stressor adaptation particularly with exercise, right? 这就是身体在适应刺激。我们在这里讨论的一切，包括身体训练促进 neuroplasticity，都需要 adaptation，因此核心的 stress response 会参与其中。就像你说的，大脑会释放 catecholamine；这些与压力相关的分子会推动 adaptation，让身体未来能更好地应对 stressor。

So, if you exercise regularly, you are better at dealing with other stresses like psychological stresses. You won't you're more robust to stresses. Your mood or your cognitive function doesn't dip as much when you're when you're then psychologically stressed. So, stress is actually really important because it's the fundamental driver of adaptation. 我们也知道，有一些证据支持 cross-stressor adaptation，尤其是通过运动。也就是说，经常运动会让你更能应对其他压力，比如心理压力；你的抗压能力更强，在心理压力下，情绪或认知功能下降得不会那么多。

But because we've kind of, you know, we know that chronic stress is bad if if you never get a chance and that's because you never get a chance to adapt. You never get a chance to downregulate. you never get a chance to respond because it's just continuous. But right intermittent exposure to these stressors is really important. And Selia also talked about the idea of hypo stress, right? 因此，压力非常重要，因为它是 adaptation 的根本驱动力。但我们知道慢性压力有害；如果你始终没有机会适应、没有机会下调或作出恢复性反应，因为压力一直持续，那当然会有问题。间歇性接触这些 stressor 却很重要。 Selye 还谈到 hypostress 的概念，也就是压力不足。

Not having enough stress because then you can't you don't adapt, you don't build function and response. So we just need to think about them very differently because that those acute stresses are incredibly important for driving adaptation. 没有足够压力，你就无法适应，也无法建立相应的功能和反应。因此，我们需要以非常不同的方式理解急性与慢性压力，因为急性压力对于推动 adaptation 至关重要。

嘉宾 Way I think of it is pick your stressor. You can either be exercise or it can be psychological stress. If you take it in the form of exercise, you probably have less in the form of psychological stress. It's obvious not not completely true at a one for one, but I think uh as you pointed out, we and all organisms thrive on some degree of stress. I think if people are getting enough good sleep at night, 我的理解是：选择你的 stressor。它可以是运动，也可以是心理压力。如果用运动的形式承受压力，你可能会少承受一些心理压力。这显然不是严格的一比一关系，但我认为，正如你指出的，我们和所有生物都需要一定程度的压力才能良好运作。我认为，只要人们晚上获得足够的优质睡眠——

主持人 yeah, sleep is the 对，睡眠是关键。

嘉宾 I don't want to say there's no limit to the amount of stress they can absorb, but when it starts to erode your sleep, that's perhaps when things need to be, you know, adjusted. 我不想说人能承受的压力没有上限，但如果压力开始侵蚀睡眠，可能就需要调整了。

主持人 Resistance training. Um, is there a particular protocol for resistance training that opens the opportunity for plasticity better than others that is supported in the literature? Again, two different windows say of of action. So, there's that that acute kind of arousal and this would be um, you know, you you go in the gym, you do a couple of sets, you're not maxing out. 关于抗阻训练，有没有哪种得到文献支持的 protocol，比其他方案更能为 plasticity 创造条件？同样，要区分两个不同的作用时间窗口。第一个是急性的唤醒效应：你去健身房做几组，但不做到极限。

Um, you know, it's it's probably going to be your fairly typical couple of sets of uh 8 to 12 reps, kind of 80% of of max, something like that. You do compound movements. So, most studies use machines, right? Um, so maybe do a leg press and a chest press and a lat pull down, shoulder press, multi- joint movements, usually with machines. 大概就是很常见的方案，每个动作做几组、每组 8 到 12 次，负荷约为最大能力的 80%，类似这样。做 compound movement。多数研究使用器械，比如 leg press、chest press、lat pulldown、shoulder press，都是多关节动作，通常用器械完成。

And again, if that takes 20 to 30 minutes, that kind of shows some similar effects to that like 20 to 30 minute jog that I talked about in terms of some acute bumps in in in cognitive function probably through through arousal the mild activation of those arousal pathways actually quite similarly though I mean probably um slightly higher intensity will also be beneficial as long as you're able to uh recover over time like that that that recovery is is critical just like I was just saying in terms of any kind of adaptation. [哼声]如果训练用时 20 到 30 分钟，在认知功能的急性提升方面，效果与刚才说的 20 到 30 分钟慢跑相似，很可能是通过唤醒以及对相关。唤醒通路的轻度激活。与此类似，只要之后能够充分恢复，稍高一点的强度可能也有益；正如我刚才谈到各种 adaptation 时所说，恢复至关重要。

Um there are several studies of resistance training looking at cognitive function and uh brain structure over time. I say several, it's like three or four in older adults and they typically do two or three times a week, five to six exercises, three sets of 8 to 12 reps. Very very similar. Um, so those multi- joint machines in in the gym that anybody can do and they're in any gym. 有几项研究考察了抗阻训练对长期认知功能和脑结构的影响。这里说“几项”，其实也就是三四项老年人研究。典型方案是每周两到三次、五到六个动作、每个动作 3 组、每组 8 到 12 次，彼此非常相似。使用的是健身房常见、任何人都能操作的多关节器械。

嘉宾 Presses, pull-ups, rowing, pull downs, leg press, leg press, 推、pull-up、划船、pulldown、leg press——

主持人 hamstring curls. Exactly. Okay. 还有 hamstring curl。没错。

嘉宾 Yeah. 对。

主持人 And what you tend to see is that if you do that for at least 6 months, so the studies go on for like 6 to 12 months, you see significant um changes in the structure of the white matter of the brain and with that improvements in executive function. You want to remind people what white matter is just for for the for the newbies. 通常会看到，如果你。至少坚持 6 个月——研究通常持续 6 到 12 个月——大脑 white matter 的结构会发生显著变化，同时 executive function 也会改善。能不能给刚接触这个概念的听众解释一下什么是 white matter？

嘉宾 Very broadly, you have white matter and gray matter in your brain. In the human brain, white matter makes up approximately 60% um more than um most other species, any other species. And so like the wrinkly outer part of your brain, the cortex, that's gray matter. You also have more gray matter deep inside the brain. In between that is the white matter, which is where you have uh the myelin sheaths on your axons. 粗略来说，大脑由 white matter 和 gray matter 构成。在人脑中，white matter 大约占 60%，比例高于其他任何物种。大脑外层有褶皱的 cortex 属于 gray matter，大脑深部也有 gray matter。

That's what allows those uh nerves to conduct information really quickly. Whereas aerobic exercise on that kind of intensity spectrum we just talked about seems to particularly benefit the gray matter which includes the hippocampus. Resistance training seems to particularly benefit the white matter. Um and so you see improvements in a white matter structure which and and changes in white matter structure with age are one of the best predictors of cognitive decline with age. 两者之间是 white matter，其中包含包裹 axon 的 myelin sheath，使神经能够快速传导信息。我们刚才谈到的、覆盖不同强度的有氧运动，似乎尤其有益于 gray matter，包括 hippocampus；而抗阻训练似乎尤其有益于 white matter。研究观察到 white matter 结构改善，而 white matter 结构随年龄发生的变化，是预测老年认知下降最好的指标之一。

Interestingly, like outside of other things you see in terms of neuropathology, amaloid tow etc. That loss of white matter structure and function is you know closely tied to cognitive decline over time. So you see improvements in structure and function of the white matter and potentially improvements in something that we call Y matter lesions which tend to happen um around areas of poor blood flow uh within the Y matter of the brain. 有意思的是，即使不考虑 amyloid、tau 等其他 neuropathology，white matter 结构与功能的丧失本身也与认知功能随时间下降密切相关。因此，研究看到 white matter 的结构和功能改善，也可能看到所谓 white matter lesion 的改善。

Um and with that improvements in executive function. So um uh aerobic exercise is gray matter and memory and resistance training is um white matter and more sort of executive type decision-m processing speed type functions. You know we talked about uh lactate and some of these other things that might increase uh um uh BDNF with the aerobic training in resistance training. 这类病灶往往出现在大脑 white matter 内血流不足的区域，同时 executive function 也有所改善。因此可以粗略概括为：有氧运动对应 gray matter 和记忆，抗阻训练对应 white matter，以及更偏 executive function、决策和 processing speed 的能力。

The I I think the primary mediator of that or one of them is IGF-1 which is in particularly increased with resistance training. We know that IGF-1 is really critical to the development of white matter uh you know right you know in the womb and then as a baby and it seems to be also really important for for white matter structure then throughout um the lifespan. 我们刚才谈过 lactate 等因素可能在有氧训练中提高 BDNF。对抗阻训练而言，我认为主要介质之一是 IGF-1，抗阻训练尤其会提高它。

So resistance training is a really great way to then create these boosts of of IGF-1. So that's probably that's that's probably part of of of why we see that difference. But that that's why you need to do both though they may have similar kind of acute effects in terms of cognitive function. they seem to be having very different effects in terms of the structure and function of the brain long term. 我们知道 IGF-1 对 white matter 的发育非常关键，从胎儿期到婴儿期都是如此；而且它似乎终生都对维持 white matter 结构很重要。所以抗阻训练是促使 IGF-1 短暂升高的很好方式，这可能部分解释了为什么我们会看到这种差异。但也正因为如此，两种运动都需要做。它们对认知功能可能有相似的急性作用，长期来看，对脑结构与功能的影响却似乎非常不同。

主持人 I so appreciate that you're basically telling us that different forms of exercise impact different critical aspects of brain structure and function. So, resistance training, white matter,cardio, gray matter, broadly speaking, and many different molecules, IGF-1, BDNF, lactate, and on and on. Just for uh uh what how do you say in in Britain? 我很感谢你告诉我们，不同运动形式会影响大脑结构和功能中不同的关键部分。也就是抗阻训练对应 white matter，有氧运动大体对应 gray matter，同时还涉及 IGF-1、BDNF、lactate 等许多分子。只是为了消遣一下——英国怎么说来着？

Well, it's not kicks, they use a different word, but for kicks and giggles, I'll just tell you there were sort of two running jokes in the field of neuroscience when I was coming up, which was if you desperately need a thesis, fortunately, this was not the position I found myself in. uh if you desperately need a thesis and like it's not going well, study the effect of pretty much any compound on REM sleep because it will reduce REM sleep. 不是“for kicks”，他们用另一个说法——我讲讲自己刚进入 neuroscience 领域时的两个常见笑话。其中一个是：如果你急需一个 thesis 题目——幸好我当时没有落到这一步——如果你的thesis 实在进展不顺，就研究几乎任何化合物对 REM sleep 的影响，因为它多半都会减少 REM sleep。

There are very few things that increase REM sleep. Very, very few except sleep deprivation and then REM rebound. 能增加 REM sleep 的东西非常少，真的少之又少，除了 sleep deprivation 后出现的 REM rebound。

嘉宾 Likewise, there was a review published by a guy named Jeff Lickman and Josh Sains who were in a different field. So, they did a kind of cocky thing, but they back then they were like like they're good guys. Um I know them both. 同样，Jeff Lichtman 和 Josh Sanes 曾发表一篇 review；他们来自另一个领域，所以这件事做得有点张扬，不过他们都是很好的人，我也认识两位。

Um but they published this review about long-term potentiation where they said they did a review of the literature and they said basically you can throw any molecule on a couple of neurons and do the protocol for long-term potentiation and you get an enhancement of long-term potentiation. Now that wasn't completely true. 他们发表了一篇关于 long-term potentiation 的 review，说查阅文献后基本发现：随便把一种分子加到几枚 neuron 上，再做 long-term potentiation protocol，往往都能增强 long-term potentiation。

The reason I'm raising this is that there's this theme right like it's um there are certain processes like processes that are not that hard to disrupt like REM sleep. you just kind of tweak the system a little bit, you see a deficit, small or large deficit. 当然，这并不完全准确。我提起它是因为这里有一个共同主题：某些过程并不难被扰乱，比如 REM sleep。你只要稍微调整系统，就会看到或小或大的缺损。

And then things like long-term potentiation, which is thought to underly a lot of forms of learning and memory in a dish with some neurons or maybe even an animal, you can knock something out or overexpress something and whoop, you get more or less long-term potentiation. It's not that hard to tilt the scale on it. But in reality, the human body has tons of molecules that it deploys. 而 long-term potentiation 被认为是多种学习和记忆的基础。在培养皿的一些 neuron 上，甚至在动物中，敲除或过表达某个东西，long-term potentiation 就可能增多或减少；让天平发生倾斜并不难。但现实中，人体会同时调动大量分子。

And it now to me makes perfect sense why plasticity which of course is the the foundation of learning sort of one in the same uh in many ways is brought about by resistance training and by cardiovascular training because they're both motor. 因此我现在觉得完全合理的是，plasticity 本来就是学习的基础，两者在很多方面几乎是一回事；而抗阻训练和心血管训练都能促成 plasticity，因为二者都涉及运动控制。

主持人 Yeah. 对。

嘉宾 Just like crossword puzzles certain plasticity effect 就像 crossword puzzle 也会产生一定的 plasticity 效应。

主持人 maybe less than you know dance where there's a number of different things social inputs balance inputs and on and on. 也许不如舞蹈，因为舞蹈还同时包含社交输入、平衡输入等多种成分。

So whereas 2 3 years ago I would have said all right are we really talking about exercise opening plasticity that's always seemed like mice running on wheels and you get a few extra neurons you get a nature paper like I love that work don't get me wrong but it turns out to not be that meaningful in terms of new neuron production isn't that doesn't seem to be that meaningful for human uh memory and and offsetting cognitive decline. 因此，如果在两三年前，我可能会说：运动真的能打开 plasticity 吗？那时总觉得这类研究就是小鼠在滚轮上跑，然后多长出几个 neuron，再发一篇 Nature。别误会，我很喜欢那些工作，但事实证明，至少在新 neuron 生成这一点上，它对人类记忆和延缓认知衰退似乎没有那么重要。

So, but now I have a completely different view of exercise based on your work, based on the studies that you're describing because it's like, yeah, these are the big guns in terms of deploying lots of molecules that without question are interacting with one another. So, I no longer think about exercise as like okay well like it's just increasing vessel growth, you're getting more metabolic health, so then the brain gets better. 不过现在，基于你的工作和你所描述的这些研究，我对运动有了完全不同的看法，因为运动像是在动用重武器：它会调动大量分子，而这些分子毫无疑问还会彼此作用。所以我不再把运动仅仅理解成：它增加血管生长、改善 metabolic health，于是大脑顺带变好。

Um I now think about resistance training and cardio and their various forms as you point out 4x4 etc as like the real plasticity uh triggers. 我现在把抗阻训练、有氧运动及其不同形式——包括你提到的 4x4 等——视为真正的。 plasticity trigger。

嘉宾 So that that was a long-winded way of saying thank you to you and your colleagues who've been doing this and thinking about things like clutch states and and molecules that shift plasticity because I love reductionist single molecule manipulations. I think they're very important in a certain context, but uh for a while it was like gosh, everything opens plasticity and everything disrupts REM sleep and like when are we going to get to this stuff? 我绕了很久，其实就是想感谢你和你的同事一直在研究这些问题，思考 clutch state 以及改变 plasticity 的分子。我很喜欢 reductionist 的单分子操作，它在特定情境中非常重要；但有一阵子我总觉得：怎么所有东西都能打开 plasticity，所有东西又都能破坏 REM sleep，我们什么时候才能看到真正有用的结论？

主持人 Anyway, Alzheimer's, Parkinson's, nobody wants these neurodeenerative conditions. What is the current thinking about the factors that make one susceptible to Alzheimer's? I'm beginning to think that it's not just one, but that there's a p genetic predisposition issue that maybe you could touch on. And what can we do besides the things that we're already talking about today um to best reduce the chance of um accelerated cognitive decline or full-blown Alzheimer's? 回到 Alzheimer's 和 Parkinson's：没人希望患上这些 neurodegenerative disease。目前对于哪些因素会使人更容易患 Alzheimer's，有什么看法？我开始觉得原因不止一个，其中还有 genetic predisposition，也许你可以谈谈。除了今天已经讨论过的事情，我们还能做什么，才能尽量降低认知加速下降或发展为完整 Alzheimer's disease 的概率？

嘉宾 First, we talk about dementia um which is essentially the end stage of cognitive decline. there's some trajectory of decline that happens from your peak to that point um where ideally we'd intervene much sooner but right now you know we don't really do much until dementia is diagnosed. 先说 dementia，它本质上是认知下降的终末阶段。从认知能力峰值到那个阶段之间存在一条下降轨迹；理想情况下，我们应更早干预，但目前往往要等到 dementia 确诊后才真正行动。这和 diabetes 很相似：确诊之前通常不会做太多事。

It's but it's very similar like we don't do very much until diabetes is diagnosed. you know, ideally we can we can act much earlier in that trajectory and that's increasingly being accepted in the neuroscience and neurology communities that actually we could potentially change that trajectory or at least decrease risk. 理想情况下，我们可以在这条轨迹上更早采取行动。 neuroscience 和 neurology 界也越来越接受这样的观点：我们也许能够改变认知下降轨迹，至少可以降低风险。

And so within dementia there are as an umbrella term which is essentially the loss of cognitive function such that you can't look after yourself on a day-to-day basis. You can't do the day you sort of the the basic activities of daily living. Alzheimer's disease is the most common. It makes up about 60 to 80% of cases of dementia. Um the next most common is vascular dementia. Dementia 是一个 umbrella term，本质上指认知功能丧失到无法在日常生活中照顾自己、无法完成基本 daily living activity 的程度。 Alzheimer's disease 最常见，约占 dementia 病例的 60% 到 80%；其次是 vascular dementia。

Although vascular dementia and Alzheimer's disease overlap a ton like the vast majority of people who have Alzheimer's disease also have some element of pathology or changes in the blood vessels in the brain which is what you get with vascular dementia. 不过两者高度重叠，绝大多数 Alzheimer's disease 患者的大脑血管也存在某种病理或变化，这正是 vascular dementia 中会出现的情况。然后还有 dementia with Lewy bodies、frontotemporal dementia，以及可能与 Parkinson's disease 相关的 dementia。

And then there's also dementia with Louis bodies um uh front to temporal dementia and then uh dementia related to Parkinson's potentially although that overlaps a lot with um Louisibody dementia and and dementia and Parkinson's may just be may actually mostly be Louis body dementia but [gasps] we've gotten to a point now where it's generally accepted that potentially half of cases of dementia are preventable and I think the majority of that falls into those first two buckets Alzheimer's and vascular dementia although metabolic disease and other risk factors for Alzheimer's disease also increase the risk of Parkinson's disease and and those other dementias as well. 后者与 Lewy body dementia 重叠很多；Parkinson's 中的 dementia 也许很大程度上其实就是 Lewy body dementia。现在普遍接受的一种说法是，可能有一半 dementia 病例可以预防；我认为其中大部分落在前两个类别，也就是 Alzheimer's 和 vascular dementia。不过 metabolic disease 和其他 Alzheimer's 风险因素，也会增加 Parkinson's disease 及其他 dementia 的风险。

When you then think about Alzheimer's disease specifically, there's there's one small slice of Alzheimer's which is like monogenic dominant mutations that you have in either most of them happen either in the precinylan genes pin one and two or the amaloid precursor protein gene. They make up at this point less than 5% maybe as little as 1% of Alzheimer's disease. So, we're kind of we set those to the side a little bit. 具体看 Alzheimer's disease，其中有一小部分由单基因显性突变造成，多数涉及 presenilin gene PSEN1、PSEN2，或 amyloid precursor protein gene。这类病例目前不到 5%，甚至可能低至 1%。

The vast majority of Alzheimer's disease is what we would call late onset Alzheimer's disease, although it's happening actually earlier and earlier in in some populations. Yes, there's a genetic component. Um, your APOE gene is your probably your most common uh risk gene. It's also associated there's also polygenic risk. 所以可以暂时把它们单独放在一边。绝大多数属于所谓 late-onset Alzheimer's disease，尽管它在某些人群中实际发生得越来越早。遗传因素确实存在，APOE 大概是最常见的风险基因；另外还有 polygenic risk，成千上万个 gene 都可能让 Alzheimer's disease 风险稍高或稍低。

So thousands of genes can give you a little bit more a little bit less risk of of of Alzheimer's disease, [gasps] but it's much more related to lifestyle and the environment than say that that kind of early onset monogenic Alzheimer's disease. 不过相较于 early-onset monogenic Alzheimer's disease，这类病例与生活方式和环境的关系大得多。

And the the kind of the best accepted um review of all of this um is is run by the Lancet Comm Commission on Dementia Prevention uh overseen by professor Jill Livingston and their most the most recent version of this suggested there were 14 risk factors who between them accounted for about 45% of uh de dementia risk or dementia cases and that are modifiable. 这方面最被广泛接受的综述来自 Lancet Commission on Dementia Prevention，由 Professor Gill Livingston 领导。

So early life education, high blood pressure, diabetes, hearing loss, vision loss, brain trauma, um high uh high cholesterol, they recently recently added 他们最近的版本提出 14 项可改变的风险因素，合计可解释大约 45% 的 dementia 风险或病例，包括早年教育、高血压、diabetes、听力损失、视力损失、脑外伤、高 cholesterol；他们最近还加入了——。

主持人 high LDL, 高 LDL。

嘉宾 high LDL cholesterol, low physical activity. So this is all related to the things we've already talked about,right? Maintaining good physical health, maintaining uh maintaining inputs, getting inputs in the first place, right? Education is is uh is critical. Um 高 LDL cholesterol，以及身体活动不足。这些都与我们刚才讨论的内容有关：维持良好身体健康，也要维持输入、首先获得输入，而教育非常关键。

主持人 and hearing loss, as I recall, was an important one, right? in reference to to inputs like you don't want sensory input degraded. 我记得听力损失也是一个重要因素，对吧？这和输入有关，因为不希望感官输入退化。

嘉宾 Absolutely. So hearing loss, vision loss, um social isolation. Um they didn't uh it was quite so two things they didn't include um that were fairly controversial and were sort of debated. Letters were written to the editor and all that kind of stuff as happens in in academia uh related to so they didn't include sleep loss or sleep deprivation as a risk factor for dementia even though the evidence particularly if you're 没错，包括听力损失、视力损失和社会隔离。有两项因素他们没有纳入，因此引起了相当大的争议和讨论，也有人给编辑写信，academia 里经常如此。其中一项是 sleep loss 或 sleep deprivation。尽管有相关证据，尤其如果你——

主持人 didn't look at it or didn't include it. 是他们没研究，还是没纳入？

嘉宾 They didn't include it. So, like they talked about it, but they felt that the level of evidence wasn't high enough, though it was probably as high as some of the other things that they included. 没纳入。他们讨论了这项因素，但认为证据等级还不够高，尽管可能与某些被纳入因素的证据强度差不多。

主持人 It's a tricky one. I I don't want to take us on too much of a tangent, but having looked at these data a lot, I do think that people need to get enough sleep, but some people, like myself, do fine on 6 and 1 half or 7 hours, and other people can do fine on only seven or eight or nine. 这确实棘手。我不想离题太远，但仔细看过很多相关数据后，我确实认为人需要睡够。不过有些人，比如我，每晚睡 6.5 或 7 小时也能状态良好；另一些人则需要 7、8 或 9 小时。

嘉宾 Very few people are a-okay all the time on just four to five hours for prolonged periods of time. But what but when we say not a-ok okay what tends to happen with shift work or people that are chronically sleepd deprived is most of the other things you're talking about get worse LDL goes up stress levels goes up diabetes go so it's 极少有人能长期每晚只睡 4 到 5 小时而一直完全没问题。但所谓“有问题”，在 shift work 或长期 sleep deprivation 的人身上，往往表现为你提到的其他指标一起恶化：LDL 升高、压力水平上升、diabetes 风险加重。所以——

主持人 it's like uh I can understand why they might not have included it but it seems so foundational to me that it does seem kind of a shame part of it is related to how they analyze the data so we can we can we can get to that but I mean in reality when you look at the data on sleep loss and dementia risk The cut off is really around 6 hours. So if you're consistently sleeping fewer than 6 hours, that's where risk starts to increase. 我能理解他们为什么。可能没把睡眠纳入，但它在我看来太基础了，遗漏它还是很遗憾。这部分与他们分析数据的方法有关，之后可以展开。不过从 sleep loss 与 dementia 风险的数据看，分界点确实大约是 6 小时：如果长期每晚睡不到 6 小时，风险就开始升高。

So that that kind of sounds Yeah, that sounds about right. Cuz it's the I think it's the LA it's the lack of those last two cycles where that are REM enriched. 听起来合理。我想可能是因为少了最后两个以 REM 为主的 sleep cycle。

嘉宾 Yeah. 对。

主持人 You know, cuz in the beginning of the night, you get your growth hormone surge, you get a lot of deep sleep, assuming you're, you know, doing things right during the day and and then it's those last, you know, 290 minuteish cycles that you glean most of your REM. 夜晚前半段会有 growth hormone surge，也有大量 deep sleep——前提是白天的行为适当。大部分 REM 则来自最后大约两个、各 90 分钟的 cycle。

嘉宾 Yeah. And if you're not getting those night in and night out and night in night out, like sooner or later, you're going to have issues. 对。如果日复一日都缺少这些阶段，迟早会出问题。

主持人 Yeah. So, so sleep was one. Then the other one was was nutrient status. So, they didn't talk about omega-3s, B vitamins, which we do actually have some some quite high quality interventional and observational kind of epidemiological data for. So, there was kind of some discussion as whether those things should have been included. 所以睡眠是一项。另一项是 nutrient status。他们也没有讨论 omega-3、B vitamin，而实际上我们有一些质量相当高的 intervention data 和 observational epidemiological data。

Other analyses that looked at those suggested that they potentially contribute a significant of the amount of the population attributable risk of dementia. 因此，学界讨论过是否应把这些因素纳入。

So all that to say that their 45% estimate could be quite conservative if we consider some of the other things there there are some other studies that suggest that the maybe as many as or as much as 70% of dementias may be preventable but then you have to start including things related to socioeconomic status and deprivation and other societal factors that we know have a massive impact as well. So that's less modifiable like on the individual level, right? 另一些包含这些因素的分析提示，它们可能对 population-attributable risk of dementia 贡献显著。也就是说，如果把其他因素也考虑进去，45% 这个估计可能相当保守。还有一些研究甚至认为多达 70% 的 dementia 也许可以预防，但这时就必须把 socioeconomic status、deprivation 以及其他社会因素纳入，而我们知道这些因素影响巨大。

It really would require mod like changes at the societal level which is kind of harder to do. 它们在个人层面较难改变，需要社会层面的变革，因此更难做到。

嘉宾 Could I ask you a question? It's going to be a very controversial one, but 我能问个可能非常有争议的问题吗？

主持人 um 可以。

嘉宾 there are people arguing there are very smart people I should say arguing that the shingles vaccine is lowering rates of dementia significantly. I haven't looked at those data closely yet. I plan to, but it certainly is intriguing given the data that herpes viruses of various sorts have been correlated with uh Alzheimer's. This comes off the back of three or four very large natural experiments that have been done in in various countries. 有些非常聪明的人主张，shingles vaccine 正显著降低 dementia 的发生率。我还没仔细研究这些数据，打算去看；不过考虑到多种 herpesvirus 都被发现与 Alzheimer's 相关，这件事确实很耐人寻味。这个说法来自在不同国家进行的三四项大型 natural experiment。

And really how you interpret these data is going to depend a little bit on your kind of risk tolerance and like how you what you think should be done in terms of the le level of evidence required to to intervene. So, I'll describe the studies in a second, but some people are definitely saying, you know, if you want to say that um the shingles vaccine decreases dementia risk, you have have to have a clinical trial that's adequately powered to show that. 如何解读这些数据，部分取决于你的风险容忍度，以及你认为采取干预需要什么等级的证据。我马上介绍这些研究。有些人明确认为，如果要声称 shingles vaccine 能降低 dementia 风险，就必须开展统计功效足够的 clinical trial。

And there is a trial like that being planned currently. 目前确实正在规划这样一项 trial。

主持人 So, the the studies that have happened so far, uh there was one in the UK, in Wales, uh one in Australia, uh and one in Canada. And in each of those countries, what happened was that on a single date, a huge trunch of people became eligible to get the shingles vaccine. Whereas if they were born one day earlier, they weren't eligible. 到目前为止，相关研究包括英国 Wales 的一项、Australia 的一项和 Canada 的一项。在每个国家，当时都出现了这样的情况：某个特定日期起，一大批人突然符合接种 shingles vaccine 的资格，而早出生一天的人反而没有资格。

So you get what you call like a natural experiment where from one day to the next, those people shouldn't be that different otherwise. and and they showed that, you know, rates of other diseases weren't that different. Rates of uptake of other, you know, health care and other vaccines weren't wasn't that different, but there different there was a big shift in the uptake of of the shingles vaccine. 于是形成所谓 natural experiment：日期前后的人群按理说在其他方面不应有明显差异。研究也显示，两组其他疾病的发生率没有明显不同，使用其他医疗服务和接种其他疫苗的比例也没有明显差异，但 shingles vaccine 的。

And so what they essentially consistently showed across all those different populations was that those who got the shingles vaccine um or were eligible to have the shingles vaccine, depending on whether they had access to the data on whether people got it or not, had a had decreased risk of dementia. And that was consistently seen across those three groups. 接种率却发生了很大变化。这些不同人群中的研究一致显示，接种了 shingles vaccine 的人，或者符合接种资格的人——取决于研究是否能取得实际接种数据——dementia 风险较低。三个群体都观察到这一结果。这些研究使用的都是较旧的 shingles vaccine Zostavax，Zostavax 是 live attenuated vaccine。

All those three trials used an older version of the shingles vaccine called zostifax zostifax which was a live attenuated vaccine.

There's now a newer version uh called Shingri which is a recombinant vaccine and there was a study done in the US that um compared people who switched from you know there was a similar switch from Zustvax to Shingri and and saw that Shingrix was associated with with a lower risk of dementia compared to Zustvax although both were associated with a lower risk than none. 现在有一种较新的 recombinant vaccine，叫 Shingrix。美国一项研究利用从 Zostavax 切换至 Shingrix 的类似情况进行比较，发现相较于 Zostavax，Shingrix 与更低的 dementia 风险相关；不过两者相较于完全不接种，都与更低风险相关。

When you look at some of these trials um or studies because they're not trials, people have made the a very fair comment which is that when you look at the trajectory of dementia over time, you look at something called a Kaplan Meyer curve. So it's like a survival curve. 查看其中一些研究时——它们不是 trial——有人提出了一个完全合理的问题：观察 dementia 随时间发生的轨迹时，会使用 Kaplan–Meier curve，类似 survival curve。

So like um every time somebody gets a case of dementia like the line goes up and you look at the trajectory of the two lines those who got you know got the uh vaccine or not they diverge very early which kind of says that oh it only takes a couple of months to kind of see this difference in dementia risk which you which you wouldn't really expect based on like the natural course of dementia takes years to happen. So um this is very common in these kinds of studies. 每出现一例 dementia，曲线就变化；比较接种和未接种两组的轨迹会发现，两条线很早就开始分离。这似乎意味着只需几个月就能看出 dementia 风险差异，但考虑到 dementia 的自然进程通常要持续多年，这并不符合预期。

Um and it it's it's due to residual confounding. So there's like something inherently different about the populations that may be driving some of this different. Right? They they were going to get less dementia anyway. And so maybe the shingles vaccine isn't having that big of an effect. 这类研究中很常见的问题是 residual confounding，也就是两个人群可能存在某种内在差异，并由此造成部分结果：他们原本就可能较少患 dementia，因此 shingles vaccine 也许并没有。

But I would say that having looked at all those trials and all those data, I'm fairly, you know, I'm convinced enough that um there's there's a signal there. there should be a randomized control trial. That's that's happening. But there's a number of reasons why this might be the case. One, uh it obviously we know reduces cases of shingles. Shingles can be very painful. It can, you know, can uh change how people interact with the world. You stay at home. You don't feel good. 那么大的作用。不过，在看过所有这些研究和数据后，我认为其中确实存在一个信号，至少足以让我信服。应该开展 randomized controlled trial，目前也正在推进。之所以可能存在这种关联，有几个原因。第一，我们知道 vaccine 显然会减少 shingles 病例；shingles 可能非常疼痛，也可能改变人们与外界互动的方式。

You're in a lot of pain for a long period of time. That can be that can go for you many months. It's rare for it to last many months, but it can can last a long time. Um then you know there's they've hypothesized in some of those papers that the magnitude of the reduction of dementia risk didn't map perfectly onto the reduction in uh in cases of shingles. Right? There had to be something else going on as well. 你待在家里，感觉不好，长时间处于疼痛中。这种状态可能持续数月，虽不常见，但确实可能持续很久。有些论文提出，dementia 风险下降的幅度与 shingles 病例减少的幅度并不完全对应，也就是说，可能还有其他机制在发挥作用。

They've suggested that it may be um due to like an imunom modulatory effect. It may be because you're also suppressing other viruses like herpes simplex virus that we know uh may also be associated with certain cases of dementia Alzheimer's. Um and the reason you one of the arguments for the imunom modulatory effect is because not in all the studies but in most of the studies there's a slightly bigger signal in women than there is in men. Um and it may be that that sort of um 他们认为，这可能来自 immunomodulatory effect；也可能是因为同时抑制了 herpes simplex virus 等其他病毒，而我们知道这类病毒也许与某些 dementia 或 Alzheimer's 病例有关。支持 immunomodulatory effect 的一个理由是：虽然并非每项研究都如此，但多数研究中女性的信号都略强于男性。

嘉宾 meaning it's more effective in 也就是对女性更有效？

主持人 more effective in women than it was in men. And we should mention that the shingles virus lives on neurons. 对，女性中的效果比男性更明显。还应提到，引发 shingles 的病毒会潜伏在 neuron 上。

嘉宾 Yes. 是的。

主持人 Yeah. The herpes viruses tend to live on neurons that and they hang out on neurons which is why people who you know get herpes one infections will get a cold sore at a particular location that will come back because it's living on the trigeminal nerve. This just you know uh I think people don't often understand that viruses can you know harbor in in particular cell types. Herpesvirus 往往潜伏在 neuron 上，所以感染 HSV-1 的人会在特定位置反复出现 cold sore，因为病毒潜伏在 trigeminal nerve 上。我觉得人们常常不了解病毒可以潜伏在特定 cell type 中。

Yeah. And uh so the logical link between herpes viruses and and uh dementia risk is you know it's not I mean that that alone is not a causal relationship but it but it makes sense mechanistically. Yeah. And a fundamental feature of herpes viruses is they generally don't kill the neuron. They can but that's why they stay alive. These viruses are very smart. 对。因此，herpesvirus 与 dementia 风险之间存在一种符合逻辑的联系。仅凭这一点当然不能证明 causality，但在机制上说得通。对。 Herpesvirus 的一个基本特征是，它们通常不会杀死 neuron；它们也可能做到，但一般不会。正因为如此，病毒才能继续存活。这些病毒很聪明。

嘉宾 They know how to get infect their host but not kill their host which is what really smart viruses do. 它们懂得感染 host 却不杀死 host，聪明的病毒都是这样。

主持人 Yeah. So what age are people getting the shingles vaccine? 人们一般多大年龄接种 shingles vaccine？

嘉宾 The study is actually quite late. It's like people in their 807s and 80s. 这些研究中的年龄其实很大，参与者大约七八十岁。

主持人 Oh wow. 哇。

嘉宾 Yeah. 对。

主持人 Okay. 好。

嘉宾 So again, um it would be very fair to argue that getting it much earlier we don't have any evidence for because you know in reality in these particularly in these the studies um like the UK this is done in the national healthcare system. it was you know for the the highest risk older you know older adults and so getting it in your like 50s or you know mid-50s which is u sort of the guidelines in the US that yes to reduce shingles absolutely but it doesn't map onto the dementia risk um age that was seen in seen in these studies a final piece of this that I think is important and kind of goes beyond just the shingles vaccine is that if you want to maintain function over long periods of time, one of the best things you can do is minimize your chances of getting really sick. 所以，有人完全可以合理地指出：我们没有证据说明更早接种也有同样效果，因为这些研究，尤其是。英国的研究，是在 National Health Service 中面向高风险老年人开展的。美国 guideline 建议五十多岁接种；若目的是减少 shingles，当然有依据，但这个年龄与上述研究中观察 dementia 风险的年龄并不对应。最后还有一点，我认为很重要，而且不只适用于 shingles vaccine：如果想长期维持功能，最有效的事情之一就是尽量减少患重病的概率。

There have been sever several studies, one was the adult changes in thought study done at the univers University of Washington in Seattle primarily. Um this a similar thing was shown in the Rush memory and aging project. But basically, when you look at the same individual over time and you measure their cognitive function every few years, which these studies did, cognitive function doesn't just decline sort of linearly or steadily with age. 有几项研究支持这一点，包括主要由 Seattle 的 University of Washington 开展的 Adult Changes in Thought Study，以及得出相似结果的 Rush Memory and Aging Project。

It goes down, you know, a little bit on average, but the biggest decreases sort of happen stepwise after periods of significant illness. Um and so like in the adult changes in the thought study, those who'd been um you know sick in between, you know, had a major illness in between uh have be having their cognition retested, they had a step change down and those who were hospitalized that that step change down was even bigger. 它们都是对同一个人长期追踪，每隔几年测量一次认知功能。结果发现，认知功能并不是随着年龄线性、平稳下降。平均而言会逐渐下降一点，但最大幅度的下降往往发生在严重疾病之后，呈阶梯式变化。在 Adult Changes in Thought Study 中，如果参与者在两次认知复测之间患过重大疾病，下一次测试就会出现阶梯式下降；如果还住过院，下降幅度更大。

So you could talk about, you know, how people maybe could have changed things in order to recover some of that function afterwards. I think that would have been possible if you'd, you know, thought thought about how you might intervene. But a major I think it it's a reason to say if I can do as much as I can to minimize the chance that I get really sick because what happens then is I'm I'm at home. I'm not receiving any stimuli any inputs. I'm not moving. I'm not eating well. 当然可以讨论患病后怎样干预，帮助恢复部分功能；如果认真设计干预，我认为这是可能的。但更重要的一点是，应尽可能减少患重病的概率。因为重病时，人会待在家里，接收不到刺激或输入，停止活动，也吃不好；感染本身当然还有各种负面影响。

Obviously there's the all the downsides of the infection itself. um then you know if I can avoid that as much as possible then over time that that that could lead to you know greater benefits right change change change the overall trajectory so I think that's one reason why some of these vaccinations could be beneficial is just you're minimizing the time you spend really sick as you're older which we've seen is results in these sort of like step changes down in cognitive function fascinating I realized that we could and probably should do an entire podcast about traumatic brain brain injury and concussion. 如果能尽量避免这种状态，长期累积下来就可能带来更大收益，改变总体轨迹。因此我认为，这就是某些 vaccine 可能有益的一个原因：它们减少了人在年老后处于重病状态的时间，而我们已经看到，重病会造成认知功能这种阶梯式下降。很有意思。我意识到，我们可以、也应该专门做一期关于 traumatic brain injury 和 concussion 的节目。

嘉宾 But as a teaser for that, um, 不过先做个预告：

主持人 are there anything that people should do and or take in the immediate aftermath of a head hit? Now, I'm not talking about uh hopefully people are getting checked out for brain bleeds and things like that. So, I'm I'm talking about moderate concussion. Someone got their quote unquote bell rung. uh they slipped and fell. Uh they got clipped in soccer practice. Um their kids a little dizzy. 头部受到撞击后，有没有什么应该立刻做或服用的东西？当然，我不是说发生 brain bleed 等情况时不去检查。我指的是 moderate concussion：有人感觉被“震懵了”，滑倒摔了一跤，在足球训练中被撞到，孩子有点头晕。

Not of course somebody young or old is vomiting or you know not able to sleep or real issues. I mean everyone should probably be checked out in in the first case but I get asked this question all the time. Is there anything that people can take to kind of get over mild concussion or moderate concussion? The evidence base on this is a little shaky, but I think for most things it kind of fits into this idea of positive asymmetry, right? Low risk, high potential for benefit. 这里当然不包括无论年轻人还是老人出现呕吐、无法睡觉或其他真正严重问题；原则上，第一种情况每个人也都应接受检查。但我总被问到：有没有什么东西能帮助人从 mild 或 moderate concussion 中恢复？这方面的证据基础不算扎实，不过多数做法符合 positive asymmetry：低风险，潜在收益高。

And there have been lots of you there have been randomized control trials to kind of look at some of these things. So we a couple years ago we published a paper looking at different nutritional supplements after concussion that you know we have some reasonably good evidence for. So, um, yes, you should be seen by a doctor. You should get whatever scans and, you know, immediate medical care that you need. Absolutely. Right. 而且确实有不少 randomized controlled trial 考察过其中一些方法。几年前，我们发表过一篇论文，评估 concussion 后的不同 nutritional supplement，其中一些有相对不错的证据。但首先，人应该就医，接受所需的 scan 和紧急医疗照护，这一点毋庸置疑。

That's we're assuming all of that is done or will be done. 下面的讨论假设这些已经完成或将会完成。

嘉宾 Yeah. 对。

主持人 Immediately, there are a couple of things that I think we know um from sort of um animal studies that translate fairly well onto onto humans, but also some you maybe some observational studies in humans. But, a couple of things are important. So one is temp temperature management temperature regulation. There have been this is what my PhD was actually in hypothermia after acute brain injury 在受伤后立刻，有几件事来自 animal study，似乎能较好地转化到人体，也有一些 human observational study 的支持。首先重要的是 temperature management 和 temperature regulation。我 PhD 研究的其实就是 acute brain injury 后的 hypothermia。

嘉宾 hyperothermia. Hyperthermia？

主持人 Hypothermia. Yeah. So cooling down. Hypothermia，也就是降温。

嘉宾 Although I did do some studies where we you know heat it up and that makes things worse. So this kind of pertains to imagine brain doesn't like to get too hot. That's essentially what I'm about to say. So there have been lots of studies where they've done cooling hypothermia in people after traumatic brain injuries and concussions hasn't really shown much of an effect. What seems to be important is preventing hyperothermia. 不过我也做过一些升温实验，结果会变得更糟。所以可以想象，大脑不喜欢过热。这正是我要说的。很多研究曾在 traumatic brain injury 或 concussion 后对患者实施 cooling、诱导 hypothermia，但没有显示出太大效果。真正重要的似乎是防止 hyperthermia。

So um one of the effects of cooling somebody down is that they don't get hot. So that's probably something that's really important. So often concussions happen in a heat stressed environment. You're on a football pitch. It's August in Alabama. It's 40°, right? Get inside, get cool as quickly as you can because there are there are studies that and that doesn't mean you have to get an ice bath. Just don't be really hot. 给人降温的一个结果，就是避免体温过高。这可能非常重要。 Concussion 经常发生在炎热环境中，比如八月在 Alabama 的 football field 上，气温 40°C。此时应尽快进入室内、降温；这不意味着必须泡 ice bath，只是不要持续过热。

If you get a fever, which you might might do after a more significant injury, you know, Tylenol or something like that to help maintain thermmorreulation will be really important. The next is uh blood sugar regulation. So, we know that after a significant brain injury, you have increases in in blood sugar that's associated with worse outcomes. Some of it's like what's caused, what's consequence, is the injury driving the blood sugar, is the blood sugar driving the injury. 如果更严重的损伤后发烧，可以在医疗指导下用 Tylenol 之类帮助维持 thermoregulation，这会非常重要。其次是 blood sugar regulation。严重 brain injury 后 blood sugar 会升高，并与较差 outcome 相关，但这里难以区分因果：是损伤推高血糖，还是血糖加重损伤？

I think an easy thing to just say is I would avoid any super sugary refined carbohydrates that might just sort of you know uh kind of pile on for one of a better word, right? What about alcohol? So alcohol um I would avoid as well mainly because it impairs sleep and we know that sleep is going to be critical to recovery. Some people would say something similar about caffeine acutely after injury because it's a it's a stimulant. 一个简单做法是避免高糖的 refined carbohydrate，免得进一步增加负担。那 alcohol 呢？我也会避免 alcohol，主要因为它会损害睡眠，而睡眠对恢复至关重要。有人会建议损伤后短期内也避免 caffeine，因为它是 stimulant。

Um, one thing that the reason why hyperothermia or getting too hot makes the injury worse is because it um, you know, simply speaking increases the gap between energy requirements and energy production. So like one of the hallmarks of these acute brain injuries is a deficit in energy production with you know mitochondrial failure or mitochondrial dysfunction. 过热会加重损伤，其中一个原因，简单说就是它扩大了能量需求与能量生成之间的差距。因为这类acute brain injury 的标志之一，就是 mitochondrial failure 或 dysfunction 导致能量生成不足。如果过热或刺激大脑，就等于在 neuron 无法生成足够能量时要求更多能量。

And so if you get too hot or you stimulate the brain, you're asking for more energy when the when your neurons can't produce it and that is a trigger that kind of deficit in energy production is a trigger for cell death and neuroinflammation and some of these other processes that then may happen. So avoid alcohol, avoid caffeine. Both of those potentially related to improving sleep. 这种能量缺口会触发 cell death、neuroinflammation 以及随后可能发生的其他过程。因此应避免 alcohol 和 caffeine；两者也都可能与改善睡眠有关。然后，有一些相对合理的证据支持 concussion 后立刻使用 creatine。

Then uh things that we have some you know reasonable evidence for um immediately after concussion are creatine. At what dosage? The best trial was actually done um in a p like pediatric group although very broad. It was like one year old to 18 years old. Um but they gave point4 gram per kilo per day. So wa. Yeah. So it's it's a pretty it's it's like double a traditional loading dose if you're a 100 kilo person. 剂量是多少？最好的一项 trial 其实在 pediatric group 中进行，年龄跨度很大，从 1 岁到 18 岁；使用剂量是每天每公斤体重 0.4 克。哇。对，量很大，大概是传统 loading dose 的两倍。

But like if you're 7 if you're 70 kilos um you know 155 lbs or something like that then that's 28 g of creatine. So like it's a lot but not 如果体重 100 公斤尤其如此；若体重 70 公斤，也就是大约 155 磅，每天就是 28 克 creatine，确实很多。

主持人 trips to the bathroom could be expected but you just spread it out across the day right. 可能会频繁跑厕所，但把它分散到全天服用就行，对吧？

嘉宾 Yes. So well one thing I'll say about that is um the most recent meta analyses show that you actually don't get is actually quite rare to get more GI side effects uh with creatine compared to placebo. Some of it is probably related to the quality of the supplement. So poor quality creatine supplements have more adulterance that may cause some of those GI side effects. Some of it is can be due to high um um you can saturate the creatine transporters. It doesn't get absorbed. 对。不过我要补充，最新 meta-analysis 显示，与 placebo 相比，creatine 导致更多 GI side effect 的情况其实相当少见。部分问题可能与 supplement 品质有关。低质量 creatine supplement 含有更多 adulterant，可能造成某些 GI side effect。

Water gets drawn into the gut that can that can then write cause diarrhea or something. Um but some of the GI issues that people experience are probably due to poor quality products that they're taking. 还有一种情况是高剂量使 creatine transporter 饱和，creatine 无法被吸收，水被拉进肠道，从而可能导致 diarrhea 等症状。不过，人们经历的一些 GI 问题可能源于所用产品质量差。

For the non uh head injured individual, is there any reason to go back to the old loading protocols of taking 20 grams per day, putting it in a little bit of grape juice or something else to spike blood sugar for this very reason that it could um augment the the passage of creatine into your cells as opposed to drawing water into the gut? In the '9s, we would take five grams of creatine four times a day in an ounce or two of pure grape juice. 对于没有 head injury 的人，有没有理由回到过去那种 loading protocol：每天摄入 20 克 creatine，配少量 grape juice 或其他能提高 blood sugar 的饮料，借此促进 creatine 进入 cell，而不是把水拉进肠道？上世纪 90 年代，我们会每天四次服用 5 克 creatine，每次配一两盎司纯 grape juice。

Yeah. Um, and you draw a lot of water into your muscle cells. You put on, you know, it varies, but for me, anywhere from 5 to 8 pounds of, it's water weight, but it's mostly in the muscles. It's not insignificant. Translates to big strength increases. I don't take nearly that much now. I just do the 10 grams per day. But is there any reason to go back to those traditional loading? 对。这样会把大量水带进 muscle cell，体重会增加，因人而异；对我来说大约是 5 到 8 磅。那是 water weight，但主要在 muscle 中，幅度并不小，也会带来明显的 strength increase。我现在没吃那么多，只是每天 10 克。但有必要回到传统 loading protocol 吗？

主持人 So, if you're just like long like long-term creatine supplementation, pro probably not. um in this kind of setting I think a a you know the the evidence is for a loading style protocol right so for most people it might be 20 to 30 grams of of creatine spread spread across the day you know for if anybody's just like taking creatine for other reasons you know this is a standard dosing protocol I think is fine 如果只是长期补充 creatine，可能没有必要。不过在 concussion 这种情境下，现有证据支持 loading-style protocol。多数人可能是每天 20 到 30 克 creatine，分散到全天服用。至于因为其他原因服用 creatine 的人，我认为标准剂量方案就可以。

嘉宾 I thought you were going to tell me I could get it to work that way 我还以为你会告诉我，。这样能让它更有效。

主持人 so so like the the some of the studies that use traditional like creatine monohydrate and look at creatine levels in the brain they did use is a loading protocol for for a week and then you see significant increases in brain creatine. But you creatine having other effects on the brain, you know, potentially improving mood, improving uh memory and in older adults. Um some of those benefits happen at just like a traditional creatine doses. 有些使用传统 creatine monohydrate 并测量 brain creatine 水平的研究，确实先采用一周 loading protocol，随后能看到 brain creatine 显著升高。但 creatine 对大脑的其他潜在作用，比如改善 mood，以及改善老年人的 memory，有些在传统剂量下也会出现。

So you don't need to take massive doses, you know, take load loading doses. You can actually see some benefits of like 5 to 10 grams. So that's a creatine. So magnesium, so 400 milligrams once or twice a day. There've been some trials that shown um 因此不需要服用很大的 loading dose；每天 5 到10 克就可能看到一些益处。 Creatine 先说到这里。再说 magnesium，每次 400 mg、每天一到两次；有些 trial 显示——

嘉宾 what form 哪种形式？

主持人 those studies actually use magnesium oxide. surprisingly. Um, but I would probably use magnesium glycinate. Um, the it's very bioavailable. Um, athletes usually need a bit more glycine anyway, but any bioavailable form will will be fine than omega-3 fatty acids. 那些研究实际上使用 magnesium oxide，很令人意外。不过我可能会选择 magnesium glycinate，它的 bioavailability 很好，而且 athlete 往往也需要更多 glycine；任何 bioavailable form 应该都可以。

Um the evidence is is is a little bit better for like um there are now several studies in like America in like collegiate American football players where they take a couple of grams of omega-3s every day and across a season you see um less accumulation of uh biomarkers of of injury like neuropilament light that are circulating in the blood. 然后是 omega-3 fatty acid。这方面的证据稍好一些。现在有几项美国 collegiate football player 研究：运动员每天服用几克 omega-3，经过一个赛季后，血液中 neurofilament light 等 injury biomarker 的累积较少。

So that's something that I would just take long like longitudinally. you're somebody who's at risk of a concussion uh because of your sport or your job, I would just, you know, take a reasonable omega-3 supplement just long term because we have some reasonable evidence for that. Then uh other things might become a little bit specific to uh the symptoms that you're experiencing. 所以我会建议长期服用。如果因为 sport 或工作而有 concussion 风险，我会长期服用剂量合理的 omega-3 supplement，因为已经有一些相对不错的证据。其他做法可能需要根据具体 symptom 决定。

So if you have sleep issues, then uh there's studies that have used melatonin and that's shown improvements branch chain amino acids at high doses uh for sleep. And that's interesting because outside of TBI, high doses of branch chain amino acids may actually impair sleep because they compete for tryptophan uptake into the brain, decreasing potentially decreasing serotonin, melatonin uh production. 如果有 sleep issue，有研究使用 melatonin，也显示改善；还有高剂量 branched-chain amino acid 用于睡眠。这很有意思，因为在 TBI 之外，高剂量 BCAA 反而可能损害睡眠：它们会竞争进入大脑的 tryptophan uptake，从而可能减少 serotonin 和 melatonin 的生成。

But in TBI, there are two studies that suggest improvements in sleep with high doses of branch chain amino acids. 但在 TBI 中，有两项研究提示，高剂量 BCAA 能改善睡眠。

嘉宾 If somebody's going to take branch chain amino acids, presumably they're going to look at how much leucine is there for a variety of reasons. Um, so do you recall how much leucine to get this effect post TBI? 如果有人要服用 BCAA，出于多种原因，他大概会。关注其中 leucine 的含量。你记得 TBI 后要达到这个效果需要多少 leucine 吗？

主持人 So I I don't think they at least I don't remember the leucine dose, but they were taking up to 60 g of branches. 我不记得具体 leucine 剂量，至少现在想不起来；但 BCAA 总量最高用到 60 克。

嘉宾 6. Okay. Cuz a typical kind of suggested supplement bottle gym dose would be 3 to five grams. That's usually about six capsules. Yeah. 60 克，好。因为 supplement 瓶上通常建议的健身剂量是 3 到 5 克，大概六粒胶囊。

主持人 So Okay. So like one study they did in uh veterans they had um I think it was three doses of 20 grams AC spread across the day. 对。有一项 veteran 研究好像是每天三次、每次 20 克，分散服用。

嘉宾 Are you curious about um these uh Ibeane studies that are looking at uh you know TBI and brain recovery? I mean Ibeane is a it's a a whole other thing because it's a the the most powerful long-lasting psychedelic at least that I'm aware of. But it seems like there's some interesting data coming out. 你对那些考察 ibogaine 用于 TBI 和 brain recovery 的研究感兴趣吗？ Ibogaine 是另一回事；至少据我所知，它是作用最强、持续时间最长的 psychedelic。不过似乎正出现一些有意思的数据。

Absolutely. Um and then you know in people with a history of brain trauma and PTSD and I think some of these other psychedelics are going to be um very interesting um there as well potentially due to their neuroplastic um effects that tend to particularly happen in like macro doses right in in um in the psychedelic doses. 当然。对于有 brain trauma 和 PTSD 病史的人，ibogaine 以及其他 psychedelic 可能都很值得研究。这也许与它们的 neuroplastic effect 有关，而这种作用通常尤其出现在 macro dose，也就是 psychedelic dose 下。

I think that there's a lot more to come there,but certainly the trials that have been done so far are quite compelling, but that's obviously in in a very controlled kind of clinical setting, heart rate monitor. Again, it's not legal in the United States, although things are shifting. But choline is another thing, particularly acetyloline. 我认为未来还会有很多研究，目前完成的 trial 确实很引人注意，但显然都是在非常严格的 clinical setting 中进行，并监测 heart rate。再强调一次，ibogaine 在美国并不合法，尽管情况正在变化。另一个是 choline，尤其是 acetylcholine。

So um uh best evidence is for 1 to two grams a day um of choline of choline, you know, in the form of CDP choline or citicoline, which is the same thing. Um those are the main ones. Then there's some other like Nisha supplements that do have some evidence. The one that's probably has the most evidence for it is Boswellia. 最好的证据支持每天 1 到 2 克。 Choline？对，以 CDP-choline 或 citicoline 的形式，两者是同一种东西。这些是主要几种。另有一些较小众、也有证据的 supplement，其中证据可能最多的是 Boswellia。

主持人 Boswellia. Boswellia。

嘉宾 Yeah. Uh which is a frank Indian frankincense. But there's an extract of Boswellia that's been tested in I think three different clinical trials after TBI showed some benefit. Enzogenol which I think is a pine extract. Slightly less evidence than Boswellia. I typically would recommend people stick to the first group of kind of nutritional type supplements. um but in very specific um use cases based on specific symptoms some of those other things might be beneficial. 对，也就是 Indian frankincense。某种 Boswellia extract 在 TBI 后做过大约三项 clinical trial，显示了一些益处。 Enzogenol 好像是一种 pine extract，证据比 Boswellia 略少。我通常会建议先考虑前面那组更偏营养类的 supplement，但在非常具体的使用情境中，根据具体 symptom，后面这些也可能有益。

Then beyond that we know that phys return to physical activity as soon as possible is really important after 除此以外，我们知道受伤后尽早恢复 physical activity 非常重要。

主持人 without getting another head injury 但要避免再次撞到头。

嘉宾 without getting another head injury. And you know so so this really changed over the last few years. You know maybe 5 10 years ago people like you know rest is what you need to do. Go lie in a dark room. If you got a concussion in sports, you you would expect the team to have a rigorous return to play protocol that included lowle aerobic activity as soon as you're able to tolerate it u two or three times a week at a level just below what might make your symptoms worse. 对，避免再次 head injury。过去几年里建议发生了很大变化。五到十年前，人们会说 concussion 后需要休息，去黑暗房间躺着。现在如果运动中发生 concussion，team 应当有一套严格的 return-to-play protocol：一旦能够耐受，就开始低强度 aerobic activity，每周两三次，强度保持在不会加重 symptom 的阈值以下。

And then first you do sort of like non-specific aerobic exercise and then you start to bring back skill specific exercises, sports exercises, then go back into full training and then um go back into into playing kind of in that order and that should be quite systematized now. So I would expect sports teams to kind of have have that in place. 先做非专项有氧，再逐步恢复 specific skill exercise、sport-specific exercise，随后回到完整训练，最后恢复比赛，大致按这个顺序。如今这套流程应当已经相当 systematized，所以我预计sports team 都应建立这套机制。一般 standard of care 是 physical therapy。

So like the standard of care is generally phys physical therapy. if you have any ongoing cognitive or physical symptoms sort of a month plus after uh any kind of traumatic brain injury. Um there's some evidence that like virtual reality or augmented reality uh physical uh activity uh might improve cognitive symptoms uh vestibular therapy for balance and dizziness issues. 如果在任何 traumatic brain injury 后一个月以上仍有认知或身体 symptom，一些证据提示 virtual reality 或 augmented reality 中的 physical activity 可能改善认知症状；另外可针对 balance 和 dizziness 进行 vestibular therapy。

And then increasingly uh you know there's um a focus on sort of ocular motor training for like convergence or other eye like um eye issues that are very common after concussions but aren't picked up as often as as people might like. 现在也越来越重视 ocular motor training，用来改善 convergence 或其他 eye issue。

But increasingly kind of eye tracking and these kinds of things are done particularly in professional sports or other arenas after brain injuries to kind of ideally you'd have a baseline you figure out what's changed and then you would track that over time and you can you can train that depending on the deficit. 这些问题在 concussion 后很常见，但过去往往没有得到充分识别。如今在 professional sport 等场景中，brain injury 后越来越常使用 eye tracking 等评估。理想情况下，先有 baseline，再找出受伤后的变化，持续追踪，并根据具体 deficit 进行训练。

主持人 Those recommendations are going to be extremely helpful for people athletes at all levels. I mean, I think for people that don't have access to the, you know, all the latest and greatest, uh, you know, technology and coaches and, uh, nurses and doctors that, um, you know, there's a lot of head hits out there that aren't nec, 这些建议会对各个水平的 athlete 非常有帮助。很多人无法获得最先进的 technology、coach、nurse 和 doctor。生活中有很多 head hit，虽然所幸并没有发展成完整的 brain bleed 或 brain damage，

嘉宾 you know, fortunately aren't um full-blown brain bleeds and brain damage, but the the low-level trauma to the brain is obviously a consideration, especially kids like just falling off the monkey bars. Like parents want to know what they can do. So, thank you very much for those recommendations. You're doing a strongman competition. Uh-huh. All natural. This is not the enhanced games. No. Um, just tell us what the format of that is. Well, first of all, how old are you? 41. 但低程度 brain trauma 显然也值得重视，尤其是孩子从 monkey bars 上摔下来时，家长会想知道能做什么。非常感谢这些建议。你要参加 strongman competition。对。完全 natural，不是 Enhanced Games。不是。给我们介绍一下比赛形式。先问，你多大？ 41 岁。

主持人 Cool. Have you done one of these before? 很好。以前参加过吗？

嘉宾 Yeah, six or seven competitions at this point. I started during CO. I've done like a competition or two every year since then. 到目前为止参加过六七场。我从 COVID 期间开始，此后大概每年参加一两场。

主持人 Mhm. You're a tall guy. You're like 6'2. You weigh 你很高，大约 6 英尺 2 英寸。体重呢？

嘉宾 like 210 215 usually. 通常 210 到 215 磅。

主持人 And is it So, it's height and weight class or just weight class? So, it's weight class. Um, I now so now that I'm older than 40, I compete uh in the mast's category. So, there's a 比赛按身高和体重分组，还是只按体重？

嘉宾 this one of my favorite things about strongman is that if you weigh less than 200 lb, you're a lightweight. So, I'm uh I'm in the lightweight masters category. It means that I usually have to like do a a water cut to like for a weighin cuz I don't normally I'm not I'm normally above 200 lb. Um but yeah, they so they have they have weight they have weight classes and age classes. Can you eat your way and hydrate your way back up to after? 按体重。我现在超过 40 岁，所以参加 masters category。我最喜欢 strongman 的一点是：体重低于 200 磅就算 lightweight。所以我在lightweight masters category。由于我平时超过 200 磅，称重前通常得通过脱水来减重。不过比赛确实同时设置 weight class 和 age class。

嘉宾 Yeah. Like the usually you weigh in 20 hours 24 hours before. I'm I'm definitely back to my usual weight by by the next day. 称重后能靠进食和补水恢复体重吗？可以。通常提前 20 到 24 小时称重，到第二天时我肯定已经恢复到正常体重。

主持人 Gotcha. Yeah. We don't want you trying to lift heavy things dehydrated. What are the big events? So, you're carrying stuff overhead. You're carrying stuff at your sides. You're What are you doing? 明白。我们不希望你在脱水状态下举重。主要 event 有哪些？你会把东西举过头顶，也会在身体两侧搬东西。具体做什么？

嘉宾 A standard kind of local regional competition is five is five events. Um I qualified for the natural like world's strongest man uh which is going to be seven events. But there's usually um some kind of deadlift, some kind of overhead pressing event, uh some kind of um medley where you're like carrying something, lifting stones, farmers walks. So in um truck pull, something like that. So like more dynamic. 标准的本地或区域比赛通常有五个 event。我取得了 natural World's Strongest Man 的参赛资格，那里会有七项。通常包括某种 deadlift、某种 overhead press，以及某种 medley，需要搬运物体、举 stone、做 farmer's walk，也可能有 truck pull 之类，更具动态性。

So there's like usually like a static max strength thing, but then also like more dynamic. 通常既有静态最大力量项目，也有更动态的项目。

主持人 The teeth you do the teeth pull the 会用牙齿拉吗？

嘉宾 Oh, no. No teeth. Uh no, no teeth pulling. Um the we didn't talk about oral health and cognitive function, but that's really important too. The events in the competition that I've got coming up, the the world's strongest, there's going to be a farmer's walk. So that's where you just like pick things up at the side and kind of 不，不用牙齿。我们没谈 oral health 与认知功能，不过它也很重要。接下来 World's Strongest Man 的项目中有 farmer's walk，就是从身体两侧把重物提起来走。

主持人 So for a guy, let's say you you hydrate back to like 2 205 210 or something like that. What what what's a good distance and weight to carry? 假设你补水后恢复到 205 或 210 磅左右，搬多重、走多远算不错？

嘉宾 I know the weight in the competition. It's 120 kilos per hand. So that's 264 pounds per hand. Um and as far as you can as far as you can carry it. Um I can't remember if 我知道比赛重量：每只手 120 公斤，也就是每只手 264 磅，要尽可能走远。我不记得——

主持人 that's a big human in in each hand. 这等于每只手提着一个大块头的人。

嘉宾 Yeah. Um so typically, you know, if you if you can get to where you've got like your body weight in each hand and you're able to pick it up and move with it, even if it's not very far, I think that's pretty good. Um but like, you know, some people might say half your body weight. In reality,if you pick something up heavy and move with it, that's great. Like, and then get better. We're not talking about recommendations. This is your time to shine, my friend. 对。一般来说，如果每只手都能提起约等于自己体重的重量并带着它移动，哪怕走不远，我认为也很不错。不过也有人会说，每只手提一半体重就很好。现实中，只要能提起重物并带着它移动，就很棒，然后再逐步进步。我们现在不是给普通人建议，这是你展示实力的时候，朋友。大家可以慢慢练上来。我看 Tom Haviland 的 Instagram，我们会放链接，大家都应该看看。

People can work their way up. I I I watch uh Tom Havlin's um uh Instagram. We'll put a link to it. Everyone should see that. His wife and his kid also work into the workouts. He's got a But man, he's strong. But yeah, carrying heavy weight. No, no, this is not your time to tell people how to tiptoe into it. That's a different podcast. So, you're carrying 220 lbs in each hand. 264 lbs per hand and walking how far? 他妻子和孩子也会加入训练。天啊，他真的很强。总之，就是搬运很重的重量。别在这里告诉大家怎么循序渐进，那是另一期节目。所以你每只手提 220 磅？每只手 264 磅。要走多远？在规定时间内尽可能走远，我不记得是 60 还是 90 秒。

It's maximum distance um in I can't remember if it's 60 or 90 seconds. You can set it down. You can set it. You can set it down. So, it's as far as you can get in that period of time. And it'll be similar with a with a yoke walk. So, there's a a yoke where you know sort of like put it on your back. It's 700 lb. How far can you how far can you walk in that period of time? Love this. So primitive. Love it. Pure hypothalamic event. 中途可以放下吗？可以放下。所以就是在限定时间内尽可能走远。 yoke walk 也类似：把 yoke 扛在背上，总重 700 磅，看你在规定时间内能走多远。太喜欢了，太原始了，纯粹是 hypothalamic event。对。 yoke walk 的终点好像是 30 米，大约 90 英尺。

Yeah. So, in that event in the in the yoke walk, if you get to the end, I think it's 30 I think it's 30 m 90ish feet. If you can carry that in that far in the time cap, then you do reps on a circus dumbbell. So like this this big massive dumbbell that you have to like shoulder to overhead. There's one at 110 lb and the next is at 135 lb. Then there's going to be a loading medley. So sandbags and kegs uh like over over a platform that's like I think 200 to 300 lb implements. 如果能在时间上限内把它搬到终点，接着就做 circus dumbbell rep，也就是把一个巨大的 dumbbell 从肩上举过头顶。先用 110 磅，下一只 135 磅。然后还有 loading medley。要把 sandbag 和 keg 举过一个平台，器械重量大概是 200 到 300 磅，并逐渐增加。

They kind of increase over time. Um there's a maximum squat and you have a choice of two different um weights. Um, and so like if you choose the bigger weight and you get reps on the bigger weight that you get a better score than somebody standard back squat. It's a standard back squat is with an axle bar. So like a thick bar. Um, and then in strongman when you have squatting you usually have pads that you squat down to. So there's a specific height you squat down to. 还有 max squat，可以从两个不同重量中选择。如果选择更大的重量并完成 rep，得分会高于选择较轻重量的人。标准 back squat？是标准 back squat，但使用 axle bar，也就是更粗的杠铃。 Strongman 做squat 时，通常会在身后放 pad，要求下蹲到特定高度、让重量触到 pad。

主持人 Um, so like that could give you an advantage if you're shorter, right? Because you have to go less distance to get the weight on the pads. But like 那身材较矮可能有优势，因为重量移动到 pad 的距离更短。可不能耍花招，把不到完整一次的动作也算一 rep。

嘉宾 but there's no geeking it and calling less than a one rep. Yeah, people have done that. It doesn't look good. 有人这么做过，看起来很不好。

主持人 Yeah. No, no. Like it just has to hit the pads and come back up. And the weights are 170 kilos and 200 kilos. So that's 对，重量只要触到 pad 再站起来就算。两个重量是 170 公斤和 200 公斤，也就是

嘉宾 what uh nearly 400 lb and 440 lb uh log press um for reps. And again, it's a similar style. And I I think it's 100 kilos. So 220 lb and then 120. So 264. And then there's a sled like you uh I think you push a sled and then you load it with a 275 lb sandbag and then you drag it um in a in a time cap. I think that I think that's all the events. 接近 400 磅和 440 磅。还有按次数计算的 log press，形式类似。我想两个重量是 100 公斤，也就是 220 磅，以及 120 公斤，也就是 264 磅。然后还有 sled：先推 sled，再往上装一个 275 磅的 sandbag，之后在限定时间内把它拖回来。我想项目应该就这些。

主持人 Awesome. Uh you'll let us know when it is. 太棒了，到时告诉我们比赛日期。

嘉宾 Yes. Uh it's at the end of August. 八月底。

主持人 Cool. Will it be online? 很好，网上能看吗？

嘉宾 Uh it won't be online, but I'm sure there'll be some stuff on Instagram. 不会在线直播，不过 Instagram 上肯定会有一些内容。

主持人 Cool. I I love that you do this. Uh clearly um you got a lot of brains in that. uh skull of yours and you you're also super strong. Love hearing it. That's that's great. And and uh you have no excuse not to carry the groceries at home, right? So you you lost that that ride. But there's no doubt you would. Anyway, that's awesome. 很好，我很喜欢你参加这项比赛。你脑袋里显然装了很多知识，身体又超级强壮，听起来太棒了。所以你在家没借口不拎 groceries，对吧？这项特权已经没有了，不过毫无疑问你本来就会去拎。

I I I'm very impressed by the by people who continue to take on athletic challenges in their uh in their adult life as which is very appropriate to context today. So Dr. Tommy Wood, thanks for coming out today. I learned a ton from you and you know going into this I like I like to think I know a thing or two about plasticity having spent so much time in it and studying it over the years but I learned a lot from you today and I know everyone else did as well. 总之，真的很棒。成年人仍不断接受 athletic challenge，我对此非常佩服，也与今天的主题很契合。 Tommy Wood 博士，感谢你今天来做客。我从你这里学到了很多。节目开始前，我自认为研究 plasticity 多年，对它还算了解，但今天仍学到了很多，我知道其他人也是如此。

You're an exceptionally clear communicator and um you're working on not just an important issue you're working on the issue uh this neuroplasticity thing and a whole lot more. 你的表达异常清晰，而且你研究的不只是一个重要问题，而是那个核心问题——neuroplasticity，当然还有更多内容。

So, let's definitely get you back to talk about recovery from brain injury and stroke and things of that sort because there's a lot of uh additional things I think we could dig into,but uh meanwhile, you've given us a lot of uh actionable tools and um yeah, I I love that uh you're doing the strongman competition and uh come back again. We appreciate you. 我们一定要再请你回来，讨论 brain injury、stroke 后的恢复等，因为还有很多内容值得深入。不过今天你已经给了我们大量可以采取行动的工具。我也很喜欢你参加 strongman competition。欢迎再来，非常感谢你。

嘉宾 I will. Thank you so much. 我会的，非常感谢。

主持人 Thank you. Thank you for joining me for today's discussion with Dr. Tommy Wood. To learn more about his work and his book, please see the links in the show notes caption. If you're learning from and or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific zerocost way to support us. In addition, please follow the podcast by clicking the follow button on both Spotify and Apple. And on both Spotify and Apple, you can leave us up to a fivestar review. 谢谢。感谢大家收听今天与 Tommy Wood 博士的讨论。想进一步了解他的工作和书籍，请查看 show notes 中的链接。如果你从本播客中有所收获或喜欢节目，请订阅我们的 YouTube channel，这是支持我们的绝佳免费方式。也请在 Spotify 和 Apple 点击 follow；在这两个平台上，你都可以留下最高五星评价，现在也都可以发表评论。

And you can now leave us comments at both Spotify and Apple. Please also check out the sponsors mentioned at the beginning and throughout today's episode. That's the best way to support this podcast. If you have questions for me or comments about the podcast or guests or topics that you'd like me to consider for the Hubberman Lab podcast, please put those in the comment section on YouTube. I do read all the comments. 也请关注本期节目开头及过程中提到的 sponsor，这是支持本播客最好的方式。如果你有问题、对节目或嘉宾的意见，或者希望 Huberman Lab Podcast 考虑某个主题，请在 YouTube comment section 留言，我会阅读所有评论。还没有听说的朋友，我有一本新书即将出版，也是我的第一本书，名为《Protocols: An Operating Manual for the Human Body》。

For those of you that haven't heard, I have a new book coming out. It's my very first book. It's entitled Protocols, an operating manual for the human body. This is a book that I've been working on for more than 5 years, and that's based on more than 30 years of research and experience. And it covers protocols for everything from sleep to exercise to stress control protocols related to focus and motivation. 我为这本书投入了五年多时间，内容建立在三十多年的研究与经验之上，涵盖从睡眠、运动、压力调节，到专注和动机等各类 protocol；我当然也会提供书中 protocol 的科学依据。现在可以在 protocolsbook.com 预购，网站上有不同vendor 的链接，可以选择你喜欢的一家。

And of course, I provide the scientific substantiation for the protocols that are included. The book is now available by pre-sale at protocolsbook.com. There you can find links to various vendors. You can pick the one that you like best. Again, the book is called Protocols, an operating manual for the human body. And if you're not already following me on social media, I am Huberman Lab on all social media platforms. So that's Instagram, X, Threads, Facebook, and LinkedIn. 再说一次，书名是《Protocols: An Operating Manual for the Human Body》。如果你还没有在 social media 关注我，我在所有平台上的账号都是 Huberman Lab，包括 Instagram、X、Threads、Facebook 和 LinkedIn。

And on all those platforms, I discuss science and science related tools, some of which overlaps with the content of the Huberman Lab podcast, but much of which is distinct from the information on the Hubberman Lab podcast. Again, it's Huberman Lab on all social media platforms. 我在这些平台讨论 science 和相关工具，其中一些与 Huberman Lab Podcast 重叠，但很多内容是节目中没有的。再次提醒，所有 social media平台上的账号都是 Huberman Lab。

And if you haven't already subscribed to our neural network newsletter, the neural network newsletter is a zerocost monthly newsletter that includes podcast summaries as well as what we call protocols in the form of 1 to three-page PDFs that cover everything from how to optimize your sleep, how to optimize dopamine, deliberate cold exposure. We have a foundational fitness protocol that covers cardiovascular training and resistance training. 如果还没有订阅 Neural Network Newsletter，这是一份完全免费的月刊，包含 podcast summary，也包含我们称为 protocol 的 1 到 3 页 PDF，主题涵盖优化睡眠、优化 dopamine、deliberate cold exposure；我们还有一套 foundational fitness protocol，覆盖 cardiovascular training 和 resistance training。

All of that is available completely zero cost. You simply go to hubmanlab.com, go to the menu tab in the top right corner, scroll down to newsletter, and enter your email. And I should emphasize that we do not share your email with anybody. Thank you once again for joining me for today's discussion with Dr. Tommy Wood. And last, but certainly not least, thank you for your interest in science. 所有内容完全免费，只需前往 hubermanlab.com，打开右上角 menu，向下滚动到 newsletter，输入 email。需要强调的是，我们不会与任何人分享你的 email。再次感谢大家收听今天与 Tommy Wood 博士的讨论。最后同样重要的是，感谢你对 science 的兴趣。