#363 ‒ 神经外科新前沿：通过脑机接口恢复大脑功能、推进胶质母细胞瘤治疗，以及为毁灭性脑疾病带来新希望 | Edward Chang 医学博士

大家好，欢迎收听《驾驶》播客。我是主持人彼得·阿提亚。本播客、我的网站以及每周通讯都致力于将长寿科学转化为人人可及的内容。我们的目标是提供最优质的健康与保健内容，并已组建优秀的分析师团队来实现这一愿景。

Hey, everyone. Welcome to the Drive podcast. I'm your host, Peter Attia. This podcast, my website, and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content in health and wellness, and we've established a great team of analysts to make this happen.

对我而言，在不依赖付费广告的情况下提供所有这些内容至关重要。为此，我们的工作完全由会员支持得以实现。作为回报，我们提供专属会员内容和福利，远超免费可获取的内容。若您想在此领域深化认知，我们的目标是确保会员获得的回报远超订阅价格。如需了解更多高级会员福利，请访问 peteratiamd.com/subscribe。

It is extremely important to me to provide all of this content without relying on paid ads. To do this, our work is made entirely possible by our members. And in return, we offer exclusive member only content and benefits above and beyond what is available for free. If you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of the subscription. If you want to learn more about the benefits of our premium membership, head over to peteratiamd.com slash subscribe.

本周我的嘉宾是爱德华·张医生。爱德华是加州大学旧金山分校神经外科主任，也是功能神经外科和脑机接口领域的领先创新者。他的工作连接手术室、研究实验室和工程台，旨在为失去言语和行动能力的患者恢复这些功能。在本期节目中，我们探讨现代神经外科如何演变，大幅减少附带损伤和恢复时间。

My guest this week is Doctor. Edward Chang. Edward is the chair of neurosurgery at UCSF and a leading innovator in functional neurosurgery and brain computer interface. Edward's work bridges the operating room, the research lab and the engineering bench to restore speech and movement for patients who have lost these traits. In this episode, we discuss how modern neurosurgery evolved, dramatically reducing collateral damage and recovery time.

清醒脑部手术期间会发生什么，为何大脑感觉不到疼痛，实时映射如何保护语言和运动功能，以及外科医生在功能皮层边缘做出的瞬间决策。脑机接口的突破性进展。神经工程的下一个前沿：完全可植入无线脑机接口和功能性电刺激系统，可能绕过受损神经以恢复呼吸或肢体控制。基因组分析、免疫策略及更广泛切除如何逐步将一度普遍致命的胶质母细胞瘤转变为生存期稍长的疾病。爱德华对2030年及未来的愿景：更纤薄、更安全的脑植入物为瘫痪和其他损伤患者恢复言语，以及这些进展如何帮助将肌萎缩侧索硬化症、脊髓损伤甚至侵袭性脑瘤转变为更慢性可控的疾病。事不宜迟，请欣赏我与医生的对话。

What happens during awake brain surgery, why the brain feels no pain, how real time mapping protects language and motor function, and the split second decisions surgeons make at the edge of the eloquent cortex. Breakthroughs in brain computer interfaces. Neural engineering's next frontier fully implantable wireless brain computer interfaces and functional electrical stimulation systems that may bypass damaged nerves to restore breathing or limb control, How genomic profiling, immune based strategies and more extensive resections are slowly turning glioblastoma, a once uniformly fatal tumor, into a slightly longer survivable disease. Edward's vision for 2030 and beyond, slimmer, safer brain implants to restore speech for people with paralysis and other injuries, and how advances will help turn conditions like ALS, spinal cord injury and even aggressive brain tumors into more chronic manageable illnesses. So without further delay, please enjoy my conversation with Doctor.

爱德华·张。贝蒂，非常感谢你在百忙之中抽出时间来到奥斯汀。今天能与你交谈，我感到非常兴奋。哦，我很高兴来到这里。谢谢你，彼得。

Edward Chang. Betty, thank you so much for taking time out of your very busy schedule to come to Austin. Really excited to talk with you today. Oh, I'm thrilled to be here. Thanks Peter.

关于你今天的职业领域、神经外科的现状以及其边界如何被不断拓展，我有很多话题想探讨。但正如我们之前谈到的，我认为神经外科仍有些神秘，或许通过一点历史回顾能帮助听众更好地理解。让我们回到19世纪末期，那时神经外科医生通常会遇到哪些典型问题？他们手头有哪些工具可用？假设我们讨论的是麻醉技术发展之后的时期，这样就不至于完全陷入需要按住病人的恐怖场景。这真是个非常有趣的问题。

So there's so much I want to talk about with respect to what your career is about today and what the field of neurosurgery is in today and how the bounds are really being pushed. But as we were talking earlier, I think that neurosurgery remains a little bit of a black box and it might help orient our listeners if we give a little bit of a history lesson. So can we orient ourselves back into the latter part of the nineteenth century and what were the typical problems that would have presented to a neurosurgeon and what were the tools that they had at their disposal? And let's posit that we're speaking after the development of anesthesia at least, so we're not in completely gruesome lands of holding people down. That is a really interesting question.

神经外科之所以显得有些神秘，部分原因在于人们常将其视为极限医学——一小群医生负责治疗病情严重的患者，这是个需要极长培训周期的精专领域。但若回溯一百年，我们谈论的是哈维·库欣的时代，他被誉为现代神经外科之父。我认为那确实是医学史、神经科学史和神经外科史上的一个明显转折点，堪称现代神经外科的真正开端。

And one of the reasons neurosurgery is a little bit of a black box is in many ways, people consider it sort of like extreme medicine. It's like a very small group of physicians that are taking care of patients with fairly severe indications, a really rarefied field that takes very long training in addition. But let's say we go back one hundred years. We're talking about the era of Harvey Cushing, who's considered really the father of modern neurosurgery. I think that was a clear inflection point in the history of medicine, in the history of neuroscience, in the history of neurosurgery, really the beginning of what we would call modern neurosurgery.

我认为库欣之所以如此强大，除了他进行非凡手术的能力外，还在于他的观察力。因此，除了是一位非常敏锐的观察者，除了是一位技术极其精湛的外科医生，我认为他也是一位了不起的内科医生，诊断出了一些最早的垂体瘤及其对内分泌功能的影响。然后，真正开启了现代开颅手术的时代，即打开颅骨以接触脑肿瘤。自那以后，一切都随之发展起来。神经外科的主要类别涉及肿瘤、血管系统（包括动脉瘤、中风和血栓）、脊柱，以及可能最近的一个是我们称之为功能神经外科的领域，它实际上涉及理解大脑回路的功能，同时也通过深部脑刺激或其他消融方法来干预以改变其工作方式。

Why I think that Cushing was so powerful was his observation, in addition to his ability to do extraordinary surgeries. So in addition to being really an astute observer, in addition to being an incredibly technically skilled surgeon, I think he was also an incredible internist, too, diagnosing some of the first pituitary tumors and the effects of those on endocrine function. And then, really, the era of modern tools of craniotomy, opening the skull to get access to brain tumors. And everything followed since then. The main categories of neurosurgery have to do with tumors, the vascular system, which are aneurysms and strokes and blood clot, spine, and then probably the most recent one is the one we call functional, which actually has to do with understanding the functions of brain circuit, but also intervening to change how they work using deep brain stimulation or other ablation methods.

这些是真正令人兴奋的新进展。而且我认为哈维·库欣也会因电灼术的发展而受到赞誉，不是吗？绝对是。很难想象没有这些东西怎么能做手术。是的，不仅仅是在大脑中，而是在身体的任何地方。

Those are the really exciting new developments. And I think Harvey Cushing would be credited for the development of the electrocautery as well, wouldn't he? Absolutely. It's hard to imagine that you could operate without one of those things. Yeah, and not just in the brain, but anywhere in Anywhere in body.

是的，这是在任何手术中控制出血的关键。但特别是在大脑中，这是一件棘手的事情。所以哈维·库欣只是现代神经外科的起点。然后是怀尔德·潘菲尔德，他是美国人，但在创建蒙特利尔神经学研究所方面做了一些令人难以置信的工作。那确实是我们所认为的现代癫痫外科手术的开端。

Yeah, it's the key of controlling bleeding in any surgery. But particularly in the brain, it's a tricky thing. And so Harvey Cushing was just the starting point of modern neurosurgery. Then there's Wilder Penfield, who was an American but really did some incredible work in creating the Montreal Neurological Institute. And that was really the beginning of what we'd consider modern epilepsy surgery.

所以这些手术旨在阻止人们癫痫发作。他推广了这个我们都在医学院学习的东西，叫做“小人图”。就是那张图片，对吧，那个小人在我们大脑中 essentially 控制身体每一块肌肉的部分，以及它如何在大脑的那个特定部分布局，这是我们都要学习的东西。他也是一位杰出的科学家，帮助我们理解了一些关于语言的基本知识，并且从技术角度，真正推广和发展了清醒脑部手术的概念。这真的是自从医学院以来就吸引我的东西，也是我现在专攻的领域。

So surgeries that are designed to stop people from having seizures. And he popularized this thing that we all learn in medical school called the homunculus. It's this picture, right, of the little man there in essentially the part of our brain that controls every muscle in our body and how it's laid out in that particular part of the brain, it's something that we all learn. He was also a brilliant scientist who helped us understand some of the basic things that we know about language, and from a technical perspective, really popularized and developed the concept of awake brain surgery. And that's really something that's captivated me since medical school and what I now specialize in now.

所以让我们快进一点，到你我上医学院之前的时代，比如70年代和80年代。大约四十、五十年前，在血管管理、脑部肿块的肿瘤管理方面，与今天相比，技术水平如何？所以撇开介入方面的事情，仅就能否对大脑进行手术而言，技术的平台期在哪里？有趣的是，我们现在做的一些事情几乎与库欣100多年前的做法完全相同。而有些则截然不同。

So let's fast forward a little bit into an era before you and I were in medical school, call it the 70s and the 80s. What was the state of the art, call it forty, fifty years ago with respect to the vascular management, the oncologic management of masses in the brain relative to today? So exclusive of the interventional side of things, just in terms of being able to operate on the brain, where were the plateaus in technology? What's interesting about it is some of the things that we do now are almost identical to the way that Cushing did it over 100 ago. And then some of it is radically different.

所以我们做的一种主力手术叫做开颅手术。这基本上意味着你暂时移除一块骨头，在手术结束时再放回去，以接触到像位于额叶或颞叶的脑肿瘤这样的东西。这种方法今天仍在进行，并且仍然非常适用。但我们现在所处的位置是，有方法可以通过非常小的切口使用激光探针到达大脑深处的目标进行消融。现在甚至有方法使用聚焦超声，可以靶向大脑深部的特定核团，以控制某人的震颤，例如。

So one of the workhorse surgeries that we do is called a craniotomy. And that basically means where you remove a piece of bone temporarily, you place it at the end of the procedure to access something like a brain tumor that's in the frontal or temporal lobe. That's still being performed today and still really indicated. But where we are now, there's ways of using laser probes through very small incisions to get to deep targets in the brain to ablate them. There are ways of now even using focused ultrasound that can be targeted to specific nuclei in deep parts of the brain in order to control someone's tremor, for example.

这被我们视为一种相对非侵入性的神经外科方法。所以事情已经发生了根本性的变化。我想说，我们看到巨大颠覆的另一个领域实际上是血管神经外科领域。所以在80年代和90年代，你会做一个大的开颅手术和切口，可能大约七到九英寸长，移除一块骨头，然后使用手术显微镜解剖到血管所在的深处进行修复，比如说，修复一个动脉瘤，这 essentially 是血管的 ballooning，当它破裂时可能是致命的。所以这是我受训时做的很多工作。

This is what we consider a relatively non invasive approach to do a neurosurgery. So things have changed radically. I would say one other area where we have seen tremendous disruption actually is in the vascular neurosurgery field. So back in the '80s and '90s, you'd have a large craniotomy and incision, probably about seven to nine inches long, removal of a piece of bone, and then using an operative microscope to dissect down to the deepest parts where the blood vessels are coming to fix, let's say, an aneurysm, which is essentially a ballooning of a blood vessel that, when it ruptures, can be fatal. And so that is a lot of what I trained on.

如今，90%的这些手术都是通过腹股沟导管在可视化下完成的。我们将线圈放入动脉瘤中以加固它们。我们现在还可以放置支架。这实际上是一个巨大的变化。现在我们已经能够取出并溶解导致急性严重中风的血栓。

Nowadays, ninety percent of those procedures are now done through a catheter in the groin that's visualized. We put coils into the aneurysms to help secure them. We can now do stents. Huge change actually now. It's been able to now being able to retrieve and dissolve clots that are causing acute, severe strokes.

这些可能是我们见过的最戏剧性的情况，有人进来时不能说话，身体一侧瘫痪。在过去，我们只能给一些药物，祈祷它能起作用。但很少奏效。真正受益的病例确实是少数。但如今，有很大比例的患者可以通过植入设备来取出中风血栓。

Those are probably the most dramatic things that we've seen, someone come in not able to talk, paralyzed on half side of the body. In the old days, we would just give some medications, keeping our fingers crossed that that would work. It rarely worked. It was really the minority of cases that it helped. But nowadays, there's a much bigger fraction of patients where you can put the device in, retrieve the stroke.

当有人在经历如此重大的事件后第二天就能回家时，这些确实是改变游戏规则的事情。所以我们开始看到中风变得更像心脏病发作。导管实验室不仅治疗心脏病发作，还治疗我们所谓的脑部发作或中风。所以有些事情在两百年前相对相似，而有些事情则完全改变了。因此，如果三十年前神经外科医生在做开颅手术，几乎每次都是在处理病理，那么今天可能不到一半的时间？

And these are really game changing things when someone can go home the next day after such a huge thing. So we're starting to see things like stroke become more like heart attacks. The cath labs are not just treating heart attacks, but they're also treating what we call brain attacks or strokes. So some things are relatively similar two hundred years ago and then some things have just been totally changed. So if thirty years ago a neurosurgeon was doing a craniotomy, virtually every time they were addressing pathology, today it might be less than half the time?

是的，没错。这与我们在外科其他部分看到的情况并非不相似。几周前我刚和一位血管外科医生聊天，他和我差不多时间完成培训，我问他，你知道，你现在做多少开放式手术？他谈到腹主动脉瘤（AAA）和各种股腘动脉手术之类的。他说，是的，我们现在很少做开放式手术了。

Yeah, that's right. That's not a dissimilar parallel to what we see in other parts of surgery. I was just talking to a vascular surgeon a couple of weeks ago, finished his training around the time I did and I said, you know, how many open surgical procedures are you doing? Know, was talking about triple As and all sorts of, you know, fem pops and things like that. And he said, yeah, we do very little open these days.

几乎都是通过支架完成的。这再次让我震惊，比如颈动脉手术，整个事情，他们现在做的手术如此之少，真是让我大吃一惊。我指的是传统意义上的开放式手术。显然他们仍然在进行干预。是的，绝对是的。

It's virtually all done with stents. Which again, even see like carotid arteries, the whole thing, I was really blown away at how little they are operating now. Meaning operating in an open sense. Obviously they're still intervening. Yeah, absolutely.

我认为外科手术发生的变化不是一种趋势。这是一股进化的力量，引导我们走向更微创、对目标造成更少附带损伤、让人们更快回归生活的方法。有了所有这些新技术的加入，这实际上是一个医学上非常令人兴奋的时代。如果你能适应这种变化，那绝对是一个激动人心的时刻，是的。我知道这不是你感兴趣的领域，所以请随意说，是的，我对它了解不够。

I think what's happened with surgery is that this is not a trend. This is the force of evolution that is guiding us towards things that are more minimally invasive, less collateral damage to get to the targets and getting people back to life sooner. And it's a very exciting time, actually, to be in medicine with all this technology that's coming on board. If you're okay with that change, it's absolutely thrilling time, yeah. Now, I know this is not your field of interest, so feel free to say, Yeah, I don't know enough about it.

但每当我想到大脑，我就会想到胶质母细胞瘤（GBMs）。我会想到这些可怕的肿瘤，我想对于听众我们可以解释一下那是什么。所以，也许告诉人们什么是GBM，为什么GBM确实是让癌症名声扫地的癌症之一。我想我真正想问你的问题是，鉴于传统手术历史上从未对这种肿瘤起过作用，你根本无法解决它，并且考虑到从开颅手术、大型开放式手术的转变，对于GBMs来说，是否有任何前景可以使它们变得不那么致命？是的。

But whenever I think of the brain, think of GBMs. I think of these awful tumors, which I guess for the listener we can explain what that is. So, maybe tell folks what a GBM is, why a GBM is truly one of the cancers that gives cancer a bad name. And I guess my real question for you is, given that traditional surgery has historically never worked for this tumor, you simply can't resolve it, and you think about the transition away from craniotomy, big open procedure, is there anything on the horizon for GBMs to render them less lethal? Yeah.

所以GBM代表胶质母细胞瘤，这个词说起来很拗口。如果拆解来看，它指的是，这个词中的胶质部分指的是细胞起源。大脑有不同类型的细胞，如果从大类来看，有神经元，它们主要负责我们的思维和功能。然后还有一大群支持细胞，我们称之为胶质细胞，这就是第一部分。胶质母细胞瘤起源于这些支持细胞群。

So GBM stands for glioblastoma multiforme, and it's a mouthful of a word. If you break it down, what it's referring to, the glial part of that word refers to the cell origin. The brain has different types of cells and if you look in the big buckets, there's neurons which are the ones that primarily are the ones that allow us to do thinking and function. And then there's a large population of support cells that we call glia and that's that first part. Glioblastoma originates from those support cell population.

多形性指的是这些肿瘤在组织学上的原始描述，确实显示出多种形态、多种组织学特征。它的一些关键特征包括坏死。肿瘤生长得如此之快，以至于超出了其血液供应，并在其过程中留下细胞死亡，我们称之为坏死。所以就像你提到的，这确实是一种可怕的疾病和状况。我们正在取得进展，特别是在理解病因方面。

Multiforme refers to these original descriptions histologically of the tumors that really showed multiple form, multiple histology. Some of the key features of it are the necrosis. The tumor grows so quickly that it outstrips its blood supply and in its wake it leaves cell death, what we call necrosis. So like you alluded to, it really is a terrible disease and condition. We are making progress and specifically around understanding what causes.

就在十年前，你会切除其中一个肿瘤，送到实验室，可以得到诊断这是胶质母细胞瘤。现在，在大多数学术医疗中心，你还会得到肿瘤的基因图谱。所以如今，我们实际上知道肿瘤具体涉及哪些突变，这对于下一章至关重要，即利用这些基因改变来量身定制和个性化化疗等。这具有重大意义，因为我们正从一个使用组织学可视化的时代转向更机制化的分子图谱分析。新的化疗药物将真正针对机制，而不是像细胞周期和代谢等一般性事物。

So just ten years ago, you would remove one of these tumors, you send it to the lab, you could get the diagnosis that this is a glioblastoma. Now, in most academic medical centers, you'll also get a genetic profile of the tumor. So nowadays, we actually know specifically what kind of mutations are involved in the tumor and that's going to be really critical for this next chapter, which is using those genetic alterations actually to tailor and personalize chemotherapy and more. So this has big implications because we're now moving from an era where we use a visualization of the histology now to this molecular profiling, which is more mechanistic. The new chemo agents are really going to be targeting mechanisms as opposed to general things like cell cycle and metabolism and things like that.

所以这些是正在改变的事情，我们需要它改变得更快。还有一些非常令人兴奋的事情，我们看到了训练免疫细胞靶向目标的新方法。事实证明，胶质母细胞瘤实际上会抑制免疫系统的部分功能，它们有点像在 stealth 模式下生长，并以一种 cloak 方式激活分子和细胞，使其无法再被免疫细胞识别。因此，如果我们基本上能让肿瘤被免疫系统识别，这可能是未来真正解锁疗法的东西。但我们确实知道目前效果相当好的事情，至少在延长患者生存期和真正有意义的生存方面，实际上仍然围绕手术。

So these are the things that are changing, and we need it to change faster. There are also really exciting things that we're seeing around new ways to train the immune cells to target things. It turns out that glioblastomas actually suppress parts of the immune system, they're kind of like growing in stealth and they activate molecules and cells in a cloak way that can't be recognized by immune cells anymore. And so if we can basically allow the tumors to be recognized by the immune system, that could be something that really unlocks therapy in the future too. But the things that we do know that work pretty well right now, at least in terms of prolonging survival for patients and really meaningful survival, actually still is around the surgery.

我们确实知道，切除范围越广泛，生存期越长，这一点现在已经得到了很好的表征。但它不是治愈性的，就像你说的。我们可以切除百分之九十九甚至百分之百，甚至超出我们在MRI上看到的范围。不幸的是，通常有显微镜下的细胞超出了我们在MRI上能看到的范围，仍然存在，并随着时间的推移会重新 populate 肿瘤。这是一种非常复杂和棘手的疾病，但我们正在非常努力地研究它。

We do know that the more extensive the resection, the longer the survival is, and that's been really well characterized now. But it's not curative, like you said. We can remove ninety nine percent or even one hundred and beyond what we see on the MRI. Unfortunately, there's usually microscopic cells that go beyond what we can see on the MRI that are still there and over time will repopulate the tumor. It is a really complicated and tough disease, but we're working really hard on it.

从风险角度来看，我们是否知道什么使个体易患此病？简短的回答是否定的。因为它影响年轻人，也影响老年人。我的意思是，我见过儿童、青少年、中年人和临终者死于这种疾病。它似乎没有明显的模式。

Do we have any idea what predisposes an individual to this from a risk perspective? Short answer is no. Because it afflicts young, it afflicts old. I mean, I've watched children die of this, teenagers, people in midlife, people at the end of life. It seems to have no apparent pattern.

是的。部分原因与其机制有关。我们不认为它是一种可遗传的风险。但它依赖的是一组突变，而且很少是同一组突变。对。

Yeah. And part of that has to do with its mechanisms. It's not something that we consider as a heritable risk. But what it does rely on is a set of mutations, and it's rarely the same set. Right.

这是一种高度多基因的疾病。没错。这正是治疗起来非常棘手的原因。当我们谈论胶质母细胞瘤时，我们实际上不是在谈论单一事物，而是在谈论一个基因改变的系统，这些改变共同级联形成了我们所见的形态。

It's a very polygenic condition. Exactly. And that's what makes it really tricky to treat. When we talk about glioblastoma, we're actually not talking about one thing. We're talking about a system of genetic alterations that together have cascaded into the form that we see.

埃迪，我猜我们还会回到这个话题，但你提到了化疗药物，无论是用于治疗胶质母细胞瘤还是其他疾病，包括扩散到大脑的其他上皮癌转移瘤。血脑屏障对治疗构成了挑战。你认为未来的方向在于脑脊液内治疗吗？比如直接鞘内注射或直接进入中枢神经系统治疗？还是设计能够穿越血脑屏障的药物？

And I suspect we'll come back to this, Eddie, but you've alluded to chemotherapeutic agents that can be used, whether it's to treat glioblastoma or anything else, including mets of other epithelial cancers that spread to the brain. The blood brain barrier poses a challenge for treatment. Do you think the future lies in treatment within the CSF? So treating directly inside intrathecally or directly into the central nervous system? Or do you think it's designing drugs that cross the blood brain barrier?

我的意思是，你认为未来会是什么样子？我认为会是以上所有方式的结合。这种情况下我们需要考虑所有可能的选项。这不像我们考虑非侵入性或微创性那样，真正重要的是首先找到有效的方法。我密切关注的一项技术发展——我们正在UCSF进行相关研究——是使用聚焦超声。

I mean, do you think the future looks like? I think it's going look like all of the above. This is a situation where we do need to look at all possible options. This is not like the kind of thing where we're thinking like non invasive or minimally invasive, really something that will work is the first priority. One of the technologies I'm really interested in following how this develops, and we're doing research on this at UCSF, is using focused ultrasound.

大多数人都知道超声用于诊断，但如果改变其能量特性，实际上可以利用超声的声能打开血脑屏障和大脑的特定区域。因此有很多研究致力于将其作为一种递送方式，而不是直接在大脑中放置导管之类的东西。然后配合那些一旦血脑屏障打开后就能分子级精准靶向的新药剂。是什么吸引你从事神经外科？是读医学院时就知道自己想做这个吗？

So most people know about ultrasound to diagnose, but if you change the energy profile of it, you can actually use acoustic energy through an ultrasound to actually open up the blood brain barrier and targeted parts of the brain. And so there is a lot of development on using that as a way to do delivery as opposed to putting a catheter or something directly in the brain. Then with that set of new agents that can be really molecularly specific to get to targets once you open up that blood brain barrier. What attracted you to neurosurgery? Was it something you knew you wanted to do when you went to medical school?

还是后来才想清楚的？我感觉可能是潜在的。我一直知道自己对神经科学这个广义领域很感兴趣。但直到医学院才真正接触这个领域。我记得很清楚，第一年有位神经解剖学教授黛安·罗尔森，她是个极其善良的人，在我们学习时对我非常耐心。

Or did you figure it out well there? I had a sense it was probably latent. I always knew that I was really interested in neuroscience, the general field. It wasn't until I was in medical school that I was actually exposed to it. And I remember really clearly in my first year, I had this neuroanatomy professor, Diane Rawlson, who was really an incredibly kind person, who was patient with me as we were learning.

你可能记得医学院要学习数百个不同的大脑解剖部位。这些我现在都忘了。只知道脑干大概在某个位置。大概在...是的。这就是我们医学院的仪式之一，学习所有那些术语和位置。

You probably remember in med school, like learning hundreds of different parts of the brain anatomy. All of which I've forgotten. I know there's a brain stem somewhere in there. There's somewhere something like Yeah. So that's part of our ritual, right, in medical school to learn all of those terms and locations.

但如你所知，某些老师就是能带来巨大改变。有一天她带我去手术室，我看到当时的一位导师——我当时只是个学生，但他后来成了我的导师——伯杰医生正在为一名胶质母细胞瘤患者做清醒手术。手术本身我觉得很有趣。但让我惊叹不已、以至于好几天难以入睡的部分，是亲眼看到了暴露的大脑，看到了皮质的样子。

But as you know, certain teachers just make such a huge difference. She took me to the Operating Room one day, and I saw one of my mentors at the time, I was just a student, but he ultimately became my mentor, Doctor. Berger, doing awake surgery on a patient with a glioblastoma. The surgery itself, I thought, was pretty interesting. But the part that left me awestruck and the part that basically made it very hard for me to sleep for a couple days was really just seeing an exposed brain, what the cortex looks like.

大脑皮层是大脑的最外层。它会搏动，会移动。但这些并非源自大脑自身的机械运动，而完全是由于呼吸、心率等因素造成的。

The cortex is the outermost part of the brain. It pulsates. It moves. But those are not from the mechanics of the brain itself. Those are all just from the breathing and the heart rate, etcetera.

血液在其中流动。真正让我震撼的是，看到病人说话时虽不能完全理解，却对大脑这一区域必须进行的复杂运算感到敬畏。这不像是在看一台电脑，你看到的本质上是一个由生物细胞组成的器官——准确地说，人类大脑拥有860亿个神经元。那个场景深深激励了我，让我彻底着迷。

The blood flow is coming through. So the thing that really struck off for me was seeing a patient talking and not fully comprehending, but really being in awe of the computations that must be happening in this part of the brain. And it's not like you're looking at a computer. You're looking at essentially an organ composed of biological cells, 86,000,000,000 to be precise, of how many neurons there are in the human brain. So that scene to me was deeply inspiring, and I was basically hooked.

我如此着迷，以至于当时并不真正明白自己选择的是什么，因为随后的培训相当艰难——我必须说，长达七年。但这一切都是值得的。我热爱其中的每一分钟，当然现在仍在学习。我们正处在神经外科的一个新转折点，即理解人类大脑的工作原理。

I was so hooked that I didn't really understand what I was signing up for because the training for it after that was pretty difficult. I have to say seven years. But it was worth it. I love every minute of it and I'm still learning, of course. Whereas at the very beginning of a new inflection point in neurosurgery, which is understanding how the human brain works.

你在住院医师期间有过顿悟时刻，对吗？嗯，我认为顿悟在于我们拥有这种获取信息的特权途径，即我们所谓的脑部映射。我们进行脑部映射是为了精确定位，比如处理脑肿瘤或引发癫痫的大脑病灶。通过映射，我们可以标出对语言或手臂运动能力至关重要的区域。

There was an epiphany you had at some point in residency, wasn't there? Well, I think there's an epiphany about we have this access, really privileged access, to use the information, what we call brain mapping, basically. We do the brain mapping because we want to be very precise about how we're approaching, for example, a brain tumor or a spot of the brain that's causing seizures. And we do the brain mapping so that we can map out the areas that are really important for language or the ability to move your arm. That's what we call the brain mapping.

我们识别这些区域是为了在手术中保护它们，同时实现最大程度的切除，如之前讨论的。切除的肿瘤越多，生存期越长；切除的癫痫区域越多，治愈的可能性越大。但神经外科手术总有代价，可能是瘫痪或失语症，即丧失说话能力。

And we want to identify those areas so we can protect them during the surgery. At the same time, do the maximal resection, like we spoke about earlier. The more that we can remove the tumor, the longer the survival. The more that we can remove of the seizure zone, the more likely someone is going to be cured of their epilepsy. But in neurosurgery, there can always be a cost, and that cost would be paralysis or aphasia, which is a condition where you lose the ability to speak.

我们总是在权衡：多切除几毫米是否值得？在许多情况下，这些至关重要的决定必须在手术室中当场做出。脑部映射帮助我们做出判断。过去，沃尔特·彭菲尔德在一百五十年前或一百二十年前使用电刺激器作用于皮层，在患者尝试说话或移动时暂时激活或干扰特定脑区功能，这是传统的映射方法，也是我们至今仍使用的技术之一，以确保手术安全。

We're always trying to balance, is it worth it to go that extra couple of millimeters versus not? And in many cases, these are really profoundly important decisions that have to be made right then and there in the operating room. And brain mapping is a way that we figure this out. In the old days, Walter Penfield, one hundred and fifty years ago, one hundred and twenty years ago, would use an electrical stimulator and would apply it to the cortex, and that will temporarily activate or disrupt the function of a specific part of the brain while someone is trying to speak or move, and that's traditionally how we've done mapping. And that's one of the tools, the techniques we still use today in order to make sure our patients are safe during these procedures.

我在住院期间的一个启示是，我们可以做的远不止用电刺激器进行映射。我们开发了记录大脑活动的技术，不仅能进行映射，还首次为我们提供了理解神经元工作原理的窗口，比如它们如何传递词语信息——就像我们正在进行的对话。你的大脑颞叶（位于双耳上方）中有一个区域，特别是左颞叶（如果你是右撇子，99%的右撇子语言功能主导区在左侧）。

One of the revelations I had during residency, of course, is that I think we can do a lot more than just applying stimulators to do the mapping. We've developed technologies to record from the brain that allows us to not only do the mapping, but also is really the first window that we have of understanding essentially how neurons work, how they convey information about words, for example, like in the conversation we're having. There's a part of your brain in the temporal lobe, which is right above your ear on both sides. The one on the left in particular, you're right handed. So ninety nine percent of right handers are dominant for language on the left side.

颞叶中有一个位置，就在你左耳上方约两厘米处。它正在处理我现在对你说的所有词语。因此，我们不仅利用这项技术来绘制这些关键功能的地图。可以说，大约十到十五年前的科学水平就是弄清楚这些功能在大脑中的位置。而现在，通过新技术的逐步演进，我们将科学推向了理解这些区域如何工作的层面，以获得越来越高的分辨率。

And there's this one spot in the temporal lobe, which is just about two centimeters above your left ear. That's processing all the words that I'm speaking to you right now. And so we've used this technology not only to map those critical functions. That's where the science was, I would say, about ten or fifteen years ago, figuring out where these functions are in the brain. And now we've moved the science to understanding how those areas work by a progressive evolution of new technologies to get us to higher and higher resolution.

我的意思是，我们可以测量细胞和细胞群的神经活动，然后将它们与不同的辅音和元音等联系起来。这确实是人类神经科学中一个极其激动人心的发展。我想回过头来，让大家了解一下清醒手术是如何进行的。因为传统的手术方式需要全身麻醉。而全身麻醉通常需要三个条件。

And what I mean by that is we can measure the neural activity of cells and cell populations and then link them to, for example, different consonants and vowels. And that's been really an extremely exciting development in human neuroscience. I want to back up and just have people understand how you even do awake surgery. Because the traditional way that surgery is done requires general anesthesia. And general anesthesia typically requires three things.

它需要一种药物来减轻疼痛，另一种药物来阻断记忆，还有一种药物来使你麻痹。当然，如果出现问题——也确实发生过——有时患者被麻痹了，但他们能感觉到疼痛却无法表达。这些是麻醉中发生的灾难性但所幸非常罕见的事件。但正确的麻醉是让患者没有时间感或任何记忆，他们感觉不到任何东西也无法移动，这意味着他们实际上是安全的。这也是为了保护他们。

It requires one type of medication to blunt pain, another type of medication to block memory, and another type of medication to paralyze you. Now, of course, if things go wrong and things have gone wrong, sometimes patients are paralyzed but they feel pain but they can't communicate it. And these are these catastrophic but fortunately very rare events that occur in anesthesia. But correct anesthesia is done where a patient has no sense of time or memory of anything, they can't feel anything and they can't move, which means they're actually safe. That's to save them as well.

请帮助我们理解，在没有这三个条件全部满足的情况下，你是如何进行手术的。就像我一开始说的，这是一种极端的医学形式，极端的手术形式。简而言之，能够实现的原因是大脑本身没有任何疼痛感受器。所以疼痛感受器实际上存在于我们的神经中，存在于头皮中，遍布我们的全身。这些实际上是我们感知疼痛和触觉的方式。

Help us understand how it is that you can do surgery without all three of those conditions being present. Like I said in the beginning, this is an extreme form of medicine, extreme form of surgery. And the way that, in a nutshell, it can be done is the brain itself doesn't have any pain receptors. So the pain receptors are the ones that are in our nerves, that are in the scalp, that are throughout our body. These are actually the way that we perceive pain and touch.

我想这对许多人来说起初是矛盾的，但大脑本身——它在处理身体传来的信息——实际上自身并没有那些感受器。所以我们通常的做法是麻醉头皮。我们使用像你去牙医诊所时用的东西，比如利多卡因。我们可以在切口周围注射。顺便说一下，骨头本身也没有任何疼痛感受器。

I think it's paradoxical to many people at first, but the brain itself, which is processing that information in the body, actually doesn't have those receptors itself. So the way that we typically do this is to numb the scalp. We use things like when you go to the dentist office, like lidocaine. We can inject around the site of the incision. The bone, by the way, doesn't have any pain receptors itself either.

大脑顶部我们称之为硬脑膜的膜确实有一些疼痛感受器，所以有时我们需要在那周围小心处理，并在硬脑膜周围进行一些局部麻醉。有趣的是，脑组织本身没有。还有一些其他区域，比如血管周围，可能会比较敏感。硬脑膜是敏感的。所以存在一些敏感区域，但它们可以被麻醉。

The membrane on top of the brain that we call the dura does have some pain receptors, so sometimes we have to be sensitive around that and do some local anesthesia around the dura. And interestingly, the brain tissue itself doesn't. There are some other areas, like around the blood vessels, that can be sensitive. The membrane, the dura, is sensitive. So there are areas, but they can be numbed.

因此，这是一个非常重要的事实，使我们在必要时能够进行这些清醒手术。所以病人被推进手术室，我见过这些，但我一时想不起确切步骤了。所以病人被推进手术室，他们没有插管。对吧？对吗？

And so this is a really important fact that allows us to do these surgeries awake when it's necessary. So the patient is rolled, and I've seen these and I'm just, I'm blanking on exactly the procedure. So the patient is rolled into the OR, they're not intubated. Right. Correct?

而且他们在这个过程中从未被插管。是的。这是一个躺在那里的完全清醒的病人，没有气管插管。对。也许为了舒适会插个导尿管？

And they're never intubated during this. Yeah. This is a patient who is laying there wide awake, no endotracheal tube. Right. Maybe a Foley catheter for some comfort?

是的，导尿管。好的。嗯。通常导尿管并不那么舒服。确实。

Yes, Foley catheter. Okay. Yeah. And usually Foley's are not that comfortable. Exactly.

但主要是为了在手术过程中监测尿量。你从做切口开始，我的意思是，先标记出你想切口的位置，然后就像做局部麻醉一样操作，就像切除脂肪瘤那样。你只是在头皮上涂抹利多卡因和肾上腺素。用电凝止血直到需要到达的位置。一旦到达骨头，你就可以开始钻孔，并在孔之间锯开。

But primarily so that we can monitor urine output during the surgery. You begin by making your incision I mean, drawing where you want to make your incision and then literally just doing this as though it's a local like you're having a lipoma removed or something. You're literally just covering the lidocaine and epinephrine across the scalp. You're bovying down to where you need to go. Once you get to the bone, you can start to literally put a hole in and start to saw across your holes.

是的。再补充一点细节，通常头部是固定的，所以不是像有人坐在椅子上我们在他动来动去时做这个，而是我们有一个固定头部的头架。病人有一定程度的镇静，然后你可以抬起。完全正确。所以我们采用轻度镇静。比如异丙酚之类的？

Yeah. Just to add a little bit more detail to that, which is that usually the head is fixed, So it's not like someone sitting in a chair and we're just doing this while they're moving around, but we have a head holder that fixes the head. The patient is somewhat sedated and then you can lift the Exactly right. And so we do a light level of sedation. Like propofol or?

像异丙酚，但剂量非常非常低。所以不是全身麻醉的剂量。是非常非常轻的剂量。派对剂量。这样麻醉师可以在你说‘嘿’的时候停止，因为我们可能需要一个小时才能进入。

Like propofol, but at much, much lower dose. So it's not a general anesthesia dosing. It's a very, very light dosing. The party dose. And that way it allows the anesthesiologist to stop it when you say, Hey, because we might need an hour to get in.

在那个时候，他们处于迷糊状态是可以的，但一旦我们需要进入内部，我就希望停止。绝对。病人在手术中真正清醒的时间通常只有一两个小时，即使手术长达六或八小时。主要是为了舒适，我们在最开始会进行镇静。然后会关闭镇静让病人完全清醒。然后你可以增加镇静来完成手术并再次关闭，整个过程都像结肠镜检查的水平，而不是全身麻醉的水平。那是全身麻醉对吧。

At that point, it's okay for them to be in La La land, but then I want it off once we have to get inside. Absolutely. The period that someone is actually awake during the surgery is usually only an hour or two, even if the surgery is like six or eight hours long. And primarily for comfort, we'll do sedation at the very beginning. We'll have the sedation turned off so the patient can be fully awake And for the then you can ramp up the sedation to finish the procedure But and close again, it's all done at the level of a colonoscopy, not the level of That's general right.

是的。再次，我们在播客前聊过，我在普外科的第二个月做了神经外科，意思是轮转过。让我震惊的一件事是，这听起来可能有点傻，但当你看着教科书，研究 homunculus（大脑皮层功能定位图），看着所有的血管系统，然后你实际看大脑时，它就像任何其他器官一样。就有点平淡。就像第一次看胰腺一样。

Yeah. Again, we were talking before the podcast how my second month of general surgery, did neurosurgery, meaning we rotated through it. And one of the things that blew my mind was how It sounds silly, but when you look at textbooks and you study the homunculus and you look at all of the vasculature and then you actually look at the brain, it's just like any other organ. It's just kind of a blah. It's like looking at the pancreas for the first time.

你可能会想，就这样？我怎么知道所有东西的位置？我想区别在于，可能身体上没有哪个部位的“地产”如此重要。比如你在做心脏手术时，能清楚看到自己在做什么，你知道左前降支动脉在哪里。

You're like, that's it? How do I know where everything is? I guess what makes it different is there's probably no part of the body where the real estate matters so much. When you're operating on other parts of the body, for example, if you're operating on the heart, you can really see what you're doing. You know where the left anterior descending artery is.

你知道堵塞的位置。尽管这是技术非常复杂的手术，但解剖结构是完全清晰的。我第一次看神经外科手术时，最让我震惊的是他们到底怎么知道自己在做什么？比如我们刚才切掉了多少亿个细胞？这显然从功能角度印证了你所说的。

You know where the occlusion is. And even though it's very technically complicated surgery, there is complete anatomic clarity of what is happening. I think the thing that struck me the most the first time I saw neurosurgery was how the hell do they know what they're doing? Like how many billion cells did we just lop off there? And obviously this speaks to what you're talking about from a functional standpoint.

但很多时候你并不需要那样。所以如果病人有脑膜瘤或其他肿瘤，你如何权衡这种取舍？你会不会说，看，有些地方你绝对不希望长肿瘤。比如就在我左耳上方，那里切除会非常困难，因为“地产”太宝贵了，我们可能会建议做清醒开颅手术来引导。

But a lot of times you're not doing that. So if a patient has a meningioma or some other tumor, how do you bracket that trade off? So do you sort of say, look, there are places where you never want to have a tumor. For example, right above my left ear. That would be a really difficult place to have to resect because the real estate is so precious and that's where we're going to probably recommend doing an open awake procedure to help guide us.

你是这样运用的吗？完全正确。所以“地产”至关重要，这都说得太轻了。但话说回来，那里有些非常昂贵的“地产”，也有些相对便宜的。

Is that how you're using that? That's exactly right. And so the real estate is critical. That's an understatement. But that being said, there are some really expensive real estate in there, and there's also some cheaper real estate.

但我想这就是我的观点，Eddie。这就像在跟我说曼哈顿的情况。是的，曼哈顿没有便宜的地产。有些地方每平方英尺要1万美元，但可能没有低于4000美元的。有个流行说法认为我们只用了大脑的10%。

But I guess that's my point, Eddie. It's like, that's sort of like telling me about Manhattan. Yeah. Like, there's no cheap real estate in Manhattan. There happen to be areas that are $10,000 a square foot, but there's probably nothing less than 4 So thousand a square there's this popular idea that we only need 10% of our brain.

我相信你听过这个。我听过，但不知道它什么意思。听起来像是胡扯。对。那可能是指维持生命。

I'm sure you've heard this. I've heard this, and I don't know what it means. It sounds like malarkey to me. Right. That might mean to stay alive.

要呼吸，你可能只需要10%的大脑。所以它真正的意思是，大约10%到15%的大脑对我们基本功能至关重要，比如移动、说话、看东西等。实际上远不止这些。但这也说明了我们大脑有些部分与其他部分存在高度冗余，比如额叶。

To respire, you might only need 10% of your brain. So what it really means is that there is maybe about 10% or 15% that is very critical for our basic functions, our ability to move, to talk, to see, etcetera. It's actually a lot more than that. But it's also referring to this point that there are parts of our brain, actually, that are extremely redundant with other parts of the brain. So the frontal lobes, for example.

我们在那里常规进行手术，很多时候人们确实没有受到影响。即使在判断力方面，甚至在...绝对是的。因为我们总是认为额叶是我们执行功能和我们能力所在的地方。我们总是开玩笑，比如我医学院的一个朋友，我们说他没有额叶。确实如此。

We do surgeries there routinely and oftentimes people really have no effect. Even in terms of judgment, even in terms of Absolutely, yeah. Because we always think of the frontal lobe as where we have sort of executive function and where we have the ability. We always joke, like one of my friends in med school, we said he had no frontal lobe. Exactly.

他就是忍不住说最不合适的话。别误会。额叶实际上对执行决策、冲动控制等有很多关键功能。但我的意思是它是冗余的，意味着额叶的不同部分实际上有相似的目的和相似的作用。因此，在大多数情况下，我们的许多患者可以承受相当大的手术，有时甚至切除整个额叶。

He just couldn't stop saying the most inappropriate things. And don't get me wrong. The frontal lobe actually has a lot of critical function for executive decision making, impulse control, etcetera. But my point is that it's redundant, meaning that different parts of the frontal lobe actually have similar purposes and similar role. And so for the most part, a lot of our patients can accommodate a fairly large surgery, sometimes even removing the entire frontal lobe.

两侧？不，不是两侧。真的，通常这些病变只在一侧。如果你从左或右侧切除整个额叶，会有实质性差异吗？我已经做过很多次了，让你知道。这真的取决于具体情况和场景。

Both sides? No, not both sides. Really, usually these pathologies are only on If one you took the entire frontal lobe from the left or right side, would there be a substantial difference? I've done that many times, just so you know. And it really depends on the case and scenario.

如果某人那里有一个缓慢生长的东西，并且大脑有时间进行重组，我们称之为可塑性，那么许多这些功能基本上将不再位于那个右额叶，而是转移到了左侧。哇。这是通过什么机制发生的？时间和功能，意味着这些事情不是一夜之间发生的。它们有时需要几周甚至几年的时间。

If someone's been having something that's slower growing there and there's been time for the brain to reorganize, what we call plasticity, a lot of those functions will essentially no longer be in that right frontal lobe and they've moved to the left side. Wow. What is the mechanism by which that happens? Time and function, meaning these things don't happen overnight. They take sometimes weeks and years.

但基本上，发生的事情是一些神经元随着时间的推移而丢失，然后其他神经元会在功能上进行补偿。但这实际上是如何发生的？所以假设我们在左额叶有一个缓慢生长的病变。左额叶是如何与右额叶沟通的？说，嘿，这些神经元正在受到损害。

But basically, what happens is some neurons get lost over time, and then others will compensate in terms of that function. But how does that actually happen? So let's posit that we have a slow growing lesion in the left frontal lobe. What is the left frontal lobe doing to communicate with the right frontal lobe? To say, hey, these neurons are being compromised.

它们的功能正在恶化。你们需要接手这些工作。这个信息是如何传递的？部分原因是，对于大多数人来说，额叶的两个部分大部分时间都在执行功能。所以这不仅仅是传递信息。

Their function is deteriorating. You guys need to pick up the slack. How is that message being transmitted? Part of it is that both parts of the frontal lobe for people, most people, are both doing the function most of the time. So it's not like it's just transferring the information.

而是两侧最初都参与了这些功能。然后一侧变弱，另一侧必须接手这些工作。在细胞水平上，这就是我们所说的突触可塑性。这些权重本质上构成了我们是谁。这些只是神经元用来相互沟通的权重。

It's that both sides were originally involved in those functions. And then one side gets weaker and the other one has to pick up that slack. At a cellular level, this is what we call synaptic plasticity. The weights essentially make up who we are. These are just the weights that neurons use to communicate with one another.

我们所有的学习都是为了塑造神经元相互接触处突触的权重。这是可以发生的，并且在我们的一生中都可以改变。每当我们学习一个新词时，就会形成以前从未有过的新突触、新连接。确切地说，从左到右，有一个我们称之为胼胝体的结构。

All of our learning is towards shaping that weighting of synapses that occur where neurons touch each other. And that can happen. That can change throughout our life. Every time we learn a new word, those are new synapses that have formed that were never there, new connections. Precisely from the left to the right side, there is this structure that we call the corpus callosum.

它是一个信息高速公路，连接着我们大脑的左右部分。诺贝尔奖得主罗杰·斯佩里曾进行过非常了不起的早期实验，描述了接受过胼胝体切开手术的患者，在某些情况下会出现一种现象，即患者基本上像拥有两个功能正常但彼此不沟通的大脑。因此，确实需要这两个正在重组区域之间存在这种连接。那么除了癫痫，还有什么原因会切断胼胝体呢？这确实是我们进行该手术的主要原因。

It's an information highway that connects the left part of our brain from the right side. There was a Nobel Prize, Roger Sparey, who'd done really incredible early experiments describing patients who had surgeries where you split that, and in certain instances you have this phenomena where people essentially like have two functioning brains, but they're not communicating to each other. So it does require that there is this connection between the two areas where they're being reorganized. Now outside of epilepsy, why else would the corpus be severed? That's really the main one that we use it for.

你能描述一下接受这种手术的患者如何表现吗？这非常引人入胜。有一种我们称之为分离综合征的现象。如今，患者接受这种手术的临床指征、医疗指征是：一些患有癫痫发作的患者会出现严重的发作，他们会倒下，我们称之为跌倒发作。通常这意味着癫痫发作在大脑中扩散得非常快，导致人们身体肌张力丧失，然后基本上就会摔倒。

Can you describe how patients that undergo that procedure behave? It's very fascinating. So there's a phenomenon that we call a dissociation syndrome. The clinical indication, the medical indication for why someone would undergo this nowadays is that some patients with seizures have severe seizures where they fall down, what we call drop attacks. And usually what that means is that the seizure is spreading so quickly across the brain that people lose the tone in the body and then basically fall.

这之所以成为一个问题，即癫痫发作造成的伤害，是因为人们实际上会因此受伤。所以，患有这类癫痫发作的人一直戴着头盔并不少见，因为他们摔倒的风险非常高。这些是医学上难以控制的癫痫发作。它们无法通过任何程度的……没错，完全正确。

And why that becomes a problem, the injury of the seizures, is that people actually injure themselves. So it's not uncommon for people who have these kind of seizures actually to be wearing helmets all the time because they're at such high risk of falling. These are just medically recalcitrant seizures. They cannot be prevented with any degree of That's right. That's absolutely right.

我明白了。没有任何药物可以控制。尤其是这些发作并非由一个小点引起，而是整个大脑半球或象限的问题。但问题在于，癫痫发作的本质是大脑细胞群出现非常不受控制的同步活动。

I see. Without any kind of medication. And these are particularly ones that there's not one small spot that's causing the seizure. It's the whole half or quadrant of the brain. But the problem is what a seizure is, is basically when you have this very uncontrolled synchrony of a large mass of the brain cells.

所以，正常情况下，如果你想想大脑和其中的神经元，就像体育场里的人，他们正在进行各自的交谈。这就是大脑正常工作的方式。但是，假设突然之间所有人都在做人浪，进行某种高度协调的活动。所有那些正常的交谈现在都消失了。大脑现在被另一种现象所劫持，一切都变得非常协调。

So normally, if you think about the brain and the neurons within the brain, it's like people in a stadium, they're having their individual conversations. That's the way the brain normally works. But let's say all of a sudden everyone's doing a wave and something hyper coordinated. All of those normal conversations are now gone. The brain has now become hijacked by this other phenomenon where everything has become very coordinated.

这就是人们失去意识的原因，因为所有正常功能基本上都停止了。而这种同步化可以通过其连接性实现。每个细胞都连接到相邻的细胞，并且每个细胞都通过像连接左右脑的胼胝体这样的结构与大脑中的所有其他细胞相连。因此，当出现这种高度同步时，人们几乎可以瞬间失去意识。所以，历史上发明胼胝体切开术的最初原因之一，就是为了切断左右半球之间的联系。

That's why people lose consciousness because all the normal function is basically shut down. And the way that it can become synchronized is through its connectivity. Every cell connecting to its adjacent cell, and every cell connected to all the other cells in the brain through the things like the corpus callosum that connects left to the right. And so when you get that hypersynchrony, people can essentially lose consciousness almost instantaneously. So one of the reasons historically why the corpus callosmia was invented in the very first place was to sever the connection between the left and right hemisphere.

这并不能阻止癫痫发作，只是限制了其扩散。完全正确。它不停止癫痫发作，但作用是阻止癫痫的传播，即癫痫从一侧快速传播到另一侧。而一个人要失去意识，基本上需要双侧大脑半球的结构如丘脑都受到影响。

Which doesn't stop the seizure. It just limits the spread. That's exactly right. It doesn't stop the seizure, but what it does is stops the propagation, the very fast propagation of the seizure from one side to the other. And in order for someone to lose consciousness, you basically have to have both sides of the hemisphere structure like the thalamus.

基本上，为了保持意识，必须双侧半球都正常运作才能失去意识，或者丘脑等深层结构受损。因此，这类跌倒发作性癫痫会导致人们昏厥、摔倒，而一种能显著阻止这种情况的方法就是断开左右半球的连接。那么，除了希望他们的跌倒发作消失之外，这位患者的生活有何不同？现在左右半球断开连接后，它们的行为方式有何变化？如今我们做这种手术时，通常会断开胼胝体的前三分之二。

That's basically, in order to have consciousness, you have to have both hemispheres out in order to lose consciousness, or a deeper structure in the thalamus or something like that. And so these kind of drop attack seizures are ones that people blackout, fall, and one way you can actually dramatically stop a lot of that is disconnecting the left from the right hemisphere. And so how does that patient, how is their life different aside from the fact that hopefully their drop seizures are gone? What's the change in the way that their left and right behave now disconnected? Most of the time when we do this nowadays, we disconnect about the anterior two thirds of the corpus callosum.

我们通常不横断整个胼胝体的原因是因为人们可能会出现一些副作用，即我们所说的分离综合征，即左脑和右脑的活动基本上会出现分离。例如，某人右手感觉到的东西由左脑处理，而右脑完全不知道发生了什么。人们可以勉强应对这种情况，但这确实影响了他们的生活协调性。因此，如今我们尽量只处理前部，保留后部，以减少一些这类副作用。但这能解决最初的问题吗？

And the reason why we don't typically transect the whole corpus callosum is because of some of the side effects that people can have, it's what we call a dissociation syndrome, where you can basically have a dissociation between what the left brain is doing and the right brain. So for example, someone essentially feeling something on the right hand, which is processed by the left part of the brain, and the right part of the brain really having no awareness of what's going on. People can get by with that, but it does affect how they can get along. So nowadays, we try to just do the front part of it and leave the back part that helps reduce some of those side effects. But does it solve the initial problem?

癫痫的问题？是的。不，它不能治愈癫痫，但确实阻止了癫痫的传播，这样人们就不会失去意识。抱歉，通过保留后部三分之一仍然相连，它能防止癫痫跨半球传播吗？

Of the seizures? Yes. No. It doesn't cure the seizures, but it really just stops the propagation of the seizures so that people don't lose consciousness. Sorry, by leaving one third in the posterior still adjacent, it prevents the propagation across the hemispheres?

在非常多的情况下是的。如今在某些情况下，仍然需要进行全胼胝体切开术。这是一个非常精细的手术，因为连接左右半球的胼胝体并不位于大脑顶部，实际上——它非常深。非常深。所以要到达那里，实际上必须物理上分离左右半球。

In many, many cases. In some cases nowadays still, have to do a total calisotomy. It's a very delicate surgery because the corpus callosum that connects the left and the right, it's not sitting on the top of the brain, it's actually- It's very deep. It's very deep. So to get there, you actually have to physically separate the left and right hemisphere.

我们从顶部进行手术。我们做一个以中线为中心的颅骨切开术，但不能正好在中线上，因为那里有一条大的引流静脉叫做上矢状窦。所以我们必须选择左侧或右侧，然后非常小心地将左右分开，并通过那个狭窄的通道切断这些连接。正下方有什么防止你使用电刀时过热？哦，有一条血管沿着胼胝体顶部走行，这实际上是手术中最关键的部分，即我们分离那两条分支，那些胼周动脉。

We do that from the top. We do a craniotomy that's centered over the midline, but it can't be right over the midline because we have a large draining vein there called the superior sagittal sinus. So we have to either choose the left side or the right side, and then we have to very carefully separate the left from the right, and through that narrow corridor, transect those connections. And what's directly underneath it that prevents you from running that bovie a little too hot? Oh, well, there is a blood vessel that runs along the top of the corpus callosum, and that's actually the most critical part of the surgery is that we separate those two branches, those pericallosal arteries.

这些动脉非常重要，因为它们供应大脑的部分区域，即内侧额叶皮层，而其中一部分实际上是运动皮层，负责供应和控制我们的腿部。所以如果手术中出现中风作为副作用或并发症，那么某人可能会腿部瘫痪。所以这是一个有趣而精细的手术。看到胼胝体暴露出来真是令人惊叹，它闪闪发白。

Those arteries are really important because they supply the part of the brain, the medial frontal cortex, and the part of that that is part of the motor cortex actually is what supplies and controls our legs. So if you have a stroke, let's say, as a side effect or complication of that procedure, then someone would be paralyzed in the leg. So it's a fun, delicate surgery. It's amazing to see that exposure of the corpus callosum. It's glistening white.

这就是我们能看到它的方式，它与大脑皮层截然不同，因为它呈现出非常明显的白色。这种白色来自髓鞘。它是一个高度髓鞘化的结构，因为它以毫秒级的速度将信息从左脑传递到右脑，是一种超高速连接。你是否曾从哲学角度思考过，通过胼胝体完成一次完整的信息交换似乎能产生两个人，这对人类意识意味着什么？没错。

That's how we can see it, and it's very distinct from the cortex because it's really clear white. That white comes from the myelin. It's a heavily, heavily myelinated structure because it's conveying information from the left side of our brain to the right side on the order of milliseconds, a super fast connection. Do you ever think philosophically about what the implications are for human consciousness by the fact that you can do a complete transaction of the corpus and seemingly produce two people? That's right.

或者可能是两个意识。是的。这意味着什么？我认为这回到了一个更棘手的问题：你如何定义意识本身？这里存在着很多哲学上的争论。

Or potentially two consciousnesses. Yeah. What does that mean? Well, I think that goes back to a harder question of how do you define what consciousness is in the first place? And this is where there's a lot of philosophical debate about that.

你会为这些争论困扰吗？其实不会。我不能，因为我无法理解它。是的。这超出了我的能力范围。

Do you trouble yourself with such debates? Mean Not really. I can't because I can't wrap my head around it. Yeah. It's above my pay grade.

我确实会从临床实践的角度思考它，而不是哲学角度。临床问题更像是，患者是否处于昏迷状态，为什么，以及我们如何让他们从创伤性脑损伤、某些中风、癫痫等中恢复。我们每天都在从这个角度思考意识问题。但从哲学角度，我不会为此失眠太多。我会稍微失眠一点。

I do think about it from the practical clinical perspective, not so much the philosophical. The clinical one is like, is a patient in a coma or not and why and how do we get them out of that traumatic brain injury, certain strokes, epilepsy, etc. We think about consciousness from that perspective literally all the time every day. But from the philosophical, I don't lose a lot of sleep over that one. I lose a little bit of sleep over it.

我们来谈谈脑机接口。你已经提到过它。我希望这么说不会冒犯到别人，但如果我们坦诚相待，至少应该承认迄今为止医学在治疗神经退行性疾病方面表现平平。所以无论是阿尔茨海默病，还是其他非退行性痴呆，我们谈论帕金森病、卢伽雷氏病。我的意思是，我们似乎就是无法治疗这些疾病。

Let's talk a little bit about the brain computer interface. You've mentioned it already. I hope I'm not insulting people when I say this, but if we're going to be brutally honest, we should at least acknowledge that medicine to date has been pretty unimpressive when it comes to treating neurodegenerative disease. So whether we're talking about Alzheimer's disease or even other non degenerative forms of dementia, We were talking about Parkinson's disease, Lou Gehrig's disease. I mean, we just don't seem to be able to treat these diseases.

所以无论我们用什么药物治疗这些疾病，也许在帕金森病的情况下，我们可以稍微延缓进展。但你同意这种评估吗？即传统治疗这些疾病的方法基本上是不成功的？我大体上同意，但需要补充的是，我认为在理解疾病机制方面取得了很大进展。由此，我认为有很多有希望的治疗方法。我一般同意，在神经学和神经外科传统上，治疗确实旨在阻止病情恶化或减缓进展。

So whatever medications we throw at these things, maybe in the case of Parkinson's disease, we can delay progression a little bit. But would you agree with that assessment that the traditional approach to treating these diseases has been largely unsuccessful? I would largely agree with the caveat that I think a lot of progress is being made to understand what's going on. And from that, I think there's a lot of promising therapies. I would generally agree that within neurology and neurosurgery traditionally, therapy has really been designed to stop things from getting worse or slowing progression.

直到最近，功能替代才真正成为可能。是的。我想从你那里了解的是，因为我认为你比任何人都更了解这一点，或者至少在了解最多的人之列，我们是否需要从工程角度重新审视这些疾病的治疗方法，而不是从外周给药的角度？所以治疗疾病的传统方法是药物。你注射、服药、服用某种东西，希望有足够的药物穿过血脑屏障，开始治疗当前的病症。

Replacing function has never really been possible until very recently. Yeah. I guess what I want to understand from you, because I think this is something that you know more about than anyone, or certainly among the people who would know the most about it, is do we need to revisit our approach to these diseases more from an engineering perspective than from a peripherally administered medication perspective? So the traditional approach to treating disease would be medication. You take an injection, you take a pill, you take something and you hope that enough of it gets across the blood brain barrier and it starts to treat the condition at hand.

但是，看着帕金森病患者——这是一种运动功能障碍疾病，诚然源于中枢神经系统——很难不至少认为这是一种功能性问题。为什么没有，或者是否存在一种工程学方法可以应对这个问题？这是个好问题。让我这样来说吧。药物将始终是一个非常重要的目标，不仅是为了减轻症状，更希望能找到治愈方法。

But it's hard to look at a patient with Parkinson's disease, which is a motor defect disease, admittedly that stems from the CNS, and not at least think this is a functional condition. Why isn't there, or is there, an engineering approach that could be taken to this? It's a good question. And let me put it this way. Medications are always going to be a really important goal, not only to reduce symptoms, but hopefully find cures.

但还有另一大类正在兴起的疗法，它们与脑细胞的另一种特性有关，这种特性与，比如说，胰腺或肝脏非常不同。它是方程式的电学方面。所以有化学和生物学方面，但也有这个电学方面。大脑是一个电学器官。我们的思维确实依赖于这些发生在单个神经元及其集合中的电化学过程。

But there's this whole other class of therapies that are coming online that have to do with this other property of brain cells, which is very different than, let's say, the pancreas or the liver. It's the electrical side of the equation. So there's the chemical and biological side, but then there's this electrical side. And the brain is an electrical organ. Our thoughts are really dependent on these electrochemical kind of processes that happen at individual neurons and the collection of them.

因此，有一个庞大且不断发展的领域，我们称之为神经工程学，它正试图利用计算机、传感器、芯片来解释、窃听神经元之间如何相互传递信号，而不管它们的病理或生物学特性如何。而是，它们到底在彼此说什么？我们能窃听到吗？我们能解释它吗？我们能解码它吗？

So there's this large and growing field that we call neuroengineering that is really trying to use computers, sensors, chips in order to interpret, eavesdrop on how the neurons are signaling to each other, regardless of their pathology or the biology. But just what are they saying to one another? Can we eavesdrop on that? Can we interpret it? Can we decode it?

然后，更重要的是，我们能否利用这些信息来引导更正常的信号传递？这之所以可能重要，是因为归根结底，功能来自于那种电活动。是神经元动作电位的传播，才产生了我们的思想、我们的沟通能力、我们行走和移动手臂的能力。没有它，这些就不存在。所以我认为神经工程学是生物学或药物学方法的一种补充。

And then, more importantly, can we use that information actually to guide more normal signaling? Why this is potentially important is that at the end of the day, the function is from that electrical activity. It's the propagation of those action potential by neurons, which gives rise to our thoughts, our ability to communicate, our ability to walk, move our arm. Without that, it's not there. So I would say neuroengineering as a complement to the biological or pharmaceutical approaches.

埃迪，如果你和我被同时映射在一起，这个问题甚至可能没有意义。所以请随意调整问题使其合乎逻辑。但我想你会明白我想问什么。我大脑的所有电活动都可以被映射到计算机上，你的也可以。并且我们在想着同样的事情。

Eddie, if you and I were mapped simultaneously together, this question might not even make sense. So please feel free to adjust the question to make it logical. But I think you'll understand what I'm trying to ask. All of the electrical activity of my brain could be mapped to a computer and the same could be done with yours. And we were thinking the same thing.

所以这是一个实验，我们俩都被要求想同样的事情。彼得，埃迪，我们希望你们俩都想想坐在海滩上，双脚埋在沙子里。天气很热。尽可能描述得详细，计算机屏幕上的输出会相似吗？计算机能识别出相似的电输出吗？

So it was an experiment where we were both told to think the same thing. Peter, Eddie, we both want you to think about sitting on a beach with your feet in the sand. It's hot. As descriptive as you want it to be, would the outputs on the computer screen be similar? Would the computer be able to appreciate similar electrical output?

或者说，两个尽力想着同样事情的人，是否也无法产生相同的输出？换句话说，思想与电活动之间存在一一对应的映射关系吗？简短的回答其实是两者皆有。所以在你举的那个例子中，如果我们俩都在看同一张海滩场景的图片，是的，我们大脑的同一部分——我们称之为枕叶的大脑最后部——将会处理那些图像。初级视觉皮层将会把那个空间解析成我们所谓的视网膜拓扑空间，本质上就像是图像中不同像素所在的位置。

Or could two people that are doing the best job they can to have the same thoughts not be able to produce that? In other words, is there a one to one map of thought to electrical activity? Short answer is actually both. So in that example that you gave, if both of us are looking at the same picture of a scene on the beach, yes, the same part of our brain is going to be processing those images in the very back of the brain that we call the occipital lobe. The primary visual cortex is going to be parsing that space into what we call retinotopic space, like essentially where those different pixels are located in the image.

那部分将高度保守，不是完全相同，但在你我大脑之间高度相似。当这些计算进一步向上游推进时，它们会变得更加分化，更具体于我们各自的大脑，实际上更依赖于我们的历史——思想史、个性，以及一切与大脑其他部分互动的东西。我给你举个很好的例子：你听西班牙语、法语或德语的方式，与那些母语人士会有很大不同。

That part is going to be highly conserved, not identical, but highly conserved between your brain and mine. It's where these computations go further upstream, where they become much, much more differentiated, much more specific to our brain, much more dependent actually on our history. History of thoughts, our personality, everything that's interacting with the rest of the brain. I'll give you a great example. The way that you may hear Spanish or French or German is going to be very different than someone who is a native speaker of those languages.

你的大脑会处理其中一些声音。你会听到它们，但不容易分辨出单词。或者，我听引擎声的方式与我妻子听引擎声的方式不同。绝对是的。我喜欢那声音。

Your brain is going to process some of those sounds. You'll hear them, but you're not going be able to pick out the words very easily. Or the way I hear an engine versus the way my wife hears an engine. Absolutely. Love the sound.

她对那声音有点恼火。我们听到的是同样的东西。绝对是的。所以有些部分会非常相似，比如我们如何处理一些感官属性。然后，你越深入系统，它就变得越定制化。

She's mildly annoyed by the sound. We're hearing the same thing. Absolutely, yeah. So there are parts that are gonna be very similar, like how we process some of the sensory attributes. And then the further you go deep into the system, the more it becomes very, very tailored.

其中一些是硬连线的。我们视觉系统的早期方式，很多都是硬连线。它深受我们所看到的影响。理论上，看到蛇应该自动产生负面反应，不需要学习，我猜进化可能已经为我们硬连线了这一点。

Some of this is hardwired. The way that our visual system early on, a lot of it is hardwiring. It's heavily influenced by what we see. Seeing a snake should automatically produce a negative response that doesn't have to be learned in theory, I assume. Evolution has probably hardwired us for that one.

有些东西是本能的。某些气味，我们天生就不喜欢那些闻起来腐烂或类似的东西。哦，是的。绝对是的。有很多这样的东西是非常直觉的。

There are some things that are instinctual. Certain odors, we'd be hardwired not to like things that are gonna smell rotten or something like that. Oh, yeah. Absolutely. There's a lot of those things that are very intuitive.

现在，回到我们给你看海滩图片的例子，你随时间变化有多大？所以如果我们在你10岁、20岁、30岁、40岁、50岁时做这个实验，那也会改变吗？它会改变，但变化较小。我认为随着时间的推移，这些事物会变得精炼，而实际上随着时间的推移，它们会失去精炼度。所以随着我们年龄增长，一些表征实际上变得不那么清晰。

Now, going back to the we're showing you the picture of the beach, how much do you change over time? So if we did that experiment when you were 10, 20, 30, 40, 50, would that also change? It will change, but less. I think over time, these things become refined, and over time, actually lose their refinement. So as we age, some of those representations actually become less clear.

如果我们以听力为例，随着时间的推移，人群中有很多人很难在拥挤的餐厅里，那里有很多背景噪音，竞争性的对话在进行，然而这些人可能有完美的听力。所以信号处理成了问题。完全正确。这本身不是耳朵的问题。

If we talk about hearing, for example, there are a lot of people in the population over time. It's very hard for them to be in crowded restaurant where there's a lot of background noise, competing conversations going on, and yet these individuals can have perfect hearing. So signal processing is becoming the problem. That's exactly right. It's not an ear problem per se.

这是一个感知问题，主要发生在大脑中。这与信息处理方式有关，比如信息的保真度是否预示着某些不好的事情？单独来看，并不是。但我们确实知道，当人们出现这个问题时，他们往往更加社交孤立。因此会产生很多次要影响。

It's a perceptual problem, and largely in the brain. And that has to do with how that information, like the fidelity of the that a harbinger of something bad? Independently, no. But we do know that when people have that problem, they tend to be more socially isolated. So there's a lot of secondary things that happen.

我们确实知道，当人们有听力损失却未被识别时——很多人确实存在未被识别的听力损失。人们没有充分意识到的是，如果你无法进行交流对话，你的大脑就接收不到这些信号。它正在被剥夺刺激。通过许多研究我们现在了解到，听力损失的认知影响实际上可能相当深远。它会加速与年龄相关的记忆衰退。

We do know that when people have hearing loss and it's unrecognized, a lot of people have unrecognized hearing loss. And what people don't fully appreciate is that if you don't have access to communication, to conversation, your brain is not getting those same signals. It's becoming deprived. And what we do know through many studies now is that the cognitive effects of that hearing loss actually can be quite profound. It accelerates age related memory loss.

实际上在我们实践中内部认为，这是导致认知衰退的原因。大约两年前有一项研究提出质疑，尽管该研究部分撤稿，方法论也存在一些缺陷。但据我所知，尚未有重复实验。关键问题当然是：如果你矫正听力损失，比如说随机选择一组早期轻度认知障碍患者并矫正其听力，能否纠正、预防或逆转病情？如果存在因果关系，理论上应该可以。

We actually internally in our practice believe that that is causal to cognitive decline. Now there was a study that came out about two years ago that suggested it wasn't, although the study had a partial retraction, the methodology was a little flawed. But to my knowledge, I don't know if it's been repeated. The question being of course is if you correct hearing loss, let's say you randomize a group of people with early MCI and you correct hearing loss, do you correct or prevent or reverse it? And again, if there's causality there, would expect that you would.

那视觉方面呢？随着人们年龄增长出现白内障等问题导致视力下降，是否同样会剥夺足够的神经刺激从而影响认知维持？或者因为不涉及语言问题所以影响较小？影响确实较小。而且我对视觉皮层年龄相关问题的普遍性了解不多。

What about with visual? As people get older and they develop cataracts or things of those nature and their visual acuity goes down, does it have the same effect on depriving them of enough neural stimulation to maintain? Or is it not as much because it's not a language issue? It's not as much. And I'm less aware in the prevalence of something that's age related, just in the visual cortex, for example.

让我们回到脑机接口。如果在派对上有人问这听起来很高科技，但到底是什么？好吧，我们来拆解这个术语。大脑指的是任何与皮层或深层结构交互的设备。

So let's go back to brain computer interface. How would you explain this to somebody at a party if they said, that sounds pretty high-tech, but what is it? Okay. Let's just break apart the terms. Brain refers to really any kind of thing that interfaces with the cortex or the deeper structures.

计算机是外部的数字设备。现在很多人简称其为BCI（脑机接口）。这个术语很混乱，因为它可能意味着很多不同的事物。简而言之，对大多数人来说，它指的是记录大脑信号的系统——无论是从头皮非侵入式记录还是大脑内部完全侵入式记录——并将这些信号连接到计算机进行分析处理。在多数BCI研究中，应用场景例如是移动电脑光标。

The computer is a digital device on the outside. A lot of people now call this BCI, brain computer interface for short. It's a very messy term because it could mean a lot of different things. I think in a nutshell, what it means is, for most people, a system that is recording from the brain, whether it's non invasive from the scalp or something that's fully invasive within the brain itself, and connecting those signals to a computer that analyzes the signal and then does something with it. In many cases of BCI research, the application is, for example, to remove a computer cursor.

或者像我们做的研究是为严重瘫痪无法说话的人替代言语功能。所以核心是解读脑信号，用计算机解析这些信号，然后转换成对我们有用的形式。在你举的例子中，你描述的是失语症患者无法说话？让我具体说明：我们很多工作对象是患有严重瘫痪的患者。

Or the research that we've done is to replace speech words for someone who's severely paralyzed and unable to talk anymore. And so it's about interpreting brain signals, and then using a computer to interpret those signals, and then transform them into a form that's useful to us. So in that example you gave, you're describing a patient with aphasia who can't speak? Let me be very specific about that. So a lot of the work that we've done is on people that have a severe form of paralysis.

失语症，我们通常指的是那些大脑语言中枢受损的人，比如中风患者。我们最近关注的是患有严重瘫痪的患者，如肌萎缩侧索硬化症（ALS）。这里的问题是，他们的语言能力基本正常，但无法将运动信号传递出来。无法将运动信号传递到声道、嘴唇、舌头、下颌和喉部。这些下行纤维受到ALS的严重影响。

And aphasia, we typically refer to as someone who's got, let's say, a stroke in the language centers of the brain. Where we've focused recently is on patients that have a severe form of paralysis like ALS. So there, the problem is they have largely normal language, but they can't get those Can't get the motor signal out. Can't get the motor signal out to the vocal tract, the lips, the tongue, the jaw, the larynx. Those descending fibers are severely affected by ALS.

它们会退化，这就是为什么患者逐渐瘫痪并失去说话能力。重要的是，他们虽然失去了说话能力，但认知功能仍然完好。是的。对于这样的个体，通过将计算机连接到他们的大脑，希望能够提取出他们想要表达的内容，并以书面草书文字的形式显示在电脑屏幕上？没错。

They degenerate, and that's why people progressively become paralyzed and lose ability to speak. An important part of that is that they lose ability to speak, but they still have full cognition. Yeah. And for that individual, by attaching a computer to their brain, you're able to hopefully extract in written cursive text whatever across the computer screen what they're wishing to say? That's right.

好的。我们来谈谈这可能如何实现。你之前提到至少有两种主要的方法来提取这些信息。一种是非侵入性的方法，可能是在头上贴满电极，就像我的头一样剃光。另一种是非常侵入性的方法，实际上是移除头皮，将这些设备直接放置在大脑皮层上。

Okay. Let's talk about how that could possibly be done. You mentioned earlier there are at least two broad ways to extract that information. A non invasive way where presumably you're putting electrodes all over a head that's as well shorn as mine. Alternatively, a very invasive way where you actually remove the scalp and you lay these things on the cortex itself.

对吗？是的。所以范围包括脑电图（EEG），即传感器直接放置在头皮上，进行非侵入性记录。你可以随时移除它们。而另一个极端则是将电极实际植入大脑。

Correct? Yeah. So the range would be EEG, which is where sensors are placed on the scalp directly, recording non invasively. You can remove them at any time. And then the far other extreme is electrodes that are actually placed into the brain.

大多数是ECoG。ECoG指的是放置在大脑表面的电极。这是 electrocorticography 的缩写，这也是我们实验室大部分工作的重点。它只是放置在大脑皮层表面，硬脑膜下的皮层上。完全正确。

Most ECOG. ECOG would be electrodes that are on the brain surface. That's short for electrocorticography, and that's where we've done the vast majority of our work in my lab. And that's just placed on the surface of the cortex, under the dura on the cortex. That's absolutely correct.

这样做的好处是，电极的植入不会对大脑本身造成损伤。记录随时间推移是稳定的。我们现在使用ECoG设备来帮助癫痫患者，例如，现在基本上可以有一个起搏器，从大脑表面记录信号，然后进行刺激以帮助停止癫痫发作。这是一个完全植入的设备吗？正在朝这个方向发展。

So what's nice about that is that you don't have the injury to the brain itself from the insertion of the electrodes. It's a stable recording over time. We now use ECOG devices to essentially help people with seizures, for example, where you can basically have a pacemaker now that records from the brain surface and then stimulates to help stop the seizures. And this is a fully implanted device? It's moving towards that.

因此，我们在临床试验中所做的工作是使用一个通过手术放置但通过端口连接的阵列。我们称之为经皮端口，因为它实际上是物理连接并固定在头骨上。大脑上的阵列穿过硬脑膜并固定在头骨中。端口从哪里伸出体外？就在头皮的顶部。

So the work that we've done in our clinical trial is using an array that's surgically placed but connected through a port. We call it a percutaneous port because it's actually physically attached and anchored to the skull. An array on the brain, it comes out the dura and is anchored in the skull. Where does the port exit the body? Right on the top of the scalp.

如何防止感染，尤其是在如此近距离的情况下。是的，这是个非常好的问题。这正是早期原型脑机接口（BCI）的主要问题所在。我们团队以及世界上其他一些团队正在使用类似的技术，主要是为了证明是否有可能将大脑活动编码用于实际用途。

How do you prevent infection with such a close Yeah. It's a really good question. And that's what the main problem with this early prototype BCI. And it's our group. There's other groups around the world that are using similar things primarily to show if it's possible actually to code brain activity for useful purposes.

所以目前该领域正在发生的情况是，许多这类技术将逐渐实现无线化。但你完全正确。主要原因之一是我们希望摆脱经皮的方式。我们希望摆脱那些除了其他问题外还存在感染风险的端口，转向完全可植入、完全无线的设备。你觉得距离实现这个目标还有多久？

So what's happening right now in the field is a lot of these technologies are now going to become wireless over time. But you're absolutely right. One of the main reasons is that we want to move away from the percutaneous. We want to move away from the ports, which are infection risks on top of other problems, and move to things that are fully implantable, fully wireless. How long do you feel you're away from that?

基本上大约一年。好的。我们已经为此工作了相当长一段时间。所以这是一个非常有趣的时期，我们看到电气工程、高带宽无线技术（其性能远超蓝牙）、先进电子技术等领域的能力正在汇聚，这些技术现在允许我们将一些传感器印刷在比一张纸还薄的基底上，体积非常非常小，并且这种基底能够贴合人类大脑皮层表面的褶皱、峰谷结构。那么，皮层脑电图（ECOG）和直接插入大脑的传感器之间有什么权衡？

Basically about a year. Okay. We've been working on it for quite some time. And so it's a really interesting time where we're seeing a convergence of, like, what's possible with electrical engineering, high bandwidth wireless, pressing way beyond what we can do with Bluetooth, advanced electronics that now allow us to print some of these sensors on a substrate that is thinner than a piece of paper, really, really small, and on a substrate that can conform to the convolutions, the different peaks and valleys of the human cortical surface. So what is the trade off between ECOG and sensors inserted directly in the brain?

分辨率差异是什么？嗯，这是一个非常重要的问题，我们和许多其他人目前正在努力弄清楚。大多数时候，当人们将电极放入大脑时，必须从中获得一些好处。通常这是为了记录更高的分辨率，通常是试图记录单个神经元、单个细胞的活动。你如何分离出一个单细胞？

What's the resolution difference? Well, that's a very important question that we and many other people are trying to figure out right now. Most of the time when people are putting an electrode into the brain, there has to be some gain for that. And usually that's for recording a higher resolution, usually trying to record the activity of single neurons, a single cell. How can you isolate a single cell?

非常小的电极。超级小的电极。我们在研究中对此做了大量工作。该领域面临的挑战一直是非常难以稳定地记录单个细胞超过几个小时或几天。所以这是一个挑战。

Really small electrodes. Super small electrodes. We do a lot of work with this in our research. The challenge for the field has just been that it's very hard to stably record from single cells more than a couple of hours or days. So that's one challenge.

另一个挑战是，当你将电极放入大脑时，它可能会引发反应。我们一开始谈到的那些胶质细胞，那些支持细胞，它们实际上也具有免疫功能。它们检测到有异物存在，就会激活并对其产生反应，在电极周围形成疤痕。所以，将电极放入大脑进行这种非常微观的记录的优势在于，你可以从单个细胞获得更精细的信号。缺点在于，它可能引发反应，随着时间的推移降低这些信号的保真度。

The other challenge is that when you put the electrodes into the brain, it can create a reaction. Those glial cells that we talked about at the very beginning, those support cells, they actually have immune function as well. They detect that there is a foreign body and they'll activate and they'll react to it, create a scar around the electrodes. So the advantage of having electrodes in the brain to do this very microscopic kind of recording is that you can get a finer signal from single cells. The disadvantage is that it can create a reaction that reduces the fidelity of those signals over time.

我们一直对在大脑皮层上使用这些传感器非常感兴趣的原因之一是，随着时间的推移我们了解到，如果电极没有穿透皮层表面的软膜（即覆盖皮层的最外层薄膜），如果你没有任何东西穿过它，你就可以避免许多那样的免疫反应，避免许多疤痕形成，保护下方的功能。但这是我们正在积极尝试理解的事情。所以，为了让我有个数量级的概念，如果头皮脑电图（EEG）的分辨率是1，一个单位，那么皮层脑电图（ECOG）是多少？植入电极又是多少？

One of the reasons we've been most interested in using these sensors on the brain cortex is that we've learned over time that if you don't have the electrodes penetrating through the peel surface of the cortex, that's the outermost very thin membrane that's covering the cortex. If you don't have anything going through that, you can avoid a lot of those immune reactions, avoid a lot of that scarring, preserve the function that's underlying. But this is something that we're actively trying to understand. So just to give me a sense of magnitude, if EEG on the surface is one, one unit of resolution, what would ECOG be? And what would implanted electrode be?

是一、十，还是一百？你设想的那个分辨率是在什么尺度上？嗯，如果从头皮开始，我们暂且随意地称之为一，然后想想你能用皮层脑电图（ECOG）做什么，我认为我们实际上在谈论的是，比方说，分辨率提高一千倍。我们已经能够回答一些非常基础的问题，实际上，关于大脑如何工作，使用这类表面记录方式，这是头皮表面电极无法做到的。而一旦进一步深入到单个神经元，你就获得了另一种分辨率，大约是六千到五千倍。

Is it one, ten, a 100? What's the scale at which you're thinking of that resolution? Well, would say from the scalp, let's say we just arbitrarily call that one, and then you think about what you could do with the CECOG, I think we're really talking about, let's say, a thousand times better resolution. We've been able to answer very fundamental questions, actually, about how the brain works using those kind of surface recordings in a way that's impossible with surface scalp electrodes. And then once you go take that further to single neurons, then you've got another resolution, probably 6,000 to 5,000.

最大的跨越就是从脑电图（EEG）到皮层脑电图（ECOG）。直接接触大脑。这是一个数量级的三次方变化。没错。而深入大脑内部则是五倍的变化。

The big jump is just going from an EEG to an ECOG. Directly to the brain. That's a three log change. Right. Whereas you're a 5x change going deeper.

其中一个原因是颅骨和头皮会导致信号大量损失。信号本身就很微弱，所以一旦你试图通过颅骨或头皮解读它们，它们基本上就消失了，而且非常分散。因此，几乎不可能精确地理解它们来自哪里。当你直接在表面记录时，你基本上就在信号源本身。细胞水平的信号记录，对于理解超精细分辨率非常出色，主要在我们使用它们的情况下，主要用于理解那些单元发生了什么。

And so one of the reasons for that is the skull and the scalp are a major loss of signal. The signals are small to begin with, so once you're trying to interpret them through the skull or scalp, they're basically gone, and very diffuse too. So trying to understand where they came from in any precise way is almost impossible. When you're recording directly on the surface, you're basically at the source itself. The cellular level, the signal cell recordings, are terrific for trying to understand that ultra fine resolution, primarily in the case that we use them for, for primarily to understand what's happening at those units.

但直到今天，仍然没有办法长期稳定地从相同的细胞记录。是因为免疫反应吗？也因为这是一个多么精细的问题，需要多么精确。我们谈论的是一个直径几微米的单个细胞，而你有一个电极。任何微小的运动，任何变化都会影响它。

But still to this day, there's really no way that you can chronically and stably record from the same cells. Because of the immune reaction? Also because of how fine of a problem it is, how precise it has to be. We're talking about a single cell, a couple of microns in diameter, and you've got electrode. Any micromotion at all, anything changes that.

因此，通常我们看到很多记录这些的系统，每天或每小时都有大量的更替。意思是你记录的神经元在漂移？正是如此。是的。这是否意味着，退一步说，你提到我们大脑中有820亿个神经元。

And so typically what we see with a lot of those systems that record from those is there's a lot of turnover from day to day or hour to hour. Meaning you're drifting between which neuron you're recording in? That's exactly. Yes. Does that imply then that I mean, just taking a step back, you said 82,000,000,000 neurons in our brain.

所以你把探针插入一个，它移动到下一个，再下一个，再下一个。像我这样的人可能会天真地认为它们都一样。就像上西区基本上完全相同的三排联排别墅。我们这里不是在谈论Tribeca。探针在这三个之间移动真的重要吗？

So you put the probe into one and it moves over to the next one and the next one and the next one. One, like me, would naively assume they're all the same. Those are like three row homes that are basically all identical on the Upper West Side. We're not talking about Tribeca here. Does it really matter if the probe moves between those three?

听起来答案是肯定的，但我好奇为什么。答案是肯定的。因为我们现在知道，紧挨着的细胞可能携带非常不同的信息。话虽如此，当你穿过皮层的一个柱状结构时，柱状是这种垂直组织，通常我们看的是表面的二维结构。但还有信息处理的第三维度，即皮层的不同层，我们称之为层状结构。

Sounds like the answer is yes, but I'm curious as to why. The answer is yes. Because we now know that cells that are right next to each other can have some very different information. Now that being said, when you go through a column of the cortex, the column is this vertical organization, typically what we're thinking about when we look at is the two dimension of the surface. But there's a third dimension of information processing, which is the different layers of the cortex we call the lamina.

通常，在一些感觉区域，例如，如果你放置一个电极，它主要会调谐到相同的信息，跨越这些不同的神经元，跨越那个深度。所以你是对的。在某些区域，你可能会有调谐到完全相同事物的神经元。对于解码目的来说，它随时间变化不大可能实际上不是什么大问题。在其他情况下，当你试图从混合程度更高的区域进行编码时，它可能会产生非常深远的影响，你必须每隔几小时或几天重新校准机器解释信号的算法。

And typically, in some of the sensory areas, for example, if you put an electrode, it's primarily going be tuned to the same information across those different neurons, across that depth. So you're right. In certain areas, you may have neurons that are tuned to the exact identical thing. And for decoding purposes, that may actually not be a big deal to have it not very stationary over time. In other instances where you're trying to code from areas where it's a lot more intermixed, it could have really profound implications where you have to recalibrate the algorithms that the machine is doing to interpret the signals every couple of hours or days.

那么当你进行ECOG时，你如何将传感器对准你想要到达的大脑部分？因为我假设它必须比简单地贴在皮层上要精细得多。是的。我们肯定是在深入细节，彼得，我喜欢你这一点。你不害怕深入细节。

So when you do ECOG, how do you direct the sensor at the part of the brain you wanna go to? Because I assume it has to be far more nuanced than just where you slap it on the cortex. Yeah. We're definitely getting into details, and I love that, Peter, about you. You're not afraid of getting into the details.

这暗示了我们之前讨论过的一件事。我大脑中负责说话的部分和你大脑中负责说话的部分，特别是在运动控制部分，大体上是相同的。它在同一个范围内。当我们深入到细节，微观地理时，有很多变化。但大体上在同一个城市，如果我们用地理来比喻的话。

This alludes to one of the things we were talking about earlier. The part of my brain and the part of your brain that is responsible for speaking, especially in the motor control part, is largely the same. It's in the same ballpark. There's a lot of variation when we come down to the details, the micro geography. But it's in the same, largely in the same city, if we're talking about geography.

你的房子和我的房子等等，在那个范围内会有点不同。使用ECOG或皮层电图的一个好特点是，你可以安全地将一个阵列覆盖在整个区域上，并且可以说，你可以非常密集地在整个城市进行采样。所以实际上，到最后，如果一个人在这里而另一个人在那里，并不重要。基本上，你都会覆盖到。这似乎实际上是一个特性，而不是一个缺陷，对吧？

Where your house is versus my house, etcetera, that's going to be a little bit varied within that. One of the nice features about using ECoG or electrocorticography is that you can put an array over that entire area safely, and you can sample very, very densely across the entire city, let's say. And so it doesn't really matter, actually, the end of the day, if one person's there and the others. Basically, you're going to cover it. That seems to actually be a feature, not a bug, right?

我的意思是，缺陷是你放弃了观察那栋房子厨房里发生的事情的分辨率，但你现在可以观察所有的房子。没错。而且你可以以一种非常安全和可扩展的方式做到这一点。我的意思是，你放弃的最大东西大约是80%的分辨率。是的。

I mean, the bug is you give up the resolution at what's happening in the kitchen of that house, but you now get to look at all the houses. Exactly. And you get to do it in a way that's very safe and scalable. I mean, the biggest thing you give up is 80% of the resolution, roughly. Yeah.

那么用ECOG，告诉我你从一名ALS患者那里每分钟可以捕捉多少个词。我们在UCSF的临床试验中做的是这是2023年的论文吗？是的。好的。这是《自然》杂志的论文。

So with ECOG, tell me how many words per minute you could capture from a patient with ALS. What we did in our clinical trial at UCSF Was this the 2023 paper? Yes. Okay. This is the Nature paper.

没错。我们在2023年发表了一篇论文。我们与一位名叫安的参与者合作。她大约二十年前患有非常严重的脑干中风。安多大年纪了？

That's right. We published a paper in 2023. We worked with a participant named Ann. She had a very severe brainstem stroke about twenty years ago. How old was Anne?

她当时二十多岁。结婚没多久，就在第二个女儿出生几个月后。她和朋友们打排球时突然倒下，被送往医院。她挺过了这次损伤。是椎动脉的问题吗？

She was in her 20s. It wasn't long after she had gotten married, just a couple months after her second daughter was born. She was playing volleyball with her friends, collapsed, taken to the hospital. She survived the injury. Was it a vertebral arteries?

是的。那是动脉夹层。没错。你医学院的记忆力其实相当不错。这很令人印象深刻。

Yes. That's a dissection. Yeah. This is Your just such memory from medical school is actually pretty good. This is impressive.

但回到安妮的情况，绝对是毁灭性的。为了让大家都明白，椎动脉——每个人都听说过颈动脉。好吧，颈动脉从我们的颈部向上延伸，主要为大脑前部供血。椎动脉则是一组同样重要、甚至更重要的动脉，它们供应脑干（连接大脑和脊髓）以及大脑后部。所以我们有两对非常重要的血管供应大脑，颈动脉和椎动脉。

But back to Anne, absolutely devastating. Just so people understand, vertebral artery, everyone's heard of the carotid arteries. Okay, the carotid arteries come up through our neck, and they primarily give the blood flow to the front part of the brain. The vertebral artery is an equally, if not more important, set of arteries that supply the brainstem, which connects the brain to the spinal cord, and the back of the brain. So we have these two pairs of really important blood vessels that come to our brain, the carotid and then the vertebral arteries.

而安妮在运动时受了伤。这真的很不幸，但她的椎动脉发生了中风，阻断了脑干的血液供应。所以从功能上讲，这意味着……我能问一个天真的问题吗？损伤必须是双侧的吗？如果只发生在一侧，另一侧不能通过Willis环代偿供血吗？为什么这种损伤会发生？

And Ann had an injury while she was playing. And it was really just unfortunate, but she had this stroke in the vertebral artery that blocked the blood supply to the brainstem. So functionally, what this means Can I ask a naive question? Does it have to be bilateral to cause the injury, or if it happens on one side, can the other side not perfuse around the circle of Willis? Why does that injury happen?

为了更精确地说明这一点，与颈动脉不同，椎动脉有左右两支。它们从颈部向上延伸，穿过颅底，通过枕骨大孔（基本上是脊髓穿过颅底的位置）。当它们进入颅腔后，会合并成一条动脉，称为基底动脉。基底动脉及其发出的穿支小动脉供应脑干，绝对至关重要。

Just to be even more precise about this, unlike the carotid artery, the vertebral arteries, you have a left and right vertebral artery. They come up through your neck and then they go through the base of the skull, through the foramen magnum, essentially where the spinal cord is coming through the base of the skull. When they enter the skull, they become one artery. It's called the basilar artery. And the basilar artery and the small perforating arteries that come off that supply the brainstem are absolutely critical.

所以这取决于夹层发生的位置。如果发生在分叉之前，你可能没事。如果发生在分叉之上或它们汇合的地方——不是分叉，但没错。是的，实际上你说得对。

So it depends where the dissection occurs. If it occurs before the bifurcation, you're probably fine. It occurs above the bifurcation or where they join, it's not the bifurcation, but yes. Yeah. So actually you're right.

有很多病例。事实上，有时我们出于各种原因，确实需要闭塞一侧椎动脉。然后另一侧可以通过侧支循环提供代偿血流。但基底动脉没有那种……是的，任务关键型。没有那种保险政策。

There are many cases. In fact, sometimes we, for various reasons, actually have to occlude a vertebral artery. And then the other one, just collateral, gives the collateral flow. The Basler, however, doesn't have that kind of Yeah, mission critical. Doesn't have that insurance policy.

没有备用系统。这是一个如此关键的结构。当那里出现问题时，通常实际上是终局性的。安妮在这次中风后幸存下来。她留下了四肢瘫痪，意味着她无法移动手臂和腿。

No backup. It's such a critical structure. And when there's a problem there, it's usually actually like terminal. Anne survived this stroke. She was left quadriplegic, meaning she couldn't move her arms and legs.

但除此之外，她无法说话，因为从大脑穿过脑干并通向颅神经（这些神经供应声道）的神经也直接受到了影响。然而，再次请原谅我的极度无知，那些应该是低位颅神经。没错。第三、第四、第五对神经（控制膈肌的）是完好的，所以她仍然可以自主呼吸。但第七、第八、第九对神经可能受损了，这就是她无法说话或类似功能受影响的原因吧？

But in addition to that, she couldn't speak because the nerves that come through the brain down through the brainstem and go to the cranial nerves, which supply the vocal tract, those were also directly affected. And yet, just again, you'll have to pardon my profound ignorance, those would be lower cranial nerves. That's right. Three, four, five, the ones for the diaphragm were intact, so she could still breathe on her own. But what is it, seven, eight, nine would have been compromised, which is why she couldn't speak or something in that neighborhood?

是的。所以特别是周围的颅神经，低位那些及其分布，它们控制舌头的运动。那是舌下神经，是第十二对。还有第十对，迷走神经。

Yeah. So it's the cranial nerves in particular around, the lower ones and those distributions that allow the control of the tongue. That's a hypoglossal nerve. That's number 12. It's number 10, the vagus.

但确切地说不是神经本身，实际上是脑干核团。神经起源的地方。完全正确。这不是任何类型的中风能预测到的。

But it's not precisely the nerves. It's actually the brainstem nuclei. Where the nerves originate. That's exactly right. And that's not something one predicts from any type of stroke.

这仅仅是脑干受影响部位的性质所致。完全正确。瘫痪是因为她的小脑也有梗死吗？不，不是。

It's simply the nature of what part of the brainstem was affected. That's exactly right. And was the paralysis a result of her cerebellum also having infarcts? No. No.

全都是与脑干相关的。只是脑干。确切地说，是我们称为脑桥的部分。毁灭性的。毁灭性的。

It was all brainstem related. Just brainstem. Good Precisely the part that we call the pons. Devastating. Devastating.

所以二十年来，安妮现在四十多岁，坐在轮椅上无法说话。没错。所以我认为重要的是，实际上是在她中风大约十八年后，她决定参加我们的试验。我们其实一年前就谈过。她说，我真的想等到我女儿毕业后再参加这个试验，然后我就可以和你们一起做了。

So this for twenty years, Anne is now in her 40s in a wheelchair unable to speak. Right. So I think some important things about this are that it was actually about eighteen years after her stroke that she decided to participate in our trial. And we had talked actually a year earlier. She said, I really want to wait to participate in this trial because I want to wait until my daughter graduates, and then I can do this with you guys.

我猜她这么说是因为发生灾难性事件的风险足够高，让她觉得需要等待。毕竟她是一位母亲。她想陪伴女儿，而且离毕业还有一年时间。她联系我们是因为我们之前有一位同样患有脑干中风的参与者，我们对她进行了治疗，进行了我即将描述的这项试验。她读到了相关报道，所以联系了我们。

And I assume she said that because the risk of something catastrophic happening was high enough that she felt she needed to wait. Well, she's a mom. She wanted to be there for her daughter, and she had a year before the graduation. And she reached out to us because we had an earlier participant, also with a brainstem stroke, that we treated, that we did this trial that I'm about to describe. She read about it, so she reached out to us.

当时她是如何沟通的？她主要的沟通方式是通过追踪眼球运动的设备。这些设备将眼球运动转化为指针，可以在屏幕上指向单个字母或单词。这是一种非常费力的沟通方式。我了解到安妮是个了不起的人，非常积极乐观的人。

How did she communicate at that point in time? So the main way that she communicates is through devices that can track her eye movements. Those are translated to a pointer that can point on a screen to individual letters or words. And so it's a very painstaking way of communicating. One thing I've learned about Anne is she's just a tremendous person, positive person.

她简直就是一股自然力量。她最近还用同样的系统撰写了一本书的章节。简直不可思议。好了，我们开始了这项名为BRAVO试验的研究。

She's just a force of nature. She recently actually used that same system to write a book chapter. Just incredible. Okay. So we started this trial called the BRAVO trial.

这是我们与FDA密切合作才获得批准的，因为它需要进行脑部手术。需要用到我们讨论过的这种经皮端口。我们能够以这种形式获得批准的原因是，我们使用的许多组件实际上是现有的医疗材料。因此在生物相容性和生物稳定性方面的安全性大体上是已知的。未知的是，如果有人十年或二十年没有说话，大脑的那些部分是否还能正常工作。

It was something that we worked with the FDA very closely to get approved because it requires a brain surgery. It requires this percutaneous port that we talked about. The reason we were able to get it approved in this form was that a lot of the components that we were using were actually existing medical materials. So the safety of it was largely already known in terms of its biocompatibility, its biostability. What was not known is that if someone has not spoken for a decade or two, whether or not those parts of the brain actually would still work.

是的。这很有趣，因为我们知道如果一个人失明多年，我猜枕叶的工作方式会不同。它不再处理信息，所以我不确定它是否真的会物理性萎缩，但我猜测神经元不会以同样的方式放电，对吧？没错。所以有趣的是，我们不知道安妮的内心独白是否仍在以同样的方式进行。

Yeah. It's really interesting because we know that if a person loses their sight for x number of years, I'm guessing that the occipital lobe doesn't work the same way. It's not processing the information, so it, I don't know that it actually physically atrophies, but I'm guessing that the neurons aren't firing the same way, right? That's right. So what would be interesting is we just don't know if Anne's inner monologue is still happening the same way.

对。这是个非常有趣的问题。我认为这实际上最终是最大的风险。虽然技术方面受到很多关注，但大脑运作的基本生物学原理以及信息是否仍在被处理，我认为实际上更为重要。因此我们进行了一次手术，植入了包含253个ECOG传感器的阵列。

Right. That's a very interesting question. And I think that ultimately that was the biggest risk, actually. There's a lot of emphasis on the technology, but the basic biology of how the brain works and whether that information is still being processed, I think, are really the more important ones, actually. And so what we did was we did a surgery where we implanted an array of two fifty three ECOG sensors.

这些是密集排列的传感器。多少个？253个。所以我们谈论的是大约信用卡表面积大小的东西，上面布满了间距约3毫米的电极传感器。每个传感器的直径约为1毫米。

These are the sensors that are densely spaced. How many? Two fifty three. So we're talking about something about the surface area of a credit card, and it's filled with electrode sensors that are spaced about three millimeters apart. Each sensor is about a millimeter in diameter.

所以基本上，我们在她大脑处理语言的部分——特别是控制嘴唇、下巴、喉部和舌头的单词运动产生区域——植入了一个信用卡大小的电极阵列。由于脑干中风，这些区域与她的声道功能上断开了连接，而脑干正是连接大脑与这些肌肉的桥梁。大约三周后，我们进行了手术，并开始了与她的研究会话。我们连接了电缆，基本上是一根HDMI线，它连接到一个头部基座上。这个头部基座负责转换来自她大脑的模拟信号。

And so basically, you've got this credit card sized array that was placed on the part of her brain that processes words, in particular the motor production of the words, the parts that control the lips, the jaw, the larynx, the tongue, areas that were functionally disconnected from her vocal tract because of this stroke in the brainstem, which connects the brain to those muscles. We did the surgery about three weeks later. We started our research sessions with her. We connected the cable, it's basically an HDMI cable, that is attached to a head stage. The head stage transforms the analog signals from her brain.

这些是微小的电压记录。我知道我可能讲得有点太深入细节了，但我觉得在信号处理方面这挺有趣的。你能解释一下为什么大脑是模拟的，以及为什么需要将其转换为数字信号吗？嗯，在某种程度上，它确实有数字化的层面。比如，当我们谈论动作电位时，它们是数字式的。

These are a small voltage recordings. I know I'd get into the weeds a bit much, but I think it's kind of interesting in signal processing. Can you explain why the brain is analog and why you have to convert that to digital? Well, to some degree, there is a level that it is digital. Like, when we talk about Action potentials are digital.

单个神经元、动作电位，就像是‘是’或‘否’的放电，类似于数字形式。但当我们记录大量这样的信号时，尤其是在ECoG（皮层电图）中，它是模拟的。它观察的是来自一群神经元——比如说几千个激活的神经元——的平均活动。我们过去十五年的工作实际上正是基于此，通过使用ECoG等方法，我们从中了解到存在一个映射，就像我们一开始提到的‘小人图’，但是一个迷你版的，对应着声道的那些部分：喉部、舌头、下巴。大约十年前，我们基本上弄清楚了这些信号如何对应英语中的每一个辅音和元音。

Single neurons, action potentials, like firing yes or no, like a digital form. But when we're recording a lot of these, especially at the ECOG, it's an analog. It's looking at the average of these from a population of, let's say, a couple thousand of those neurons activating. And the work that we've done actually over the last decade and a half, which led up to this, using methods like ECOG, we've learned from that there's a map, what we alluded to in the very beginning, like the homunculus, but a mini homunculus that is corresponding to those parts of the vocal tract the larynx, the tongue, the jaw. We figured out, essentially, how those signals correspond to every consonant and vowel in English about a decade ago.

这实际上是启动这项临床试验的动力，因为我们基本上已经识别出神经代码是什么样的，大脑的哪一部分，以及神经活动如何对应所有产生音节的运动，例如。创建这些知识需要多大的数据集？可能大约36位参与者的数据才能初步了解这个‘图板’。而如果那是36,000位，效果会好多少呢？

That was the impetus for actually starting this clinical trial, was that we essentially had identified what the neural code was like, what part of the brain, and how that neural activity corresponds to all the movements that create syllables, for example. How big a dataset was required to create that knowledge? Probably about 36 That's incredible. Participants' data to just get the basic idea of the board. And is this something where if that were 36,000, it would be how much better?

希望是完美的，近乎完美。我们会达到那个水平，因为事情正朝那个方向发展。好的。这如何扩展？我们如何利用其他个体的信息来帮助单个案例，比如说？

Hopefully perfect, like near perfect. We'll get to that because that's where things are going. Okay. How does this scale? How do we use the information from other individuals to help N of one, for example?

但在安特的特定案例中，我们从零开始。实际上我们没有使用那些数据。我们知道那是可能的。我们知道那些数据和代码的性质会是什么样子。与此同时，在我们进行所有这些研究的时候，彼得，人工智能也在并行发展。

But in Ant's particular case, we started from the beginning. We actually didn't use that data. We knew that it was possible. We knew what the nature of that data and that code would look like. And then at the same time that we're doing all of this research, Peter, AI is developing in parallel.

是的。所有我们现在每天都在使用的工具，比如将我们的声音实时转录成文本，我们使用了那项技术。我们实际上可以使用那些相同的技术来生成声音，称为语音合成。我们使用了现代人工智能中的许多相同工具——机器学习工具。我们现在将它们应用于大脑活动，并尝试用它们来翻译，例如，不是文本和合成语音之间的转换，而是从脑活动到语音。

Yeah. All of these tools that we now are using every day, transcribing our voice right now into text, we use that technology. We can actually use those same technologies that generate voices, called speech synthesis. We've used a lot of the same tools, machine learning tools, that are in modern day AIs. We're now applying them on the brain activity and trying to use them to not translate, for example, text and synthesized speech.

但现在情况不同了。它是将大脑活动转化为合成语音。输入的不是文本。输入的是这53个传感器上的ECoG活动。这当然是合乎逻辑的延伸。

But now the equation is different. It's translating it from brain activity to synthesized speech. The input is not text. The input is the ECOG activity across these two fifty three sensors. Which of course is the logical extension.

如果忽略计算成本，这样做是否有优势，因为你省去了一个中间步骤？是的。这是因为我们知道大致范围在那里，但我们知道每个人的大脑，在那个细节层面上，如果你要重建他们的话语，你不能只停留在大概范围。你必须基本上知道，就像，那个球场上的每一片草叶在做什么，而这在个体之间差异很大。所以我在想人工智能，机器需要做什么。

If you ignore the cost of compute, is there an advantage to doing it that way because you take out an intermediary step? Yes. It's because we know that the ballpark is there, but we know that everyone's brain, at that detail level, if you're gonna reconstruct their words, you can't just be in the ballpark. You have to know basically, like, what each leaf of grass on that ballpark is doing, and that's highly variable across individuals. So what is AI I'm just trying to think about what the machine has to do.

它的训练集是什么？我来给你解释一下。我们训练算法的方式，我们开始这个项目的方式是，我们在屏幕上给安妮提示和文本，基本上我们会请她尝试说出来。她能动嘴唇吗？她能稍微动一点，但不能说话。

What is its training set? I'll walk you through. So the way that we train the algorithm, the way that we started this was we would give Anne prompts on a screen and text, and basically we would ask her to try to say it. Can she move her lips? She can move a little bit, she can't speak.

所以她能移动下巴、嘴唇，但都无法清晰表达。她有我们所说的构音障碍。基本上，她能发出一点声音，但没有任何形式是可理解的。我明白了。但如果她的内心独白，如果你出示‘奶牛跳过了栅栏’这个词，她在心里说，信号是‘奶牛跳过了栅栏’，那我就完全明白它是如何工作的了。

So she can move her jaw, her lips, but none of it is intelligible. She has what we call anarthria. Basically, she can vocalize a little bit, but none of it is intelligible in any form. I see. But if her inner monologue, if you put up the word the cow jumped over the fence and she says, and in her mind, the signal is the cow jumped over the fence, then I totally see how it works.

是的。到那时，你就有无限的训练数据了。你基本上可以让她读《战争与和平》。对。让我澄清一下。

Yeah. At that point, you have infinite training data. You would basically just have her read war and peace. Right. So let me just clarify.

我们解码的区域不是处理内心独白或阅读的大脑部分。它确实是关于这种意志意图的部分。这真是个好说法。对吧？所以它不是关于她的阅读。

The area that we are decoding from is not the part of the brain that is processing either inner monologue or reading. It really is this part that is about this volitional intent. That's such a good To speak. Right? So it's not about her It's not reading.

感知。它不是阅读。所以当我在读‘奶牛跳过了栅栏’时。如果我仅仅想，我大脑的哪部分在内部化‘奶牛跳过了栅栏’？嗯，是你的视觉皮层。

Perception. It's not the reading. So when I'm reading, the cow jumped over the fence. If I just go, what part of my brain is internalizing the cow jumped over the fence? Well, your visual cortex.

是的。随着它进一步深入，它会进入一些语言区域。但它不一定激活瘫痪的嘴唇、下巴和喉部区域。因此，我们正在利用大脑中一个非常重要的部分。所以这是一项艰苦的练习。这需要她付出很多努力。

Yep. And then as it goes further, it's going into some of the language areas. But it's not necessarily activating the lips, jaw and the larynx, the areas that are paralyzed. And so we're tapping into a part of the brain that is really So this is a hard exercise. This takes a lot of effort on her part.

很多。让我描述一下那到底是什么。连续几天，我们会把一句话显示在屏幕上，并给她开始和结束的时间。在此期间，她只需看着这句话。她会给出一个开始提示，然后尝试说出来。

A lot. So let me describe actually what that was. So for days, what we would do is have a sentence on a screen, and we'd give her the start time and the end time. And during that, she would just look at the sentence. She'd give it a go cue, and then try to say it.

没有发出任何可理解的声音。她可能动了嘴唇也可能没动，但只是尝试说出来。结果证明这非常重要。天哪。就像，不能只是想着它。

Nothing intelligible comes out. She may or may not be moving the lips job, but just try to say. And that turns out to be very important. Oh my god. Like, can't just think about it.

不能只是读它。哇。你必须真正尝试说出来。而她就是这么做的。所以我们从一个非常简单的词汇表开始，大约有27个单词。

Can't just read it. Wow. You have to actually try to say it. And that's what she did. So we started with a very simple vocabulary of about 27 words.

我们选择的单词是北约代码词，阿尔法、布拉沃、查理、德尔塔、回声。我们这样做是因为我们可以测量，基本上，分析这些大脑信号并将其翻译成那26个不同代码词的解码器的准确性。在第一天，我们能够用大约一个半小时的数据集训练算法，达到大约50%的准确率。50%的准确率是指她能对一半，还是每次你给她看一个词时有50%的概率正确？两者都是。

The words that we chose are the NATO code words, alpha, bravo, Charlie, delta, echo. We did that because we could measure, basically, the accuracy of the decoder that was analyzing those brain signals and translating them into those 26 different code words. And on the first day, we were able to train the algorithm on a dataset of maybe about an hour and a half to get to about 50% accuracy. Does 50% accuracy mean she could get half of them right or any time you showed her one there was a 50% chance it would be correct? Both.

你刚才说的，在我们的意义上，是相同的。好的。但并没有偏向于她总是能正确识别其中一部分，而其他部分总是错误。实际上是有偏向的。是的。实际上，如果我深入细节的话，是的。

What you just said is, in our sense, identical. Okay. But there wasn't a bias towards a subset of them that she was always getting right and others that she was always There getting actually was a bias. Yeah. Actually, if I get into details, yes.

其中一些比其他更容易区分。这是基于音节数量吗？是的。实际上，这是基于音节数量以及一些语音特性。但对我们来说，北约代码词是一个非常有用的训练任务的原因之一是，北约代码词最初就是由军方开发的，目的是提高通信准确性。

Some of them were more discriminable than others. And was it based on the number of syllables? Yes. Actually, it was based on that and some of the phonetic properties. But one of the reasons why NATO code words for us was a really useful training task for us is because NATO code words were developed in the first place by the military to improve communication accuracy.

我们之所以实际使用这些代码词，是因为有时如果你只说A、B、D、Z，会产生很多混淆。这就是为什么我们实际使用这些代码词。它提高了区分度和可懂度，在很多场景下，你根本不会犯那些错误。例如飞行员和呼号。所以我们使用它是因为它具有很高的区分度。

The reason why we actually use those code words is because sometimes if you just say A, B, D, Z, there's a lot of confusion. So that's why we actually use those code words. It increases the discriminability and intelligibility, where a lot of those settings, you just can't make those errors. For example, pilots and the call numbers, for example. So we use that because it has high discriminability.

在第一天，我想我们达到了大约50%。这是直接转语音吗？这是转文本吗？这是直接转文本。好的。

And on that first day, I think we got about 50%. This is going straight to voice? This is going to text? This is straight to text. Okay.

是的。所以我们只是在尝试弄清楚，我们能否解码出是哪个词，并以文本形式显示？那是第一天，50%，对，第一天。然后在接下来的大约六天里，表现越来越好。大约一周后，她达到了95%到100%的范围。

Yeah. And so we're just trying to figure out, could we decode which word it was, and it was displayed in text? That's the first day, 50 That's first day, yeah. And then over the next, I would say about six days, the performance just got better and better. And then by about like a week into this, she was up into the 95%, 100% range.

所以这出乎意料。看到性能提升得如此之快真是不可思议。但那确实花了整整一周。现在问个问题。我确信北约代码不是为这个目的设计的。

So that was unexpected. It was incredible to see the performance increase so quickly. But that did take a full week. Ask a question now. And I'm sure that the NATO code is not designed for this purpose.

但大概，人们可以设计一系列词汇，这些词汇本身包含全部的音调、语音、音节组合，让你能用尽可能少的训练数据获得尽可能大的成果。这说得通吗？完全正确。人们该如何开发这样的东西呢？因为这是一个新问题。

But presumably, one could concoct a series of words that contain within them the full range of tones, of phonetics, of syllable juxtapositions that would allow you to use the smallest possible training data to get the largest possible outcome. Does that make sense? Absolutely. How would one even develop such a thing? Because this is a novel problem.

对。这实际上非常重要，而且可能比你意识到的更为深刻。你指的是语言的生成性。我所说的生成性是指，你可以利用这些本身毫无意义的单个元素，如辅音和元音，仅仅通过它们的不同组合就能产生所有可能的意义，就像DNA一样。DNA，我们有四个碱基对，本质上就是所有生命的密码。只不过DNA要简单得多，因为它是有限的。

Right. It's actually really important and more profound actually than you may realize. What you're referring to is the generative property of speech And and what I mean by generative is that you can take these individual elements like consonants and vowels, which by themselves have no meaning at all, and give rise to all possible meaning from just different combinations of them, just like DNA. DNA, we've got four base pairs, essentially as a code for all of life. Except DNA is so much easier because it's finite.

嗯。而且规则总是一样的。你可以定义所有规则。那里只有四个碱基对，它们只能以两种方式组合，并且每个都与它将变成什么有一对一的映射关系。而这里，你有26个字母。

Mhmm. And the rules are always the same. You can define all the rules. Here, you have there's only four base pairs and they can only combine in two ways and everyone has a one to one mapping with what it's gonna become. Here, you have 26 letters.

它们能以近乎无限的方式组合，然后还有所有这些愚蠢的例外。没错。这就是人工智能发挥作用的地方。让我稍微解释一下算法的工作原理，因为你问的问题实际上正是我们做这件事的核心所在。所以我们并不是直接从大脑活动转换到语音、单词和句子。

They can combine in a near infinite ways and then there are all these dumb exceptions. Right. So that's where the AI comes in. Let me just explain a little bit about how the algorithm works because what you asked about actually is very, very much at the heart of the way that we do this. So we don't go from the brain activity directly to speech and words and sentences.

最初在NATO项目中，我们就是这么做的。你可以使用一种叫做分类器的算法。它会查看活动模式，然后说，好吧，这个看起来主要像Beta。另一个主要像Echo。还有一个像Charlie。

In the very beginning with the NATO, that's what we do. You can use an algorithm called a classifier. It's gonna look at the pattern of activity and then just say, okay, it looks mostly like Beta. Another one looks mostly like Echo. Another one looks like Charlie.

好的。但要实现富有表现力的正常语音，你需要一种能够打开更多组合潜力以生成音节、单词、句子序列的东西。所以我们构建了一个解码器，它将大脑活动模式翻译成非常小的片段，十到二十毫秒的小块大脑数据，非常小的信号，信号的小窗口。机器学习会查看这些小窗口并做出有根据的猜测：大脑活动的映射如何与给定的辅音或元音相关联？

Okay. But to get to expressive, normal speech, you need something that actually can open up much more combinatorial potential to generate sequences of syllables, words, sentences. So what we did was we built a decoder that translates the brain activity patterns in very small segments, ten to twenty millisecond little chunks of brain data, really small signals, small windows of signals. And the machine learning is looking at those small windows and making an educated guess. How does the mapping of that brain activity relate to a given consonant or vowel?

现在我使用辅音元音只是因为容易理解。实际上我们使用了一种语音单位。像音素之类的？音素。是的。

Now I'm using consonant vowel just because it's easy to understand. The reality is we used a speech unit. Like a phoneme or something like that? A phoneme. Yeah.

但实际上是某种从语音识别算法中统计推导出来的东西。它是统计推导的，不是语言学上的或你在书里读到的东西。它实际上是一个计算单位，我们知道如果你能解码100个这样的单位，你就能生成流畅、可理解的语音。所以我们实际上使用人工智能来首先推导出这些单位是什么。

But actually something that was statistically derived from a speech recognition algorithm. It was statistically derived. It was not something that was linguistically or that you read about. It's really a computational unit that we know if you can decode 100 of these units, you can generate fluent, comprehensible speech. So we used AI actually to derive what those units would be in the first place.

我们采用了Meta大约五年前开源的一个语音识别系统。它是领先的语音识别算法之一。我们基本上提取了该神经网络中的神经元及其功能，然后尝试将它们映射到大脑活动模式。这是最前端的部分。解码的第一步是将神经活动模式翻译成这些仅十到二十毫秒长的单个语音单位。

We took a speech recognition system that Meta had made open source about five years ago. It's one of the leading speech recognition algorithms. We took essentially the neurons and what they do in that neural network, and then we try to map those actually to the brain activity patterns. That's on the very front end. The first step of the decoding is translating the neural activity patterns to these individual speech units that are just ten to twenty milliseconds long.

然后，它当然知道这些单位随时间变化的序列，因为这是算法计算的一部分。我们使用了一种叫做语言模型的东西，这是我们所有人现在在发短信时都熟悉的东西。它会自动纠正你的语音。为什么？因为它里面有一个英语模型，它知道特定序列应该是什么样子。

And then it, of course, knows the sequence of these units over time because it's part of the algorithm calculation. And we use something called a language model, which is something that all of us are now familiar with when you're texting. It autocorrects your speech. Why? Because it has got a model of English in there and that it knows what the particular sequence of the things should be like.

因此，即使很多数据有些模糊，但随着数据不断积累，你会得到一个序列，然后它基本上可以随时间做出最佳猜测，也就是我们所说的概率推断，判断在任何给定时间点最可能的单词或音素。最终我们可以构建句子。你从安妮那里感受到她的疲劳程度是如何进展的吗？换句话说，瓶颈是什么？随着她练习得越多，她完成这个说话动作是否会变得越来越容易？

And so even if a lot of the data is kind of fuzzy, as more data accumulates, you get a sequence, and then it can basically use a best guess over time, what we call probabilistic inference of what was the most likely word or phoneme at any given time point. And ultimately we could construct sentences. Did you get a sense from Anne as to how her level of fatigue with this progressed? In other words, what becomes the bottleneck? Does it get easier and easier for her to go through this talking motion as she practices more?

这是否就像我们认为的任何其他肌肉一样，有些萎缩了，而现在她正在恢复说话的能力？确实有点像。我们正努力让这个过程随时间变得更容易。我认为在最初的日子里，我们尝试了各种方法让它工作。其中很多，再次强调，都与这种说话的意志意图有关。

Is it just like any other muscle that we think of that has sort of atrophied and now she's sort of getting her talking back in shape? It is a bit of that. We're trying to make that easier over time. I think in the beginning days, we're trying everything to get it to work. And a lot of it, again, has to do with this volitional intent to speak.

事实证明这是最关键的事情。另一件我认为非常有趣的事情是，我们通过这些任务进行了大量的解码，随着时间的推移，实际上几个月后，它向我们报告了她的口面部肌肉、下巴和舌头的力量。通过这种持续的治疗和康复，它们实际上变得更强壮了。所以我认为现在的一切都是关于将大脑活动解码为人工数字事物。但我确实认为，在未来，脑机接口也将成为我们进行康复的一种方式。

That turns out to be the most critical thing. One of the things that I thought was really interesting also was we were doing so much decoding through these tasks that over time, actually a couple months into this, and it reported to us actually the strength of her orofacial muscles, her jaw, the tongue. They were actually getting stronger through this constant therapy, constant rehabilitation. And so I think right now everything is about just decoding the brain activity to an artificial digital thing. But I do think that in the future, BCIs are also going to be a way that we can do rehabilitation.

这是一种直接读取大脑试图做什么的方式。你可以 essentially 构建一个帮助人们说话的假体，但在这个过程中，一段时间没有说话的人会随时间恢复一些自然的力量。所以这是我们未来考虑的一个新适应症。如何利用这项技术来增强和加速康复？如果安妮今天中风，如果你与一个没有二十年或十八年不说话的人合作，这个过程会有多大不同，如果有的话？

It's a way that we have this direct readout of what the brain is trying to do. You can essentially build a prosthetic that helps people speak, but in the process, someone who hasn't spoken for a while will regain some of that natural strength over time. So that's a new indication that we're thinking about in the future. How to use this technology actually to augment and accelerate rehabilitation? If Anne had that stroke today, how different, if at all, would this process look if you were working with a person who hadn't spent twenty years or eighteen years without speaking?

毫无疑问，我认为它会工作得更快。需要学习的东西更少。对她来说，十八年不说话基本上意味着她必须重新学习如何说话，而我们必须跟上她的重新学习。她的大脑可能正在重组，重新学习一些那些基本的东西。她可以看到反馈， essentially 判断她试图说的是对还是错。

There's no question that I think it would work faster. There's less to learn. For her, not speaking for eighteen years basically meant that she basically had to relearn how to speak, and we had to keep up with her relearning. Her brain was probably reorganizing, relearning actually some of those fundamental things. And she could see the feedback of essentially whether or not what she was trying to say was right or wrong.

这是一项非常紧张的工作，所以我们正努力让这个过程随时间变得更容易。但我认为当然，这些活动、那些记忆、我们之前讨论的突触保存得越好、越近期，它们就越稳定、功能越强，解码它们就越容易。那么当前技术的上限会是什么？你认为当前技术（因为在她的情况下是ECOG，对吗？对）每分钟能处理多少单词，分辨率和准确性如何？

And it was very intense work, so we're trying to make that easier over time. But I think certainly the more preserved, the more recent that activity is, those memories, the synapses we talked about earlier, the more stable, the more functional they are, the easier it is to actually decode them. So what will be the ceiling for the current technology? How many words per minute and at what resolution or accuracy do you think the current technology because this was ECOG in her case, correct? Right.

你认为它会走向何方？这个渐近线会在哪里？我们在这个领域看到了很多进展。同时或不久之后，我们正在做的事情，有其他团队基本上也能看到类似的效果。我们的主要来自大脑表面。

Where do you think it's going to go? Where will this asymptote? We're seeing a lot of progress in this field. At the same time, or soon after, what we were doing, there were other groups that basically could see similar effects. Ours was primarily from the brain surface.

其他研究小组，我的亲密同事们，现在能够使用这些皮层内阵列通过植入大脑内部的电极来实现这一点。所以看起来不同的方法都是可行的。我认为关键问题在于未来对许多患者来说，什么才是正确的形式。与安妮一起，我们平均能达到每分钟约80个单词，有时甚至更快。比较一下，你我舒适地说话能说多少词？

Other groups, close colleagues of mine, were able to now do this with electrodes that were inside the brain using these intracortical arrays. So it seems that it's possible with different approaches. I think what is going to be a key question is what's going to be the right form moving in the future for many patients. With Anne, we were able to get about 80 words per minute on average, So sometimes much faster than that. Comparison, how many words can you and I speak comfortably?

你我现在的语速可能大约在每分钟150到160个词。哇。所以她的说话速度能达到你的一半。这相当了不起。是的。

You and I are probably doing about a 150, a 160 words per minute right now. Wow. So she could speak at half the rate you could speak at. That's pretty amazing. Yeah.

而且并不是说语音输出超级慢。只是存在这种内置的延迟时间，我们用它来将大脑活动转化为那些单词和句子。我们在23年发表的论文中...你们在最近的论文中延迟时间非常短，对吧？完全正确。在23年的论文中，我们的解码策略是获取这一系列解码出的语音元素序列，然后我们可以查看该序列并应用语言模型中的解码算法来重建完整句子。

And it's not like the speech was coming out super slow. It's just that there's this built in latency time that we use to translate the brain activity into those words and sentences. And what we published in '23 You had a very short latency in your more recent paper, didn't you? That's exactly right. In the '23 paper, our decoding strategy was to take this sequence of decoded phonetic elements, and we could look at that sequence and then apply the decoding algorithm in the language model to reconstruct full sentences.

事实上，我们甚至能合成它们，并且实际上个性化地恢复到她受伤前的声音。在我们今年刚发表的一项最新研究中，我们能够以流式方式实现这一点，每个语音元素之间的延迟不到一秒。所以我们不是在等待整个句子完成，而是在实时进行解码，既清晰又快速。你认为这能把语速提升到多少？基本上，能快到她想说多快就多快。

And then we could even synthesize them, in fact, and personalize them actually to her pre injury voice. In a more recent study that we just published this year, we were able to do this in a streaming way with less than a second latency between each phonetic element. So it's not like we're waiting for the whole sentence to occur, but we're doing decoding on the fly, and it's intelligible and fast. And that will get the words up to what, you think? As quickly as she can try to say them, basically.

这些都是用相同的硬件吗？是用相同的硬件。完全不同的算法。在颅内硬件方面，显然材料科学正在大力推动寻找尽可能免疫惰性的物质。这是你们在那方面的挑战。

And this is all with the same hardware? This is with the same hardware. Totally different algorithm. On the intracranial hardware, obviously there's a big material science push to come up with the most immunologically inert substance possible. That's your challenge there.

但对于ECoG（皮层电图），你们是否在等待另一个硬件阶跃变化？并不完全是。我的意思是，我认为最令人兴奋的是我们现在已经有了这项技术。我们需要以合适的外形尺寸进行优化。我想，只是要转向完全可植入的设备。

But with the ECOG, is there another hardware step function you're waiting for? Not really. I mean, I think the thing that's most exciting about this is that we have the technology now. We got to optimize it in the right form factor. I mean, I guess it's just moving to a fully implantable device.

那样就不必处理感染风险了。所以实际上我们需要拥有通道数多得多的阵列。上次我谈到信用卡大小带有253个通道。我们希望能有传感器数量四倍于此的设备。当你想到英伟达或台积电正在做的事情时，这似乎完全是可以实现的。

That's So you don't have to deal with the infection risk. So we need to have the array that will have a lot more channels, actually. So last time I talked about a credit card size with $2.53. We'd like to have something that has four x that amount of sensors. This seems completely achievable when you think about what NVIDIA is doing or TSMC.

我的意思是，这在我看来是非常容易解决的。确实如此，而且我们现在就在做这件事。对于任何医疗设备，你都需要把所有部件整合起来并加以改进。所以我们已经将这些具有极高带宽的组件无线连接到这个阵列上。我认为在很多方面，我们已经完成了困难的部分，比如安妮所做的，潘乔所做的。

I mean, that strikes me as very solvable. It is, and we are doing it right now. With any medical device, you've to put it all together and improve it. So we've taken these components that have very high bandwidth wireless connected to this array. And I think in many ways, we've done the hard part already, like what Anne did, what Pancho did.

他是我们早期的参与者之一。沃尔特正在做的事情。这些是不可思议的人，他们实际上是世界上第一批能够实现这一目标的人。真正的先驱者。那才是困难的部分。

He was one of our earlier participants. What Walter is doing. These are incredible people that were really the first people in the world, actually, to be able to achieve this. Real pioneers. That was the hard part.

困难的部分总是第一次。是的。当然。这是概念验证。这就是概念验证。

The hard part is always the first time. Yeah. For sure. It's the proof of concept. It's the proof of concept.

老实说，现在的一切实际上都只是优化问题。你现在是否更多地将其视为一个工程问题？是的。让我们现在扩展它。

Everything now is actually just about optimization, to be honest with you. Do you think of this more as an engineering problem now? It is. Yes. Let's now expand it.

所以你已经有了这个工程问题的概念验证，即大脑工作，运动系统不工作，我们可以提取语音。那我们一开始讨论的其他问题呢？比如肌萎缩侧索硬化症（ALS）呢？不是为了语音，而是为了呼吸功能。一个ALS患者，我假设——我其实不太了解或不确定——但我想他们最终会死于呼吸系统并发症，无论是误吸还是类似的问题。

So you have the proof of concept for the engineering problem that says brain works, motor system doesn't work, we can extract speech. What about these other problems that we talked about at the outset? What about ALS? Not for speech but for respiratory function. A patient with ALS is, I assume, I don't actually believe it or not know much about it, but I assume that they ultimately succumb to respiratory complications and whether it be aspirations or things like that.

所以如果我们能克服这个问题，绕过退化的运动神经元，基于我们今天看到的技术，是否存在针对ALS的工程解决方案？当我们说解决方案时，是指为某人保留沟通能力吗？嗯，我想说，让我们甚至超越说话的能力，而是例如正常呼吸的能力。最终是不丧失运动功能的能力。是的。所以要做到这一点，基本上还需要在工程上进行几个步骤的飞跃，你基本上是在谈论绕过神经系统中相当大的一部分。

So if we could overcome that problem and bypass the degenerative motor neurons, is there an engineering solution to ALS based on the type of technology we're seeing today? When we say solution, mean to preserve communication for someone? Well, I would say let's go even beyond the ability to talk, but the ability to breathe normally, for example. And ultimately the ability to not lose motor function outside of Yeah. The So to do that basically is another couple of step functions in engineering where you basically are talking about bypassing a pretty significant section of the nervous system.

所以你将接入大脑以获取一些控制信号。其中一些你甚至不需要接入大脑。对于呼吸，如你所知，很多是硬连线的。我们当然不会去想它。例如，脑干中的中枢模式发生器对于呼吸模式非常重要。

So you're gonna tap into the brain to get some of the control signals. Some of this you don't even need to tap in the brain. For breathing, a lot of it is, as you know, is wired. We're not thinking about it certainly. Central pattern generators in the brainstem, for example, are really important for that breathing pattern.

埃迪，这听起来可能有点天真，但为什么我们不能在颅骨外连接所有颅神经，创建一个完全自动化的呼吸系统呢？就像是为膈肌和胸壁设计一个类似心脏自动除颤器（AICD）的装置。我们几乎把所有时间都花在了讨论大脑方面。但你可以想象另一个全新的领域和努力，即构建电子设备，这些设备甚至不一定需要接入神经，比如颅神经或支配膈肌的颈神经，而是绕过这些神经，直接作用于肌肉。

This might sound naive, Eddie, but why is it that we couldn't wire into all of the cranial nerves outside of the cranium and create a respiratory system that is fully automated? Like almost think of an AICD for the diaphragm and chest wall. So we've spent almost all of our time really talking about the brain side. But then you can imagine another whole new enterprise and endeavor of building the electronics that not necessarily even tap into the nerves, the cranial nerves, let's say, or the cervical nerves that go to the diaphragm. But you bypass those too, and you go directly to the muscles.

是的，完全正确。所以有一个领域，我们虽然没有直接进行这项研究，但它与未来的发展方向高度相关，那就是功能性电刺激（FES）。它将脑机接口——解码大脑活动并转化为控制信号的设备——与通过植入肌肉的刺激电极实际作用于肌肉，实现协调运动相结合。

Yeah. Exactly. And so there is a field, we're not directly doing this research ourselves, but it's highly relating to where the future is. It's called FES, functional electrical stimulation. So coupling the brain computer interface, the device that's decoding the brain activity, translating into the control signals, and then actually acting on the muscles through stimulating electrodes that are in the muscles themselves and doing that coordinated movement.

呼吸实际上是一个很有趣的例子，因为它不像恢复手部功能那么复杂。有趣的是，如今每个人都认为，要想站在技术前沿，就必须专注于计算机科学。但事实是，在生物工程方面，你同样需要强大的技术支持——电气工程、生物医学工程、机械工程，甚至材料科学。

Breathing actually is a really interesting one because it's not as complex as restoring our hand. It's interesting. Everybody assumes today if you really want to be in the forefront of technology, you need to be on the CS side. But the truth of the matter is you'd need just as much horsepower on the bioengineering side here. Electrical engineering, biomedical engineering, mechanical engineering, I mean these are material science.

我的意思是，这类问题是所有高科技领域的交汇点，从人工智能到计算机科学，再到各个工程学科，并与医学相结合。而且你还必须有外科医生的参与。你说得完全正确。我认为你切中要害，因为在很多方面，真正的挑战其实不在于技术本身，而在于如何让工程师与神经外科医生、神经学家、神经科学家同处一室，以高度协同的方式共同思考如何解决这个问题。

I mean these are This type of problem is the intersection of everything that is high-tech from AI to computer science to all disciplines of engineering, coupled with medicine. And you have to have the surgeon too. That's exactly right. And I think that you hit the nail on the head because in many ways that's the challenge actually, more than the technology itself. It's really how do you get the engineer in the room with a neurosurgeon, with a neurologist, the neuroscientist, all thinking in a really concerted way about solving this problem?

未来你会看到的是，这将越来越演变成一个生物学问题，将生物学视为下一代技术解决方案，比如使用与大脑交互的工程细胞而非金属电极，通过生物学而非半导体进行计算的新方式。我认为，这最终是未来的发展方向。嗯，请详细说说。我的意思是，已经有一些人在讨论这个，但我希望人们能更深入地理解你的意思，因为这很复杂。确实很复杂。

And then what you're going to see in the future is that this is going to evolve more and more as a biological problem, thinking about biology as the next technology solution, engineered cells that are interfacing with the brain as opposed to metal electrodes, New ways of doing computing that are through biology, that are not through semiconductors. That, I think, ultimately is where things are going go in the future. Well, say more about that. I mean, this is There are some people that are already talking about this, but I'd like people to understand more what you mean by that because it's complicated. It is complicated.

我真正谈论的其实是接下来的几步。但这个问题被提出的原因之一，是你之前说得非常精确。好吧，假设你有一个电极系统，正在记录一个细胞的活动。

What I'm talking about really is, I think, the next couple of steps. But one of the reasons why this comes up is that you actually said it really precisely before. Okay. You've got this electrode system. Let's say you're recording from one cell.

最好的情况是，你打造了一个电子系统，也许能处理10个通道，未来可能达到40甚至1000个通道。但分母是860亿。我们不在同一个数量级上，规模完全不同。生物学一直都能做到这一点，它已经解决了许多这类规模化的问题。

Best case scenario, you beat an electronic system that can maybe do 10, maybe 40 in the future, 1,000 channels. But the denominator is 86,000,000,000. We're not in the scale, not in the same regime of scale. Biology has done that all along. Biology has solved a lot of these scaling problems.

具有相同基因编程的细胞会因为其环境和其他因素而增殖。它们会专门化以执行特定功能。我们的大脑就是这样。每个单独的细胞都有相同的基因程序，但由于其局部微环境，最终具有不同的身份和不同的目的。因此我认为这确实超越了电子工程的思维，真正进入了生物工程的领域。

Cells that have the same genetic programming multiply because of their environment, other factors. It becomes specialized for a specific function. That's how our brain is. Each individual cell has the same genetic program, but because of its local meliu ends up having a different identity, different purpose. And so I think that is really thinking outside of the electronical engineering, really moving into the realm of bioengineering.

这个领域发展相当迅速。有一个我们称之为类器官的完整领域。这是通过细胞培养或干细胞创建微型大脑，构建微型脑组织，目前主要用作疾病模型，但也作为测试新药物的方法。但我们将看到这些与脑机接口世界进行交互。所以我确信这肯定是未来的一部分。

And this field is moving pretty fast. There's a whole field that we call organoids. This is creating mini brains from cell cultures or stem cells, building miniature brains, primarily being used as models of disease right now, but also as ways to test new drugs. But we're going to see these now interfacing with the world of, brain computer interfaces. And so I think that that's part of the future for sure.

这非常令人兴奋。虽然不是近期就能实现，但未来技术确实与生物学密切相关。对于2030年2月，您对该领域的延伸目标是什么？延伸目标我定义为事情必须进展顺利，但我们不是在谈论科幻小说。到2030年2月，我希望这些系统能够真正面向更广泛的市场。

It's very exciting. It's not near term, But there certainly is something about the future of technologies actually in biology. What is your stretch goal for the field in 02/1930? So stretch goal meaning, I define that as things have to go well, but we're not talking science fiction. By 02/1930, I hope that we have these systems actually available to a much broader market.

就像我们在研究环境中、在非常受控的环境中已经证明这是可以做到的，这是概念验证。真正需要做的是大量的硬工程工作，使其变得实用、可用，对患有各种不同神经系统疾病的人有用，不仅仅是ALS，还包括脊髓损伤、中风、多发性硬化症，这是一个挑战。每个人可能有非常特定的需求。我们需要能够解决这个问题。这是一个优化过程。

Like, we have shown in a research setting, very controlled setting, that this can be done, the proof of concept. What really needs to be done is a lot of hard engineering to make this practical, usable, useful for people with a variety of different neurological conditions, not just ALS, but spinal cord injury, stroke, multiple sclerosis, and that's a challenge. Everyone may have a very specific need. We need to be able to solve that. It is an optimization.

这是可以解决的。这就是我希望到2030年2月能看到的情况。让我们完成其中几个项目，让它们真正走出实验室帮助人们。基于现有的专业知识，是否有当前的公司或一组公司是解决这个问题的天然所有者？或者您所说的是基本上需要获得资本并从头开始的新公司？

It can be solved. That's what I'd love to see by 02/1930. Let's get a couple of these across the finish line so that they're actually out in the world helping people. Is there a current company or set of companies that are the natural owner to solving this problem based on their existing expertise? Or is what you're talking about basically new companies that have to become capitalized and do this de novo?

谁会是这个领域的天然所有者？我认为两者都有。最著名的可能是Neuralink，埃隆·马斯克的公司，他们采用非常特殊的方法，通过机器人手术将电极植入并缝合到大脑中，试图以最高分辨率进行记录。我认为这方面取得了很大进展，但我们也看到了很多挑战。在这个规模上解决这个问题确实是一个艰难的技术难题。

Who would be the natural owner of this? I think it's both. So the most famous probably is Neuralink, Elon Musk's company that has a very specific approach where you have a robot that is surgically inserting and sewing electrodes into the brain and trying to record from that very finest resolution. And I think there's a lot of progress with that, but also we've seen a lot of challenges. It's a really hard technical problem to solve at that scale.

还有一系列其他公司也在从事类似的工作。我们正在研究的一种方法是高度定制化的ECoG方法，因为基本上我们已经从大量工作中知道它是有效的，我们可以使其分辨率比以往更高，并通过完全可植入的系统使其更加安全。随着时间的推移，我们将看到这会变得越来越微创。就像我们在对话一开始谈到的那样，手术随着时间的推移变得越来越微创。脑机接口也将变得越来越微创。

There's a variety of other companies in that vein. One of the things that we're working on is a highly customized ECOG approach, because basically we already know that it works from a lot of the work that we've done, and we can make it a lot higher resolution than we've done before, and make it much safer with a fully implantable system. And then we're going to see more and more over time that this is going to become less and less invasive. Just like we were talking at the very beginning of our conversation, surgeries have become less invasive over time. Brain computer interfaces will become less invasive.

我们正处于这个故事的起点。目前最重要的是通过高度侵入性的方法获取尽可能多的数据。但我认为随着时间的推移，我们会逐渐减少这种侵入性。事物总是这样演进的，使其更具普适性，让人们更容易、更安全地操作。那么，当你说到更少侵入性时，你认为将来是否有一天可以通过头皮表面的脑电图（EEG）来实现？

We're at the very beginning of this story. Getting the most amount of data right now is the most important with highly invasive approaches. But I think as time goes on, we're going to back out from that invasiveness. That's always how things evolve, to make it more generalizable, easier and safer for people to do. Now, when you say less invasive, do you think there will ever be a day when you can do this off an EEG on the surface?

还是你认为，不，它会更像是从微创手术到开放手术的过渡，比如不是开颅手术，而是在那里钻一个小孔，通过硬脑膜植入一个微小的芯片，然后完成？我认为是后者。颅骨外部的分辨率可能永远无法达到足够好的水平。这是一个我认为很多人试图解决的物理问题。电池永远无法像碳氢化合物那样高效地储存能量，这是肯定的。

Or do you think, no, it will be more like minimally invasive surgery to open surgery where instead of a craniotomy, we're going to bore a single hole in there, we're going to put a small tiny chip in through the dura, implant it on there and we're done? The latter. The resolution at the outside of the skull is probably never going to be good enough. We're talking about a physics problem I think a lot of people have tried to solve. Batteries will never store energy nearly as well as hydrocarbons, full stop.

理论上我们可以从头皮获得那种分辨率，但实际上，还没有人能够突破这一点。许多聪明人都研究过这个问题。是的，很有意思。我知道设备可以继续微型化，手术也可以继续变得更安全。

That level of resolution that we have from the scalp in theory, I think, but in practice, no one has been able to crack that. A lot of smart people have worked on that problem. Yeah, interesting. I do know that devices can continue to be miniaturized. I know that surgery can continue to be safer.

因此，在历史的某个时刻，这些设备将不再仅仅用于医疗应用，而是会达到增强功能的水平。当那一天到来时，我们将不得不面对巨大的伦理问题。目前我们还没有到达那个阶段，但我对这项技术充满信心。

So we will see this point in history where devices at some point are not going to just be about medical applications. They'll be essentially enhancement level. There's huge ethical questions that we're gonna have to deal with when that time comes. We're not there right now. But I would bet on the technology.

我们并不是说要违背任何物理规则和定律来实现这一目标，只是在讨论如何缩小电子设备的尺寸，使其变得更小。但随着时间的推移，一切都会变得不那么侵入性。我相信你经常被问到这个问题，但回到安妮的故事起源，许多人遭受脑损伤。如果你能挥动魔法棒，你可能会希望她大脑受损的部分能够再生。

We're not talking about breaking any rules and laws of physics in order to get there. We're just talking about scaling electronic or miniaturizing it in a way that is just a smaller form factor. But over time, everything becomes less invasive. So I'm sure you get asked this question all the time, but going back to the origin of Anne's story, so many people suffer brain injuries. If you could wave a magic wand, you would just hope for some regeneration of the injured portion of her brain.

我猜在安妮的情况下，受损细胞的总量其实很小，可能只有你拇指的一半大小，对吧？我的意思是，虽然相对较小，但它恰好位于她身体中最宝贵的区域。那么，对于未来干细胞干预在再生方面的潜力，特别是在中枢神经系统（CNS）中，我们是否有所了解，或者你有什么看法？是的，我认为这个领域大约在十到十五年前受到了很多关注。

And my guess is in the case of Anne, the actual total volume of cells that are damaged is quite small. It could be this half the size of your thumb, right? I mean, it's a relatively small, but it just happened to be in the most precious part of real estate in her entire body. So do we know or do you have any point of view on the potential future of stem cell like interventions for the purpose of regeneration, specifically in the CNS? Yeah, I mean, this is an area that I think got a lot of focus and attention maybe about ten or fifteen years ago.

我会说，很大程度上结果相当有限。是的，最多只能说是勉强。现在它又回来了，主要是因为许多基于细胞的疗法、类器官，以及在细胞培养中构建微型大脑模型。我认为我们将首先看到的，并且我看到一些希望的，是在大脑的小目标区域中非常精确地替换已丢失的细胞。

And I would say largely the results were pretty modest. Yeah, at best. Yeah, at best. It's coming back now because of a lot of cell based therapies, organoids, building miniature models of brains on cell cultures, basically. I think the first things that we're going to see, and where I am seeing some promise, is very focal delivery in replacing cells that have been lost in small targets of the brain.

那么回到帕金森病，你有多巴胺能神经元和黑质退化的问题，目标是你能否替换并基本上将一些干细胞移植到大脑的那个部位？提醒我为什么黑质中的细胞会死亡，我们知道是什么在杀死它们吗？可能是多方面的。很可能是遗传因素。有一些特定基因容易导致那里的退化。

So back to Parkinson's disease where you've got degeneration of dopaminergic neurons and the substantia nigra, the goal is can you replace and basically transplant some stem cells into that part of the brain? Remind me why the cells in the substantia nigra, do we know what's killing them? It could be multiple fold. It's probably genetic. There are certain genes that predispose to degeneration there.

有一些环境毒素可能导致退化，然后还有一大类我们仍然不知道原因的情况。但归根结底，这些高度特化的细胞确实发生了退化。大多数治疗都围绕多巴胺替代药物。你认为我们离移植治疗还有多远？

There are certain environmental toxins that can cause the degeneration, and then there's like a huge bucket. We still don't know what's causing that. But at the end of the day, there is a degeneration of those very specialized cells. Most of the treatments are around dopamine replacement medications. And how close do you think we are towards transplant?

实际上这已经在二十、三十年前就做过了。哦，真的吗？我知道使用胎儿移植物的方法。它们只是没有成功？有些确实成功了。

It's already been done, actually, like twenty, thirty years ago. Oh, really? Was aware of using fetal grafts. They just didn't take? Some of them took it.

事实上，一些患者从中获益。副作用也相当严重。什么样的副作用？如果多巴胺过多，你实际上可能出现运动障碍。也就是过度运动。

In fact, some patients got benefit from it. The side effects were also fairly severe. What kind of side effects? If you have too much dopamine, you can actually get dyskinesias. So hyper movement.

所以这是帕金森病的一个认知症状。运动减少。是的，特别是运动迟缓，你的动作变慢，启动动作也很缓慢。但如果细胞只是不断分泌多巴胺，它们也可能分泌过多，你就会得到相反的效果。

So one of the cognitive symptoms of Parkinson's. Hypomovement. Yeah. Bradykinesia specifically, where you have slowed movements, slow to initiate movements as well. But if you have cells that are just pumping out dopamine, they can also be putting out too much, you get the opposite effect.

所以这不仅仅是把它们放进去那么简单。它们实际上需要以正确的方式调节，以输出适当的水平。因此，我们正在UCSF非常感兴趣试验新一代的新疗法，这些疗法有更好的细胞模型，能更好地控制涉及的多巴胺。我们有更好的递送系统。你能想象吗？

So it's not as simple as just putting them in there. They actually have to be tuned in the right way to put out the right levels. So there's a new generation of new therapies that we're really interested in trialing at UCSF that are much better cell models, much better control the dopamine that's involved. We have much better delivery systems. Could you imagine that?

你能想象通过工程方法解决帕金森病吗？我们正在努力。那么合成细胞呢？你可以完全控制它。所以再次，你有基质问题，但如果它真的是合成细胞，那么它大概也能制造多巴胺，而不是某种可植入的缓慢释放多巴胺装置，然后你想出某种巧妙的方法来补充。但你认为哪种更可能？

Could you imagine engineering your way out of Parkinson's disease? We're working on it. What about synthetic cells where you completely get to control it? So again, you have the substrate problem, but if it's truly a synthetic cell, then presumably it can make dopamine as well as opposed to an implantable slow leak dopamine that you come up with some slick way to refill. But what do you think is more likely?

是采用更纯粹的工程方法，还是更偏向生物移植的方法，你只是试图调整它？近期当然是采用一些细胞培养，我认为这仍然是一个巨大的目标，不仅仅局限于大脑。比如，你能在没有原始细胞的情况下从头生成一个细胞吗？这需要免疫调节吗？哦，绝对需要。

The more pure engineering approach or the more biologic transplant approach where you just try to tune it? The near term, of course, is taking some cell cultures that That's are not purely still, I think, a huge goal outside of just brain. Like, can you generate a cell de novo without some origins? And does that require immune modulation? Oh, absolutely.

所以这是一个完整的移植？是的。所以很多这些患者最初会因此接受免疫抑制治疗。但这也已经改善了很多。免疫抑制的程度就像他们接受了肾移植、肝移植或心脏移植一样吗？

So it's a full transplant? Yeah. So a lot of these patients initially will be on immunosuppression for that. But that's also improved a lot. As immunosuppressive as if they had a kidney transplant or a liver or heart transplant?

是的。哇。是的。我认为目前主要是这个级别的预防措施。在努力使这些东西尽可能不具有免疫原性方面正在取得进展。

Yes. Wow. Yeah. I think that's primarily right now the level of precaution. There is progress being made in trying to make these things as least immunogenic as possible.

这正是很多工程努力的重点，就是使其尽可能不具有免疫原性，以避免排斥情况。所以我对这一点感到兴奋。这就是我之前谈到的一些生物工程，生物技术或技术的未来，真正回归生物学，稍微远离电气工程。所以在十五年后，到2040年2月，你仍然会在做手术。你可能正处于职业生涯的最后十年或十五年。

That's where a lot of the engineering actually is focused on, is just make it the least immunogenic to avoid a rejection scenario. So I am excited about that. And that's some of the biological engineering that I was talking about, biotechnology or the future of technology, really coming back to the biology, moving a little bit away from the electrical engineering. So in fifteen years, in 02/1940, you're still going to be operating. You'll probably be in the final decade or fifteen years of your career.

所以按外科医生的标准，还有很多工作要做。你认为2040年2月的世界会是什么样子？你认为今天摆在你面前的主要问题中哪些会得到解决，其影响会是什么？我认为事物变化的进程以及现在有多少事情正在被解锁，我们很接近了。我认为我们真的非常接近了。

So by a surgeon's standards, plenty of work to do. What do you think the world looks like in 02/1940? Which major problems that stand in front of you today do you expect to fall and what will be the implications? I think that the course that things are changing and how many things are being unlocked right now, we're close. Think we're really getting close.

其中一些方法并不标准，因为副作用太严重，但它们可能具有治疗效果。我们需要进行这种调整和优化。外面有很多概念验证，但就像我之前提到的，99%的工作在于优化，在于工程。我确实认为，既然我们现在理解了像胶质母细胞瘤这样毁灭性疾病的分子和遗传驱动因素，我们将拥有更强大的工具，有望使其成为一种慢性病，而不是平均18个月内的生死判决。话虽如此，通过手术，我们可以延长到几年，很多年。

Some of these things are not standard because of the side effect profiles are too severe, but they can have therapeutic efficacy. We need to do that tuning this optimization. There's a lot of proof of concept out there, but like I alluded to earlier before, 99% of the work is in the optimization, in that engineering. I do think that now that we understand what are the molecular and genetic drivers of a disease as devastating as glioblastoma, we will have way more powerful tools that will hopefully make it a chronic condition as opposed to a life death sentence in eighteen months on average. That being said, with surgeries, we can get out to years, many years.

但我们的目标是使其慢性化，甚至可能治愈，本质上是通过攻击其机制。我们现在知道了哪些基因发生了改变。我们需要能够启动免疫系统来识别——在这方面投入了大量努力试图弄清楚。我确实认为，并且我对神经退行性疾病非常乐观。有太多有希望的事情了。

But our goal would be to make it chronic, potentially cure, by essentially attacking the mechanisms. We now know the genes that are altered. We need to be able to turn on the immune system to recognize huge amount of effort in trying to figure this out. I do think, and I'm very optimistic around neurodegenerative disorders. There's just so many promising things.

包括像阿尔茨海默病这样的认知障碍吗？我认为早期诊断和早期治疗将是我们最先看到最佳效果的领域。这确实是一个难题。但对于帕金森病这种局部性问题，你可以再生那些细胞。所以你对运动障碍比认知障碍更乐观一些。

Including the cognitive ones like Alzheimer's? I think earlier diagnosis and earlier treatment is going to be the first thing where we're going to have the best effects. That is a really difficult one. But around Parkinson's where there's a focal problem, you can regenerate those cells. So you're more optimistic on the movement disorders than you are the cognitive disorders.

没错。部分原因是细胞损失的目标非常集中。我们可以通过手术获得细胞。当我们谈论阿尔茨海默病时，情况就有点棘手了，因为它同时涉及大脑的多个系统。甚至有一些研究使用电刺激大脑中对记忆编码非常重要的部分。

That's right. Partly it's because the target in the cell loss is very focal. We can get cells through a surgery. When we're talking about Alzheimer's, it's a bit trickier because it involves multiple systems in the brain simultaneously. There are studies even using electrical stimulation in parts of the brain that are really important for encoding memory.

这些方法很有前景，但我认为对于这些真正的阶跃函数，每个人都希望要么阻止疾病发展，要么逆转它。这需要更多时间。但我确实认为早期检测将改变游戏规则。有点跑题了，但这是通过安妮的故事引出的。你对导致人们面临椎动脉夹层风险的因素有什么看法吗？

These things are promising, but I think for these really step functions, everyone wants is to either stall disease or reverse it. It's going to take more time. But I do think that early detection is going to be a game changer. A little off topic, but it's come up through the story of Anne. Do you have a point of view on things that place people at risk for vestibular artery dissections?

例如，不管是不是无稽之谈，出于某种原因，我一直害怕让任何人调整我的颈部，因为担心会发生椎动脉夹层。这个风险有道理吗？考虑到这种损伤概率低但严重性极高，人们还应该注意其他什么事情吗？这不是无稽之谈。实际上有统计证明，某些类型的颈部整脊动作可能导致椎动脉壁损伤。

For example, for whatever reason, whether it's just a wives' tale or not, I've always been afraid of having anybody ever adjust my neck for fear of having a vestibular artery dissection. Is there any truth to that as a risk? Are there other things that people should be aware of given the low probability but very, very high severity of such an injury? It's not a wives' tale. It's actually statistically proven that certain kind of chiropractic movements around the neck can cause an injury to the wall of the vertebral artery.

夹层这个术语意味着动脉壁发生了分层。血管壁通常有多层结构。夹层发生时，血管受损，血液开始进一步分裂动脉壁，直到血管闭塞。所以这是一个非常危险的情况，就像你说的，发生在脑干的关键部位。因此我们通常建议不要进行剧烈的剧烈运动。

And that term dissection means that the wall of the artery has dissected. There's usually multiple different layers to that vessel wall. And what happens with the dissection is the vessel's injured, and then blood actually starts splitting the wall of the artery more up until the point where it becomes occluded. And so it's a very, very dangerous situation, and like you said, a critical part of the brainstem. So generally, we recommend not severe aggressive movements.

但有时你可以在体育运动中看到这种情况，当颈部周围发生高速运动时。所以这些是其他可能发生的情况。话虽如此，这种情况发生率非常低。是的。概率很低。是的。

But sometimes you can see it actually around sports, where you have a very high velocity movement around imposture, around the neck. And so those are the other cases where you can see it. That being said, this is very low incidence. Yeah. Low probability Yeah.

发生的概率。还没有到可以告诉人们避免某些体育运动之类的程度。如果我们能把哈维·库欣从坟墓中复活，今晚你就能和他共进晚餐。你认为如果他看到自己创建的领域现在的发展，他会说什么？我认为他有一部分会看着我们做的一些手术，我们仍然在做开颅手术。

Of happening. It's not at the level that you could really tell people to avoid certain sports or anything like that. If we could bring Harvey Cushing back from the dead, then you could have dinner with him tonight. What do you think he would say if he saw what was going on in the field that he created? I think that there would be one part of him that is looking at some of the surgeries that we do, where we're still doing craniotomies.

而休会说，这看起来和我们一百五十年前所做的非常相似。我认为这是他天才的一部分。我们仍在这样做的事实意味着它仍然有效，而且仍然安全，能让人们渡过难关。这其中很多功劳要归于库欣医生。

And Hugh would say, that looks pretty similar to what we did one hundred and fifty years ago. I think that's part of his genius. The fact that we still do it means that it still works, and it's still safe, gets people through. A lot of that credit goes to Doctor. Cushing.

但有些事情我认为他根本无法想象，比如我们现在取出血栓来逆转中风的方式，我们在脑机接口方面的工作，解码大脑活动，为瘫痪者替换交流的思想基质——我认为这在当时是很难真正想象的，主要是因为我们的知识如此有限，电子技术也远未达到能想象现在所能实现的事情的水平。所以我们看到的很多东西实际上依赖于已经发展的技术，比如人工智能。我们在解码大脑方面做的很多工作即使在我们拥有硬件（可能十年前或二十年前，甚至更早）也无法实现。解码直到现代机器学习出现才成为可能。这些事情现在正以非常非常快的速度加速发展。

But there will be things that I don't think he could have ever conceived, the way that we're retrieving blood clots that are reversing strokes, what we're doing with brain computer interfaces, decoding brain activity, the substrate of thought to replace communication for people who are paralyzed, I think that that would have been very hard to really imagine back then, primarily because our knowledge was so limited and electronics was nowhere even close to being able to imagine what could be done now. So a lot of what we're seeing actually relies on technology that has evolved, like artificial intelligence. A lot of the work that we did on decoding the brain just couldn't work, even though we had the hardware maybe ten or twenty years ago, probably even earlier than that. The decoding was not possible until this modern machine learning. These things are just accelerating very, very fast right now.

当我还是住院医生时，我墙上曾挂着一张非常著名的照片，是霍普金斯医院五位可以说是创始医生的照片。当然，有外科的霍尔斯特德、内科的奥斯勒，我想凯利是妇科的，还有一位病理学家。当然，库欣在去哈佛之前是霍尔斯特德的学徒。老实说，如果你能把他们所有人都复活到今天，看看他们各自的领域进步了多少，我认为库欣会是最震惊的那个，因为——也许我错了，会有历史学家纠正我——但我真的认为我们今天讨论的事情，正如你所说，是难以想象的。当然，奥斯勒会看到他从没想象过的药物。

When I was a resident, I used to have this very famous picture on my wall of the five physicians who were sort of the founding physicians at Hopkins. So of course you had Halsted in surgery and Osler in medicine and I think Kelly was gynecology and then there was a pathologist. And of course Cushing was the understudy of Halsted before he left for Harvard. I honestly think if you could bring all of them back to life today to see how much each of their fields had progressed, I think that Cushing would be the one most blown away because, and maybe I'm wrong and some historian will correct me, but I really think that what we've talked about today is, to your point, unimaginable. So, of course, Osler would see medications that he never could have conceived of.

他根本无法想象GLP-1激动剂及其对减肥的深远影响。他当时也绝想不到会有一种药物可以根除胆固醇，更不用说每六个月注射一次就能做到。他那时甚至可能都没想过肥胖症。说得好。尽管他当时在尝尿液，所以他肯定知道……但确实，我认为思维上的飞跃到了我们现在的位置——不过话说回来，也许病理学家也从未想象过我们今天能对肿瘤进行的基因组测序。

He could never conceive of a GLP-one agonist and the profound effect it could have on weight loss. He could never conceive at the time that there would be a medication that could eradicate cholesterol, let alone an injection once every six months that could do it. He might have not even conceived obesity back then. That's a good point. Although he was tasting urine, so he certainly knew about But yeah, I think the mental leap to where we are, although look, maybe the pathologist would have never imagined the genomic sequencing that we could do of tumors today.

当然，那时全是组织学。所以医学在一百年间的变化之大让我感到惊叹。当然，不难想象，如果我们这个物种一百年后还存在，下一个一百年将会带来更大的变化。绝对如此。我的意思是，现在的加速步伐是前所未有的。

Of course, back then it was all histology. So it is amazing to me how much medicine has changed in a hundred years. Of course, it doesn't take a leap to imagine that if we're still around as a species in a hundred years, the next hundred years is gonna offer far bigger changes. Absolutely. I mean, the pace of acceleration now is unprecedented.

我认为库欣会是最难理解现在发生的事情的人，根本原因在于我们谈论的是大脑。我们谈论的是一个我们才刚刚开始理解和把握其复杂性的器官系统。在过去一百五十年里，神经外科实际上主要是关于如何避免损伤大脑，如何从中取出肿瘤，如何处理管道系统（即血管系统、血液供应）。但如果你想一想，最大的开放性问题是现在乃至未来几十年真正要解决的。

The underlying reason why I think Cushing would be the one that would be the hardest to understand what's happening now is because we are talking about the brain. We are talking about an organ system that we're just starting to fathom and put our heads around sort of the complexity. For the last one hundred and fifty years, neurosurgery has really actually been about how do you avoid injuring the brain, How do you take a tumor out of it? How do you deal with the plumbing, which is the vascular system, the blood supply? But if you think about it, the biggest open ended questions are really being addressed right now in the coming decades.

大脑本身是如何工作的？然后我们如何利用这一点来解决各种各样的神经和精神疾病？神经外科的历史实际上主要是试图避免损伤，保持在大脑外部等等。现在则更向内看，试图真正理解这个系统、这个器官是如何工作的。这是一个非常激动人心的时代，因为每次我们解锁大脑某个部分的基本功能时，极有可能就会产生一种疗法，无论是通过脑机接口还是通过新的生物学方法。

How does the brain itself work? And then how do we tap into that to address a large variety of neurological and psychiatric conditions? The history of neurosurgery was actually primarily about trying to avoid injury, stay outside of the brain, etcetera. Now it's much more inward looking, trying to understand actually how the system works, how the organ works. And it's a super exciting time, because every time we unlock essentially a function of a certain part of the brain, there's a very high probability that there's going be a therapy, either through a brain computer interface or through a new biological approach.

每当我们解锁一种新的机制，就会有相应的治疗方法出现。这就是未来的景象。我做这个播客的一个隐藏议程，就是鼓励尽可能多的年轻人投身医学。我理解如今医学作为职业的吸引力远不如二十年前、三十年前、五十年前，最优秀的人才通常都流向了其他领域。但我希望像这样的播客，以及我与医生们做的许多其他节目，能够真正展示出我们需要最优秀的人才进入这个领域。

Every time we unlock a new mechanism, there'll be something that we can do to treat it. And that's what the future's going to look like. One of my hidden agendas of this podcast is to encourage as many young people as possible to go into medicine. And I understand that today medicine is not nearly as attractive a career as it was twenty years ago, thirty years ago, fifty years ago, and that the best and the brightest are typically going elsewhere. But I think a podcast like this, as are many of the podcasts I do with doctors, I really hope it showcases that we need the best and the brightest to go into this.

再次强调，这并不是说我们不需要另一个杰出的人才去做人工智能、投资银行、法律或其他顶尖人才去的领域。但选择医学职业确实有机会改变文明的轨迹，而你所做的，Eddie，正是站在这一前沿。尤其是它将科学、医学和技术的所有学科融合在一起的方式，真的非常令人兴奋。谢谢，Peter。

And again, this is not saying we don't need another brilliant person doing AI or investment banking or law or wherever else the top people go. But there is really an opportunity to bend the arc of civilization by choosing a career in medicine and what you're doing, Eddie, is really on the forefront of that. Especially the way it combines all disciplines of science, medicine and technology. It's just super exciting. Thanks, Peter.

是的，我也对此感到非常兴奋。谢谢你的到来，我真的很感谢这次讨论。谢谢邀请我。

Yeah. I'm really excited for that too. Thanks for coming. I really appreciate this discussion. Thanks for having me.

感谢收听本周的《The Drive》节目。如果你想深入了解这一期内容，请访问 peterateyahmd.com/show-notes。你也可以在 YouTube、Instagram 和 Twitter 上找到我，用户名均为 Peteratea m d。你还可以在 Apple Podcasts 或你使用的任何播客播放器上给我们留下评论。本播客仅用于一般信息目的，不构成医学、护理或其他专业医疗服务的实践，包括提供医疗建议。

Thank you for listening to this week's episode of The Drive. Head over to peterateyahmd.com forward slash show notes if you want to dig deeper into this episode. You can also find me on YouTube, Instagram, and Twitter, all with the handle Peteratea m d. You can also leave us review on Apple Podcasts or whatever podcast player you use. This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing, or other professional health care services, including the giving of medical advice.

不形成医患关系。使用本播客的信息及相关材料风险由用户自行承担。本播客内容无意替代专业医疗建议、诊断或治疗。用户不应因自身任何医疗状况而忽视或延迟获取医疗建议，并应就任何此类状况寻求医疗专业人员的帮助。最后，我非常严肃对待所有利益冲突。关于我的所有披露及我投资或顾问的公司，请访问 peterateamd.com/about，我在那里保持了一份最新且活跃的所有披露清单。

No doctor patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice from any medical condition they have and they should seek the assistance of their healthcare professionals for any such conditions. Finally, I take all conflicts of interest very seriously For all of my disclosures and the companies I invest in or advise, please visit peterateamd.com forward slash about where I keep an up to date and active list of all disclosures.