- What did you mean when you said that the skull is a poor adaptation and a titanium plate will be better? And in particular, what does that mean in reference to things like traumatic brain injury? I mean, are human beings unnecessarily vulnerable at the level of traumatic brain injury because our skulls are just not hard enough?

- You know, maybe I'm being too harsh about skull. The skull is very good at what it does, given the tools that we are working with as biological organisms that develop in our mother's uterus. The skull is, you know, usually the appropriate size. It's one of the hardest things in your body.

That said, there are a couple of puzzling vulnerabilities. Some of the thinnest bone in the skull is in the temporal region. This is, you know, neurosurgeons will all know that I'm heading toward a feature that sometimes darkly is called God's little joke, where the very thin bone of the temporal part of the skull has one of the largest arteries that goes to the lining of the brain right attached to the inside of it.

And so this bone just to the side of your eye tends to fracture if you're struck there. And the sharp edges of that fractured bone very often cut an artery called the middle meningeal artery that leads to a big blood clot that crushes the brain. That's how a lot of people with, you know, otherwise would be a relatively minor injury end up dying, is this large blood clot developing from high pressured arterial blood that crushes the brain.

And so why would you put the artery right on the inside of the very thin bone that's most likely to fracture? It's an enduring mystery, but this is probably the most obvious failure mode in the design of a human skull. Otherwise, you know, in terms of general impact resistance, I think the brain is a very hard thing to protect.

And the architecture of human anatomy probably given all other possible architectures that can arise from development, it's not that bad really. One of the interesting features in terms of shock absorption that hopefully prevents a lot of traumatic brain injury is the fluid sheath around the brain. The brain you may know is, it's mostly fat.

It floats in saltwater in our brains. Our brains are all floating in saltwater. And so with rapid acceleration, deceleration, that sheath of saltwater adds a marvelous protective cushion against development of, you know, bruising of the brain, say, or bleeding in the brain. And so I think for any flaws in the design that do exist, you can imagine things being a lot worse, and there's probably a lot fewer TBIs than would exist if a human designer was taking a first crack at it.

As you describe the thinness of this temporal bone and the presence of a critical artery just beneath it, I'm thinking about most helmets. And here, I also wanna cue up the fact that, well, whenever we hear about TBI or CTE or brain injury, people always think football, hockey, but most traumatic brain injuries are things like car accidents or construction work.

It's not football and hockey. For some reason, football and hockey and boxing get all the attention. But my colleagues that work on traumatic brain injury tell me that most of the traumatic brain injury they see is somebody slips at a party and hits their head or was in a car accident or environmental accidents of various kinds.

To my mind, most helmets don't actually cover this region close to the eyes. So is there also a failure of helmet engineering that I can understand why you'd wanna have your peripheral vision out the sides of your eyes, periphery of your eyes, but it seems to me if this is such critical real estate, why isn't it being better protected?

- You know, I'm no expert in helmets, but I don't think we see a lot of epidural hematomas in sports injuries. To get this kind of injury, you usually need a really focal blunt trauma, like the baseball bat to the head is a classic mechanism of injury that would lead to a temporal bone fracture and epidural hematoma.

With sports injuries, you know, you don't often see that, especially in football with a sharper object coming in contact with the head. It's usually another helmet, right, is the mechanism of injury. So I can't think off the top of my head of an instance of this exact injury type in sports.

- You spent a lot of time poking around in brains of humans. And while I realize this is not your area of expertise, you are somebody who I am aware, you know, cares about his health and the health of your family. And I think generally people's health. When you look out on the landscape of things that people can do and shouldn't do, if their desire is to keep their brain healthy, do any data or any particular practices come to mind?

I mean, I think we've all heard the obvious one, don't get a head injury. If you do get a head injury, make sure it gets treated and don't get a second head injury. But those are sort of duh type answers that I'm able to give. So I'm curious about the answers that perhaps I'm not able to give.

- Yeah, well, you know, the obvious ones, it's one that you talk about a lot. And I see a lot of the smoldering wreckage of humanity, you know, in the operating room and in the emergency room for people that come in. You know, I work my practices in San Francisco right next to the Tenderloin.

And so a lot of people that end up coming in from the Tenderloin have been drinking just spectacular amounts of alcohol for a long time. And their brains are, you know, very often on the scans, they look like small walnuts inside their empty skull. There's so much atrophy that happens with an alcohol soaked brain chronically that I would say that's, you know, far and away the most common source of brain damage that many of us just volunteer for.

And it's, you know, when you look at the morbidity, kind of the human harm in aggregate that's done, it's mystifying that it's not something that we are all paranoid about. - People will think that I don't drink at all. I'll occasionally have a drink. I could take it or leave it, frankly.

If all the alcohol on the planet disappeared, I wouldn't notice, but I do occasionally have a drink, maybe one per year or something like that. But I am shocked at this current state of affairs around alcohol consumption and advertising, et cetera. When I look at the data, mainly out of the UK Brain Bank, which basically shows that for every drink that one has on a regular basis, when you go from zero to one drink per week, there's more brain atrophy, thinning of the gray matter cortex.

You go from one to two, more thinning. You go from two to three, and there's a near linear relationship between the amount that people are drinking and the amount of brain atrophy. And to me, it's just sort of obvious from these large-scale studies that, as you point out, alcohol atrophies the brain, it kills neurons.

And I don't have any bias against alcohol or people that drink, I know many of them, but it does seem to me kind of shocking that we're talking about the resveratrol and red wine, which is at infinitesimally small amounts. It's not even clear resveratrol is good for us anyway, by the way, a matter of debate, I should point out.

But so alcohol, certainly alcohol in excess is bad for the brain. - Sure. - In terms of, okay, so we have head hits, bad, alcohol, bad. You're working, as you mentioned, you're the tenderloin. Is there any awareness that amphetamine use can disrupt brain structure or function? - You know, that's not an area that I've spent a lot of time researching in.

I, you know, I incidentally take care of people that have used every substance known to man in quantities that are, you know, spectacular, but I haven't specifically done research in that area. I'm not super well-versed on the literature. - I ask in part because maybe you know a colleague or will come across a colleague who's working on this.

There's just such a incredible increase in the use of things like Adderall, Ritalin, modafinil, R-modafinil, which I think in small amounts in clinically prescribed situations can be very beneficial, but let's be honest, many people are using these on a chronic basis. I don't think we really know what it does to the brain, aside from increasing addiction for those substances.

That's very clear. - Well, for better or worse, we're generating a massive dataset right now. - Well put. I'd like to briefly go back to our earlier discussion about neuroplasticity. You made an interesting statement, which is that we are not aware of any single brain area that one can stimulate in order to invoke plasticity, this malleability of neural architecture.

Years ago, Mike Merzenich and colleagues at UCSF did some experiments where they stimulate nucleus basalis and paired that stimulation with a eight kilohertz tone, or in some cases, they could also stimulate a different brain area, the ventral tegmental area, which causes release of dopamine and pair it with a tone.

And it seemed in every one of these cases, they observed massive plasticity. Now I look at those data and I compare them to the kind of classic data. I think it was Carl Ashley that did these experiments where they would take animals and they'd scoop out a little bit of cortex, put the animal back into a learning environment, and the animal would do pretty well, if not perfectly.

So they'd scoop out a different region of cortex and a different animal. And by the end of maybe three, four years of these kinds of lesion experiments, they referred to the equal potential of the cortex, meaning they concluded that it didn't matter which piece of the cortex you took out, that there was no one critical area.

So on the one hand, you've got these experiments that say, you know, you don't really need a lot of the brain. And every once in a while, a new story will come out where a person will go in for a brain scan for some other reason or an experiment, and the person seems perfectly normal, and they're like missing half their cortex.

And then on the other hand, you have these experiments like the stimulation of basalis or VTA, where you get massive plasticity from stimulation of one area. I've never been able to reconcile these kinds of discrepant findings. And so I'd really like just your opinion on this. What is it about the brain as an organ that lets it be both so critical at the level of individual neurons and circuits, so, so critical, and yet at the same time, it's able to circumvent these, what would otherwise seem like massive lesions and holes in itself?

- Yeah, I mean, a lot of it, to reconcile those experiments, you first account for the fact that they're probably in different species, right? You take out a particular portion of a pig or a rabbit brain, a small amount, you might not see a difference, but a small portion of a human brain, say the part most interested in coordinating speech or finger movement, and you're gonna see profound losses or visual cortex, right?

Take out a small portion of V1 and you'll have a visual deficit. And so species matters. Age matters. If you take out half of the brain in a very young baby, that baby has a reasonable chance of developing a high degree of function by having the remaining half subsume some of the functions lost on the other side, because they're very, very young and their brain is still developing.

It's to some degree a blank slate with extremely high plasticity over many years. So that can overcome a lot of deficits. Taking an adult animal's brain that isn't very well differentiated functionally to begin with, you might not see those deficits. So apparently there's a lot of redundancy as well, right?

There's a lot of say cerebellar and spinal circuits in other animals that generate stereotyped behavior patterns and might not need the brain at all to perform say a walking movement or some other sequences of motor activities. So a lot of that depends on the experimental setup. I would say in general, adult humans are very vulnerable to losing small parts of their brains and losing discrete functions.

(upbeat music) (upbeat music) (upbeat music)