In this episode, my guest is Dr. David Linden, Ph.D., professor of neuroscience at Johns Hopkins University School of Medicine and the author of many popular books about the brain. We discuss individual differences between people — focusing on differences in how people sense the world around them and the roles that chance, heredity, and life experiences (even in utero) play in determining our physical and cognitive traits. We discuss the bidirectional connection between the mind and body and how our thoughts and mental practices (e.g., meditation and breathwork) impact our health. We also discuss the link between inflammation and depression. We also discuss Dr. Linden’s terminal illness diagnosis, his mindset during chemotherapy and what his diagnosis has taught him about the mind, gratitude, time perception and life. This episode also covers sensual touch, cerebellar function, and epigenetic inheritance and ought to be of interest to all interested in neuroscience, genetics, psychology and human development. 
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Timestamps
(00:00:00) David Linden
(00:03:59) Sponsors: ROKA & Levels; Huberman Lab Survey
(00:07:54) Sensory Touch & Genitals, Krause Corpuscles
(00:16:46) Sexual Experiences & Sensation
(00:19:14) Human Individuality & Variation; Senses & Odor Detection
(00:30:25) Sponsor: AG1
(00:31:22) Visual Individuality; Heat Tolerance; Early Life Experiences & Variation
(00:40:28) Auditory Variability, Perfect Pitch
(00:42:08) Heritability & Human Individuality: Cognitive & Physical Traits
(00:49:36) Heritability, Environment, Personality; Twin Studies
(01:00:12) Sponsor: InsideTracker
(01:01:19) Development, Chance; Transgenerational Epigenetic Inheritance
(01:07:37) Single Generation Epigenetic Inheritance & Stress; Autism
(01:15:52) Sleep Paralysis; Cerebellum, Prediction
(01:23:47) Nature vs. Nature, Experience; Linden Hypothesis
(01:30:37) Mind-Body Interaction; Chemical Signals
(01:39:10) Inflammation & Depression
(01:43:35) Neuroplasticity, Inflammation & Mental Disorders; Microglial Cells, Exercise 
(01:52:15) Fads & Science
(01:55:16) Mind-Body Communication; Cancer 
(02:03:28) Mind-Body, Mediation, Breathwork
(02:07:30) Atrial Fibrillation, Synovial Sarcoma, Heart 
(02:14:22) Gratitude & Anger; Chemotherapy, Curiosity & Time Perception
(02:19:58) Death, Brain & Future Prediction, Religion & Afterlife
(02:24:15) Life Advice; Time Perception & Gratitude
(02:34:35) Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Momentous, Social Media, Neural Network Newsletter
Title Card Photo Credit: Mike Blabac
Disclaimer

Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life.

I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine.

David Linden is a professor of neuroscience at Johns Hopkins School of Medicine.

His laboratory has studied neuroplasticity, that is how connections in the brain change in response to experience.

Much of that work focused on a structure called the cerebellum, which is also sometimes referred to as the mini brain because it looks like a mini brain in the bottom and back of the human brain.

And it's responsible for an enormous number of basic functions that we use in everyday life, including our motor behavior, that is our ability to walk and talk, but also dance, play instruments, and it's responsible for an enormous number of basic functions that we use in everyday life, including our sense of balance, our ability to learn new motor behaviors, as well as our sense of timing.

Today, we will discuss the cerebellum and what it does, but Dr.

David Linden will also teach us about the important sense of touch, as well as what makes us different as individuals.

The reason today's discussion encompasses so many important topics is that Dr.

David Linden's laboratory has focused on many of those topics.

And he is also the author of 5 excellent popular books about neuroscience that focus on, for instance, our sense of pleasure and where it originates from and what controls it in the brain, as well as our sense of touch.

And today we start off our discussion by talking about the recent discovery of a set of neurons that have been known about for a long period of time, but that only recently have been characterized that are involved in sensual touch in particular.

And it's a fascinating conversation, I assure you.

David Linden informs us about what makes us individuals, how each and every 1 of us perceives the same things differently.

And it's an absolutely fascinating conversation, which tells you, for instance, why some of you think a smell is putrid, indeed smells like a vomit, whereas others perhaps are not bothered by that smell and why others still are attracted to that smell or something that you look at or something that you hear.

We also talk about nature versus nurture and how we come to be who we are, not just through our genes and epigenetics, but also through our early childhood experience and adult experience.

And then in the latter third of our conversation, we shift to talking about the so-called mind-body connection and the science underlying how our thoughts inform our bodily health or lack thereof, as well as how the organs of our body control the chemicals, hormones, and thoughts within our brain.

David Linden himself and the fact that in 2020, he was diagnosed with a form of heart cancer that led his physicians to tell him that he had 6 to 12 months to live.

Now, obviously, because he was in our studio to record this conversation, he has outlived that prognosis, but he lives day to day with the knowledge that his death may very well come soon, although it isn't clear exactly when that day will come, of course.

He tells us how the initial prognosis of his cancer, as well as outliving that prognosis, has informed his day-to-day life, as well as his thinking and his relationships.

And that leads to a very direct and frankly emotional conversation that includes advice on how all of us can get the most out of our daily living and out of our overall life.

It's an extremely powerful conversation that I believe everyone, regardless of age or health status, can benefit from.

And it's 1 that makes clear that not only is Dr.

David Linden a spectacular scientist, but also a spectacular educator, a spectacular popular writer, a spectacular family man, including husband and father and friend to many people and his colleagues, but he is also a courageous and spectacularly generous human being.

Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford.

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And as always, thank you for your interest in science.

I've been looking forward to our conversation and we have a lot to talk about.

Lots of different aspects of science, lots of different aspects of personal journey and what you're confronting now, as it relates to your health and your future.

I wanna start off with a question that I learned from the 1 and only, the great Karl Deisseroth, who was the first guest on this podcast, my colleague at Stanford.

And for those of you that don't recognize Karl's name, he is a absolute phenom.

So he's an MD and he also is a bioengineer who's developed a lot of the modern tools for probing the brain.

And anytime I've met with Carl, the first thing he says is,

So I'm gonna steal that approach and say, what

gonna steal that approach and say, what are you most excited about lately?

Well, very, very lately, the most interesting thing that I read in neuroscience is the answer to a scientific problem that I think is really dear to a lot of people's hearts and that is what are the nerve endings in the genitals that are responsible for sexual sensation?

And you know if you think about it right people can feel sexy from being touched on lots of different parts of the body.

But there's something special about the genitals.

Doesn't matter male or female or intersex or gay or straight or bi or whatever you are, you know, the genitals are a hot spot.

And you'd think as biologists we'd know this by now.

This would be something we could just answer.

there was a German neuroanatomist named Krauss, and he cut thin sections of tissue from the penis and the clitoris, and he looked at them under the microscope.

And he saw a particular kind of nerve ending there that has since been called the Krauss corpuscle.

And there were lots of them in these 2 places.

And so he thought, well, maybe this is the cellular basis of sexual sensation.

Maybe these are the particular nerve endings that are responsible for this.

But there were some things that were in favor of that and some not.

So these nerve endings are also in some other places that people can find more or less sexy, like they're in the nipples and they're in the lips and they're in the anus, all places that get popular in that domain.

But they're also in places like the cornea, or the lining of the joints.

So the distribution doesn't quite make sense.

And so if you wanted to really test, as a scientist, Whether these nerve endings are responsible, you want to record their electrical signals while the genitals are being touched.

You'd want to inactivate these cells and see if you could interfere with sexual sensation.

And this, in a preprint from David Ginty's group at Harvard is just what they have been able to do in mice.

They found a way to label and record from and activate and inactivate artificially the Krauss corpuscles.

And so you see a nerve ending in the skin, it could be conveying all kinds of information.

It could be tuned for hot or for cold or for itch or for pain or for inflammation or for mechanical sensations, stretching, vibration, indentation.

And sure enough, when they recorded from these Krauss corpuscles, they really are mechanical sensors, as you would expect, if they were involved in sexual sensation.

And then the other thing, then what they did is they tried to artificially turn them on.

And so the way they did that is they used genetic tricks to express 1 of Karl Deisseroth's molecules that activates neurons when blue light is shown on them.

And they found that if they express this artificial protein in the Krauss cells in a male mouse and then shine blue light, the mouse gets an erection.

Well, if you turn them off in a male mouse, it's just as interested in females when they're in heat, But it won't mount and thrust and ejaculate as much.

And if you turn them off in a female mouse, during the time of her cycle where she would normally be sexually receptive, you find that she is much less interested.

She's much less likely to let him finish.

So this is the remarkable result that finally, after all these years, since 1860, Now we know what the nerve endings are that convey sexual sensation.

And like all good science, then, you know, there are a lot of questions that are really interesting to our everyday lives.

Like, you know, people like different things in bed and have different propensity for orgasm or like to be touched in different ways.

Well, is part of that reason because of individual variation in their Krauss corpuscle structure?

We know that sexual sensation diminishes with aging.

Is that in part because Krauss corpuscle density is lost from the skin of the genitals?

And that's a reasonable idea because we know, for example, that fine touch sensors in the fingertips, so-called Merkel and Meissner endings, also named after German anatomists like so many things are, are also lost with age.

So This finding from Ginty's lab has opened up a whole world of science.

And I've been, my own lab doesn't work on touch, but I've been a fanboy of touch for many, many years, mostly because where I work at Johns Hopkins Medical School, There have been many terrific touch researchers.

And I hear about it over lunch, and I got all fired up.

So years ago, I wrote a book about it, and I still follow the field.

And this is the most interesting thing in that field recently.

And as I recall, Ginty was your neighbor at Hopkins before he moved to Harvard.

He was 1 of the ones, Ginty, Stephen Hsiao, Michael Caterina, Xinzhong Dong.

There have been a number of world leaders in the cellular basis of touch sensation at Hopkins.

Do you recall if in the preprint that you were describing, there was an experiment where they activated these Krauss corpuscles

I sent that exact email to David Ginty and they said they are in the process of doing that right now and they don't quite know yet.

And so I asked him, I said, so for example, is erection of the clitoris even a thing in mice?

So we're activating the Krauss corpuscles in female mice, and we're just kind of staring at it and looking and see if anything happens.

They don't even quite know what it is they're looking for because it's that much on the leading edge of things.

Yeah, or perhaps the female mice would be more willing to mate outside of the usual time frame of receptivity if these Krauss corpuscles are stimulated.

Because I think that the hormonal regulation of receptivity is like a sledgehammer and very hard to overcome.

But they might be more willing to continue mating or mate for longer during their fertile time.

And I just wanna remind people, because we had a guest recently, Dr.

Rina Malik, who's a urologist, reproductive and sexual health expert, she's an MD.

And she made clear that the clitoris and the penis come from the same embryonic origin.

They are analogous tissues in different individuals.

I do have 1 more question about this sexual touch thing.

So these are not of the brain and spinal cord.

And my understanding is that peripheral neurons regenerate and can remodel themselves extensively in ways that neurons within the brain and spinal cord tend to remodel less, especially as 1 gets older out of the so-called critical period.

Is it possible that these cross corpuscles and their patterns of innervation within the genitals change according to the stimulation that people experience?

In other words, is sexual sensation experience dependent?

And so we don't know, because monitoring this in people is not technically possible, right?

And it could be for a couple of different reasons.

In other words, it could be, I think, what you're imagining is that there's actual structural plasticity.

If you looked at these Krauss corpuscles, that you would actually see them changing their shape or their size or their density as a result of experience.

But what can also happen is a phenomena like desensitization.

That is to say when there's stimulation for a long time, then the receptors transiently can become less sensitive to touch.

And it's well known, particularly in males, that chronic masturbation can produce desensitization of sexual sensation in the penis.

And that could be as a result of a physical change, a morphological change in the Krauss corpuscles, but it's more likely to be a change in their function that you wouldn't be able to simply see by looking at an outline of their structure in the microscope.

And I'll have to check out this preprint.

I'm also a huge fan of David Guenti's work and colleagues.

There are many people involved in that domain of work, of course.

I'd like to talk about your recent book and the sort of underlying basis of what led you to write it.

And what intrigued you about this idea of human individuality?

The book, Unique, is 1 that we'll provide a link to in the show note captions.

And it's a very interesting idea that we are all different, especially coming from a neuroscientist who we were trained at least similarly to learn that, sure, the bumps and ripples of the brain and the fine wiring of the brain is different and we are all unique and different.

We have different shapes, aka morphologies, but focusing on human individuality is not something that modern neuroscience or classic neuroscience has really done much of.

It's really focused on how people do X or people do Y this way.

Tell us about unique and tell us about human individuality.

Yeah, well, I mean, you're absolutely right.

So when I look at the experiments in my own lab, how do we do them?

Do we work on mice with genetic variation?

We work on highly inbred mice that are designed to be as genetically similar to each other as possible.

And then We raise them basically in prison in little cells, which may not be a good idea.

And we try to give them as similar experience as possible.

They are given toys and food and water, but I agree, it resembles a prison of sorts.

They have nothing like the experience of a wild mouse, let me put it that way.

And yes, there are, as you said correctly, there are plenty of experiments where there is enrichment for mice.

So For example, in our lab, when we put running wheels in the cages of our mice and let them run overnight, they're active at night, your average mouse will run 2 kilometers in a night for a little tiny mouse.

And some of the mice are so intense, they will run 20 kilometers.

Imagine a mouse doing 20K, but it will happen.

They want to exercise, and they're really bored.

So Yes, to get back to your general point, so much of science is designed to try to find general principles of function of the brain, of physiology, of genetics, and to ignore individual variation.

But individual variation is so important to our human experience and actually is so important to the process of evolution and natural selection and how species make their way in the world, that it's something that requires a lot of attention.

And to me, what's really fascinating is that when you look at the variation in the way sense organs function, it's almost a miracle that we can agree on a common reality at all, even within the human species.

And this is true of some senses more than others.

Obviously, in your world, in the retina, we have various kinds of loss of color vision that are well known, and some other more complicated phenomena having to do with impairments in the perception of motion or form.

But the place where this really happens is in the olfactory system.

functional receptors for different odorant molecule smells in our nose.

And if you sequence the genomes of many people, you find that the DNA that encodes for these odorant receptors is unusually variable from individual to individual.

As a matter of fact, If you take 2 different people, on average, they will have functional differences in

And if you do as Leslie Vossall and her colleagues did at Rockefeller University and give odor tests where they give people different things to smell, and then they dilute them and find the threshold at which they can detect them.

You find enormous changes from people to people, both in general terms.

Some people are just better smellers than others.

But in terms of individual odors as well, there are some odors that some people can't detect and other people smell 1 way.

For example, there is a secreted hormone called androstenone.

Androstenone, there are some people who can't smell it at all.

For some people, it smells like rather pleasant, like cut grass, and for some people, it smells foul, like urine or sweat.

It just depends on genetic variation in 1 particular odorant receptor.

Another phenomenal researcher who studies olfaction, among other things, Catherine Duloc, I once heard say that some people have a gene that for them makes the smell of microwave popcorn, they experience that smell as vomit.

And other people who lack this gene like the smell of microwave popcorn, or at least for them it's not aversive.

Well it can, and actually that's a very particular funny case.

So the relevant chemical there is butyric acid and also isovaleric acid.

And so there are researchers, I think Rachel Hertz is 1 of them, who have given a mixture of these 2 chemicals to people.

And if they say, this is Parmesan cheese, they go, oh yeah, that's Parmesan cheese.

And if they give it to other people and say, this is vomit, they'll go, oh yeah, that's vomit.

And if they tell people, They give them 1 vial and say, this is Parmesan cheese.

And then they say, well, actually, we fooled you.

They're convinced that they couldn't have been the same thing.

So this points out not only is there genetic variation that is responsible for how individuals perceive odor.

But we are incredibly suggestible in terms of odors.

And we are very dependent upon them in terms of cultural context, and this can be learned.

And this is central to our humanity in the sense that we humans are what I like to call the anti-pandas.

Pandas live in 1 spot in southern China, and they eat 1 thing, bamboo.

Humans can live in any ecological niche in the world, from the tropics to the poles.

And humans eat a wide, wide, wide variety of foods.

And as a result, it means that we have to have a very plastic olfactory system.

There have to be very few things that we find innately aversive.

There are only a handful of odors, rotting meat odors.

Molecules with the evocative names like cadaverine and putrescine are things that even babies when they're newborn find aversive.

But other things happen that they need to be learned.

For example, pretty much every adult finds poop odors unpleasant, but babies happily play with their own poop.

They have to learn that that's disgusting.

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Dr. David Linden: Life, Death & the Neuroscience of Your Unique Experience