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Neuroscientist breaks down 3 bizarre mind-body phenomena — and their medical impact
Neuroscientist David Linden sheds light on the biology behind phenomena that medicine has long struggled to explain, from voodoo death and broken heart syndrome to the placebo effect, and why grief shows up in autopsy results.
Timestamps
00:22 Chapter 1: The connection between mind and body
06:45 Chapter 2: Hacking the hunger system with GLP1
12:42 GLP-1 and the new era of appetite control
20:03 Modern food engineering vs. ancient biology
21:43 Chapter 3: Voodoo death, broken heart syndrome, and placebos
22:14 When belief becomes biology: Voodoo death & misdiagnosis
27:00 Broken hearts, placebos, and the power of expectation
31:08 The placebo effect
37:09 From mind-body science to medicine: Devices, drugs, and the future
40:32 Chapter 4: How our brains fight cancer
42:00 Cancer, the nervous system, and ‘the way of the nerd’
58:35 Chapter 5: How a neuroscientist prepares for death
Transcript
The below is a true verbatim transcript taken directly from the video. It captures the conversation exactly as it happened.
I’m David Linden. I’m a professor of neuroscience at Johns Hopkins University School of Medicine. For many years my laboratory has studied neuroplasticity that is how the brain and the nervous system are changed as the result of experience in the world.
Chapter 1: The connection between mind and body
So like a lot of biologists I’ve been resistant to the idea that our mental life affects our body profoundly because for so long it seemed like something that was untestable and ethereal and operated in a different realm from biological science. But my father was a psychiatrist and he told me when talking here psychiatry works it doesn’t work in some magical psychological realm that is divorced from biology it works because it changes your brain and the same is true of any behavioral process whether it is meditative practice or psychotherapy or controlled breathing or what have you. These things aren’t working in the ether. They are working through biology and in just the last ten years our understanding of that biology has gotten a whole lot better.
So it’s not as if that all claims that have been made through history about mind body medicine will turn out to be true and will turn out to be understandable but a subset of them that seemed supernatural at one point will turn out ultimately to have real biological explanations.
So much of our understanding of both daily functioning and things going wrong in disease right now is focused on the body by itself. There is now a revolution where we’re realizing that many disease processes and many things that we do every day from sleeping and waking to eating food and being hungry – things like cancer autoimmune disease – these are things that we are now learning are strongly under the control of the brain and when things are under the control of the brain it’s not just something that happens subconsciously it means we have the option to control them with our behavioral practices whether these are breathing practices meditative practices psychotherapy exercise – it opens up an entire new way to think about disease.
Maybe this would be a point to talk about interception and extraception. So when we think of the senses we tend to think of smell, taste, vision, touch, hearing things that are pointed outward towards the world that give you information about the world around you but we also have inward pointing so-called intraceptive senses or senses of self that tell us things like is my bladder full, is my bowel full how is my head in relation to the force of gravity. These intraceptive senses are crucial to the ongoing conversation between mind and body.
If these signals need to be seen really fast then they are conveyed electrically from neurons that run from the body up through the spinal cord and get to the brain. If they are signals that can work more slowly then the body can secrete a hormone the hormone passes through the blood system this is a slower process ultimately it makes its way to the brain and binds receptors on neurons or other cells in the brain to produce a slower effect.
Yet another interesting way is that the brain is continuously responding to our breathing rhythm and our heartbeat so every pulse of the heart has a very slight effect on dilating arteries in our brain which our brain can then sense and act upon and that’s a very rapid signal these are the ways that the body talks to the mind and of course the mind as instantiated in the brain will speak back through many other mechanisms some of them being neural signals and there are a couple of different kinds of these some are the volitional or somatic motor system so when you have a thought and you say “I want to raise my arm” and you raise your arm that’s something that we all know about and that’s something that is conveyed from the mind to the body in a conscious way but they’re also subconscious ways and signals flowing and this involves something called the autonomic nervous system and this is mostly a phenomenon in which the mind controls the body at a level that’s below your level of consciousness, the autonomic nervous system is in turn divided into two general branches the sympathetic nervous system which people say prepares you to fight or flee or the parasympathetic nervous system which prepares you to rest and digest and so as you can imagine the parasympathetic and the sympathetic nervous systems are somewhat in opposition they’re yin and yang so to speak of the way the mind controls the body subconsciously.
There are other ways too so the mind control the can control the body through the release of hormones that are released by the brain. They effect places like the pituitary gland and the adrenal gland which secrete still more hormones and these are conveyed through the circulatory system broadly to all sites in the body so they tend to have broadcast at general effects. So hormones, neural signals, and then the third way is through control of the immune system and through these are through a class of specialized hormones for the immune system molecules called cytokines
Chapter 2: Hacking the hunger system with GLP-1
So we think of eating and hunger as being a very straightforward thing. “Oh yeah, if you’re a little hungry, I eat something, now I don’t want to eat anymore” but it’s really complicated and it involves a lot of continual dialogue between the body and the mind using both the senses that are pointed out at the world and the senses that are pointed inward at the body. So, if you can imagine walking down the street in New York City near little hungry and you smell some pizza, “That smells good” and the first thing you’re doing is you’re making a decision – am I hungry? Do I want to go seek out where this odor is coming from? “Oh yes, I do,” so you’re using interceptive information to say yes my stomach is not distended and full of nutrients and I feel hunger, it’s been a while since I last ate so I’m interested in this idea. You’re using your memory to say “Oh yes, I remember that I like pizza. That’s a food that I enjoy” and so these smells are bringing up positive associations and that is influencing your decision to go seek it out. And then let’s say you order a slice and you have it in your hand and you’re looking at it and you’re seeing it so you’re taking in information with your eyes you’re smelling it and then you’re making a decision, “Do I want to put this in my mouth or not?” and if it smells a little off if you sniff it and you think it might have spoiled or the oil is rancid or something bad, you’re gonna say “Well no, maybe I won’t put that in my mouth after all.” But really, eating this a series of decisions. So now let’s say you’ve taken a bite and you go “Oh, that’s delicious, yes I’m tasting the salt, I’m tasting the fat, I get that nice yeasty thing from the crust, there’s also mouth feel in my mouth, I’m I gonna swallow this bite” and you’re saying “Oh yes this is palatable food, there’s nothing wrong with it and so I won’t spit it out, I’ll swallow it” – that’s yet another decision.
And then you’re going on eating your slice perhaps you’re walking down the street and you have to make a decision “Am I getting full? This slice is enormous. Am I gonna finish it or am I gonna chuck some of it in the trash and leave it be?” And that decision uses several different streams of information coming from your body. It’s using fast neural signals from your stomach that are saying how distended is my stomach? How much has it swollen as a result of food filling it up? And it is also using fast information from the stomach there cells in the lining of the stomach that evaluate the nutrient content of the food. This is why you can’t just drink a lot of water, for example, distended your stomach and then suppress your appetite that doesn’t work as a diet strategy. Your stomach knows what’s inside. It can tell the difference between water and food and it can even tell what kind of food is there – is it fatty? Is it proteinaceous? Is it carbs? That sort of information saying “Oh yes there are proteins there, there are fats there, there’s a fairly high level of them” and these are signals that go rapidly to your brain and inform the decision “Should I terminate this meal and stop eating? Or should I should I keep going a little while longer?”
And then say 20 minutes later, when you are making a decision do I want to eat again, there are yet other sensors in not your stomach but in the first part of your small intestine that are evaluating the nutrient content of the food as it passes there and saying you know “I just ate, I have plenty of nutrients. I have a feeling of fullness. I’m not going to eat again for a while.” How does that happen? Well that is a slow hormonal signal and when food is sensed by particular neurons in the lining of the small intestine, they secrete a hormone and the hormone is called glucagon-like peptide-1 (or glp-1) and this hormone has several effects. It acts on receptors in the stomach to slow gastric motility, so your stomach empties less quickly, but more importantly it goes to centers in your brain that control your appetite and they suppress your appetite for tens of minutes or an hour or two afterwards.
So we all know that if you put sweet food in your mouth it tastes sweet and that the reason for that is that on your tongue and in your oral cavity there are special sensors for sugars, but what most people don’t know is that there are similar sensors for sugars actually in your stomach and in your small intestines and those sensors send information to your brain to guide decisions like should I stop eating food right now.
Curiously though while artificial sweeteners that are widely used and sodas and other foods, they do a very good job of mimicking real sugar for the sweet sensors that are in your oral cavity, they don’t fool the sensors that are in your stomach and your intestines because those in sensors are molecularly different. So what that means is when you eat artificial sweeteners there’s a mismatch. Your mouth is telling you “Oh this is sugar!” But your gut is saying “No, I don’t think so, this isn’t real sugar” and as a consequence your brain is getting conflicting signals and this is probably some of the reason why artificial sweeteners are really not a very effective strategy for losing weight.
GLP-1 and the new era of appetite control
If you haven’t been living under a rock for the last few years, you’ve heard that there are very popular diet drugs that are based upon the hormone GLP-1. Now, GLP-1 is a class of molecule called a peptide – it’s a short bit of a protein – and these peptides are broken down very quickly in your bloodstream so when your small intestine secretes GLP-1, that signal is only acting on your brain very briefly and so you would need to inject many times a day and it it’s not wouldn’t be an effective drug. But some clever chemists at the drug company Novo Nordisk realized that you could take the natural GLP-1 molecule and hang chemical groups off the side, in particular you could hang fatty acids off the side, and these fatty acids cause this GLP-1 like molecule then to bind to a protein in the blood called albumin. And when it’s bound to albumin, it’s much more resistant to being degraded by enzymes, and it’s much more resistant to being immediately excreted by the kidney.
As a result, while natural GLP-1 acts for only minutes, this modified GLP-1 that makes a GLP-1 based drug can suppress appetite for a very very long time. It can live for a long time in the bloodstream and as a consequence, you can use it to make a drug that you inject once a week and suppresses appetite strongly. I’m talking about things like semaglutide, which is known as Wegovy or Ozempic, or Tirzepatide, which is known as Zepbound or Mounjaro, and these drugs by mimicking this natural signal are very effective at suppressing appetite and people are losing typically between 12 and 17 percent of their body weight after taking a once a week injection of these drugs over many weeks.
But, they seem to be even better than that. In other words, if you compare the health benefits that you can measure from people who are taking GLP-1 drugs, it seems that there are beneficial effects above and beyond what you would predict from just the amount of weight they’re losing. And we don’t entirely know why this happens, but it makes sense biologically because the receptor for the hormone GLP-1 which is also going to be activated by these drugs, it’s not just in your stomach and it’s not just in your brain, it’s in all kinds of organs. It’s in your heart, it’s in your kidneys, it’s in your liver, it’s in all kinds of places, and it’s doing something good there. We don’t entirely know what that is, but it’s probably some sort of anti-inflammatory effect that provides benefit beyond just what the weight loss is doing.
GLP-1 based weight loss drugs aren’t perfect. They have a lot of benefits, but they have some side effects. Some people feel nauseated, some people feel gastrointestinal distress, sometimes people feel brain fog or a loss of energy on them. And the newer generations of weight loss drugs that are being developed right now may help to make those side effects better.
The other thing is that when you eat less, you don’t just lose fat mass, you also lose muscle mass, so you got to be really careful if you’re losing weight on a GLP-1 drug. You want to go to the gym and do load bearing exercise to keep your muscle mass up, you want to make sure that you’re consuming enough protein to allow your muscles to be able to continue to stay at a reasonable size, so some of these problems may only emerge when we see people using them for years and years and years. And you have to use them for years and years and years because they only work as long as you consume them. You go on a GLP-1 drug, you use it for a year, you go off the drug – you’re gonna gain all the weight back. It doesn’t seem to have a permanent reversal effect.
When these drugs were first developed if you would ask to me as a neuroscientist would these drugs that suppress appetite also suppress the other kinds of rewards that people tend to overdo, like alcohol or drugs of abuse, or even compulsive shopping or gambling – all of which activate the brain’s reward circuitry – I would have guessed no.
I would have said there’s gonna be a separate circuit for appetite and there are reasons to keep that apart from the general reward circuitry. But the indications are that this is not entirely the case. So, it’s early days, but there are promising indications that the GLP-1 based weight loss drugs have some effectiveness for helping people to control their alcohol consumption and to help them get off of psychoactive drugs, and maybe even to deal with compulsive behaviors that are making problems in their life, like compulsive shopping or compulsive gambling. It’s gonna be really interesting to see how this plays out in research in the next few years.
So there are some really interesting things that have come out in the last few years in body-to-brain signaling that have implications for weight loss. One of them has to do with exercise. we know that when you exercise intensively it stimulates appetite and so some people think “Well, you know I might go to the gym and work out real hard, but then I’m gonna be a real hungry and then I’m gonna eat a lot of food, and maybe there won’t be a net benefit.”
It seems to be though, that intensive exercise does have a net benefit. The amount that it stimulates your appetite doesn’t entirely compensate for the amount of weight that you burn through the intensive exercise.
Why is that? Well part of it seems to be that when you have very intensive exercise you produce a metabolite called lactate. It becomes conjugated in your body with an amino acid called phenylalanine and this conjugated compound seems to act through a rather complicated biochemical cascade in the body to get to the brain to suppress appetite itself. So, intensive exercise really does seem to be a good thing to do.
Very few people can lose all the weight they want to lose from intensive exercise itself, but it is very, definitely, a benefit, and of course it has myriad benefits well beyond weight loss and looking good. It has benefits for your mood, it has benefits for maintaining your cognitive function as you age, there’s all kinds of great reasons to want to exercise intensively, but weight loss is one of them.
Modern food engineering vs. ancient biology
Since 1960, the average person in the United States is 27 pounds heavier. That’s a lot. Why is that? It’s not that the genetics of people in the United States has changed. It’s not like there’s a toxin or there’s a change in our metabolism. The reason for this is the people who are making our highly processed foods, as we find both in restaurants and also in the supermarket, have laboratories where they figure out how to manipulate our appetite systems in our bodies and brains in order to get us to overeat.
And we have an evolutionary history, right? Through most of our time as humans, there have been intermittent famines. Food has often been scarce, so it has made sense in those situations, if you come across of very highly caloric fatty food or something really sweet, it made sense to snarf it all down and to put on a little weight so that the next time there was a famine, you might survive and make your way through it.
There is a mismatch though, most people in the world, and certainly people in the United States, don’t live in that famine-laden environment anymore. And as a consequence, when food service corporations, through clever engineering, override our natural inclinations to eat and stop eating with specially engineered foods, they are exploiting this ancient circuit in our brains that says “Pack on the fat pack, on the sweet so that you can survive to live another day.”
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