[informal chatter before the start, not transcribed]

Welcome and introductions

Max Rodman: Welcome, everybody. All right, guys, thank you so much for coming. This is the first edition of what we’re calling MVMT Talks. A very exciting edition.

I don’t know if we ever squared this circle. We met through a contact of Jeff’s. Jeff was my original contact into speaking to one of the centres at Yale. Then we got connected to Rajita, and we discussed some research that got put on pause but that we hope to do. Joe is Rajita’s husband and also in the field of academia, science and medicine. And John and I met a few years ago at a lunch.

John Krakauer: Long ago.

Max Rodman: Long ago, yeah. So we are very fortunate that Rajita and Joe are visiting Lisbon and agreed to the invite to come and speak. We are also very fortunate that John agreed to come and join the party. And finally, extra fortunate that Jeff, an old friend, one of our members and a man of many talents, has agreed to moderate the panel. So, to the first of many MVMT Talks. Thank you guys so much for coming, and over to you.

Jeff Krone: Welcome. I’m just going to give a brief introduction. If there’s anything I get wrong, feel free to correct me. Then I’ll go into some questions and we’ll see where it goes, and we can open it up to questions from the audience. Sounds good?

John Krakauer: Sounds good to me, yeah.

Jeff Krone: So here to my right we have Dr John Krakauer, who’s a neurologist and neuroscientist, and one of the world’s leading researchers on motor learning and recovery after stroke. He is the John C. Malone Professor of Neurology, Neuroscience, and Physical Medicine and Rehabilitation at Johns Hopkins University, where he directs the Brain, Learning, Animation, and Movement Lab, and an external professor at the Santa Fe Institute. Here in Lisbon, he directs the Champalimaud Foundation’s Centre for Restorative Neurotechnology, which brings together neuroscience, technology and medicine to develop new treatments based on behaviour. He co-created a therapeutic game for stroke rehabilitation that is now used clinically. He is also known for a widely discussed argument that neuroscience cannot understand the brain without carefully studying behaviour.

Then we have Rajita Sinha, a clinical psychologist and clinical neuroscientist. She is the Foundations Fund Endowed Professor of Psychiatry and Professor of Neuroscience and Child Study at Yale School of Medicine. She is the founding director of the Yale Interdisciplinary Stress Center, which studies how stress and trauma shape the brain and body, and why some people cope resiliently while others become vulnerable to addiction, chronic pain and chronic disease. Her lab has shown how cumulative life stress is linked to changes in brain regions that govern emotion and self-control. She develops new treatments for chronic stress and relapse, and received the Research Society on Alcoholism’s Distinguished Researcher Award in 2020.

And then we have her husband, Dr Joseph Guarnaccia, a board-certified neurologist who has practised for more than 30 years, specialising in multiple sclerosis. He trained in neurology at Yale and directs the Multiple Sclerosis Treatment Center at Griffin Hospital in New Haven — New Haven, Connecticut?

Joe Guarnaccia: Close. Derby, Connecticut.

Jeff Krone: He is also a consulting neurologist and research physician with the Yale Stress Center, where he has worked on mindfulness for sleep in people with MS and cannabis-based approaches to chronic pain. In 2015 the National MS Society inducted him into its Volunteer Hall of Fame.

If there’s anything I got wrong, please feel free to say so. But I’m going to jump right in, and you can all answer this in your own time. Can you share a little about how the work you’ve been doing for all these years relates directly to movement?

How their work relates to movement

Rajita Sinha: I’m happy to start. I’m really happy to be here, and thank you all for coming. I love what you said about Dr Krakauer: that you cannot understand the brain without behaviour. As a psychologist and neuroscientist, I totally share that view. In neuroscience and in psychology, we’ve moved very much into cognition. And that’s great — understanding, problem solving and all of that — but almost to the detriment of ignoring behaviour. So that has been our segue into movement and behaviour.

My own personal journey, and why I think movement is so important, is that I was a trained Indian classical dancer growing up. Movement played a really important part in my own development, and in some ways saved me through the adolescent traumas and crises that adolescence is often filled with. But really, it was learning how emotions connect to the body in a way that is critical for the experience of emotion, for understanding emotion and for problem solving.

So behaviour has been a really important cornerstone of the subjective experience of stress, but also of the subjective experience of wellness. Our work has journeyed through stress, making movement and behaviour one of the four pillars of experience, and understanding that as critical for resilient coping. That’s how I would start.

John Krakauer: Well, it’s not fair, because movement is what I study — you should have let me jump in first. So yes, I do motor control, motor skill learning, recovery from motor injury. My academic career has been very much there.

But I’ve also been very interested in the cognitive–motor interface. In other words, most of what we admire movement-wise is cognition-dependent. You do not have a chimpanzee Olympics.

There’s an irony at this particular juncture. AI is talked about incessantly: problem solving, AlphaFold, AlphaGo. Each large language model, each foundation model, is managing to do more and more impressive cognitive feats. So we’ve got this cognitive infatuation on the artificial side, whereas a lot of humans have sort of given up on thinking. It’s all about moving, psychedelics, emotions, embodiment. So we’ve got this very odd thing going on, where thinking is going out of fashion in the biological world, whereas it’s the obsession in the artificial world. I’m not making a judgement here, I’m just making a statement.

With respect to stress, neurological conditions, psychiatric conditions, mental health conditions, there’s no question that movement-based interventions are beneficial — even in the cognitive domain. That’s the other irony. Despite the divide I just described, on the therapeutic side, if you want a cognitive benefit, movement is a very effective way to get purely cognitive benefits. So the ironies multiply. My interest is very much now at that interface between — [trails off]

Joe Guarnaccia: I come at this mostly from a disease treatment perspective. MS generally occurs in younger people than stroke does. Mobility has always been the biggest concern of patients with MS. They’re younger, and they’re concerned about how they’re going to be walking in five, ten or fifteen years.

Fortunately, in MS our therapeutics have undergone revolutionary change in the last ten years or so. We have a lot of very effective ways of stopping the progression of the disease and stopping disease activity. But a lot of our concern now is: once you’ve treated the disease, how do you make people’s lives better — help them with movement, as well as other domains? So we use a variety of approaches, and rehabilitation comprises a significant amount of my time.

Neuroplasticity: what it is and isn’t

Jeff Krone: There’s a common word that’s thrown around almost like a buzzword: plasticity. Sometimes I feel it’s become associated with all kinds of things, whether it’s psychedelics or movement. In what ways does it actually play a role in the work you’re doing? What does it really mean to each of you, and how do you see it misused?

John Krakauer: Well, I will answer that question —

Jeff Krone: Go for it.

John Krakauer: — because I know this has all been rigged. It’s one of the most irritating notions imaginable. Most people who say it have no idea what they’re talking about.

So let’s be very clear. If you go right down to the heart of what it means: for a system — let’s say a synapse or a circuit — for the same input, you now have a new output. Some structural change occurred so that there is a new output for a given input. That happens; otherwise you wouldn’t be able to learn Portuguese if you’re not a native speaker, or learn a new sport. So it’s a life force, in a way.

Now, when people say things like “rehab is there to use neuroplasticity to make you better”, those are the kinds of banalities one has to avoid, because nothing is actually being said. The other problem is you hear these terms: the brain is rewiring, the brain is remapping, the brain is reorganising, one area of the brain is taking over from another. It’s all nonsense.

So you have this irony. Yes, plasticity exists. There are structural changes in the brain with experience that change the output: you become more skilled, you learn something. That’s undeniable, and it’s a fascinating field. But when that ubiquitous property of both biological and artificial neural networks gets carried into the disease realm, you get all these odd words: reorganisation, remapping, rewiring, takeover. I’ve written a lot about how that is just not the case.

So what you have to ask is: how do you use the more garden-variety plasticity, which does exist, to get recovery, without interposing these new terms that have an almost magical quality? And that’s not a downer, because it turns out that garden-variety plasticity can get you a long way — with exercise, with training, with rehab, with brain stimulation, with pharmacology like psychedelics. One just has to be rigorous and sober about the term, rather than it turning into a folk term that people wield almost like religious terms. One has to be more nuanced in order to be excited about it.

Rajita Sinha: I would agree. Neuroplasticity is the biggest buzzword, and there’s a newer version of it that maybe some of you have been hearing — it’s been thrown at me, especially in the psychedelic world: “neuroplastogen”. So you have plasticity, but oh my goodness, there may be things like psychedelics that are plastogens that will promote rapid rewiring. And I totally agree with John: that’s nonsense.

That comes from human brain science. What we love to do is put people in an MRI scanner, and you can see brain regions light up. If you take a psychedelic drug, very quickly you’re going to see some lighting up. But let me tell you, a lot of drugs do that. It’s not just psychedelics. They’ve really captured the imagination with this neuroplastogen idea, as in promoting neuroplasticity.

But, consistent with what John has been saying — and now I’ll put my psychologist hat on — I really think it’s a new framing of what we know about learning. Learning builds on skills and practice and rehab. Whether it’s a drug you’re taking and suddenly the brain is lighting up — “this is the potential for new connections that might get you there” — it’s not going to get you there if you take that drug once, which is what people are thinking. You take a plastogen once, you’re in a therapy session, and you’re going to see all these new connections in your life. How is that going to translate into something consistent, day to day, ongoing? Are you going to stop drinking, for example, if you have an alcohol use disorder, or if you drink and want to cut back? No, it’s not going to do that. There’s a lot more that goes into it.

So I like to think of it as learning being a key, critical process in how the nervous system works — and a lot of biological systems — certainly at the synaptic level, the neuronal level, and then in connections. Whether it’s a psychedelic or the practice that you all do, and we all do as much as we can, it is literally building out, through movement and through practice, training the mind in different ways — whether it’s movement or cognition — to get to your goal.

Psychedelics, critical periods and the two-step approach

John Krakauer: Just a little caveat to that. Psychedelics are another obsession of the moment — AI, psychedelics [inaudible] — so weird, the things. But psychedelics are very interesting. There’s no question the obsession is slightly justified. And I think it’s extremely important to understand that there’s a very interesting dichotomous debate going on in the psychedelic world.

We’re doing a psychedelic trial right now, and it’s based on the notion that psychedelics, along with some other drugs, can reopen critical periods. Critical periods are periods, often in development but they can happen even in adulthood, where your ability to change structurally with experience — the gain on that process — is heightened. For example, we and others have shown that after stroke, your ability to respond to training is much greater early on than later, because the critical period closes.

Now, psychedelics — fascinatingly, and we’ve done some work at Hopkins on this — can reopen critical periods. Gül Dölen, a neuroscientist who was at Hopkins and is now at Berkeley, has done remarkable work showing that in an adult rodent you can reopen the critical period for early socialising. So that’s all plasticity-based.

But the other thing psychedelics do is give you these weird, bloody experiences, right? And at the moment there’s a paradox in the link between an experience you can have once and plasticity that has to accumulate over time. It’s not clear where the bulk of the credit should go for the effect psychedelics have on clinical conditions: the experience or the plasticity. That debate has not been resolved. They may not be mutually exclusive; there may be some subterranean connection between them that we don’t fully understand. Nevertheless, you can have one remarkable experience in a single moment, but training has to take place over time. So you’ve got this diachronic–synchronic conflict. Kind of fascinating, right? And at the moment — I’d be interested to hear what you say — the experience side is getting a lot of play over the plasticity side, wouldn’t you say? How that debate resolves, we’ll see.

Joe Guarnaccia: I have a question. In terms of experimentation with psychedelics, what would be the connection with actual movement?

John Krakauer: Well, there is one. I would say that if it’s true that psychedelics open critical periods, then you could imagine a two-hit, two-stage approach: you prime and open the system.

I’ll tell you about our psychedelic trial; I might as well mention it. We’re doing a trial at Hopkins using psilocybin in chronic stroke patients — in other words, people whose natural critical period window has closed. You give them an infusion of psilocybin, and they have to be an inpatient for a day. Then they do three weeks of the game you mentioned that I co-invented — a kind of digital psychedelic. You’re basically a dolphin in the ocean, moving, eating fish, avoiding sharks. It’s cognitively challenging, cardiovascularly challenging, and it’s skill learning.

So, to your question: you open the system for maximum susceptibility to movement-related training, and then you train on top. It’s a two-step process. And if you’re doing something like a sport, which is both cognitive and motor, you hope you’re getting a cognitive opening as well as a motor opening, both proceeding under this transiently — or not so transiently — opened critical period. That’s what we’re doing. It’s kind of the Wild West. In animal models we’ve shown that it can work.

And there are studies, by the way, that have shown this even on cognitive testing. A researcher [name heard as “Andrew Conway”; to verify], who was at Princeton and is now in New Mexico, did this wacky study where healthy people did three types of training: they played brain games on a computer, they were on a treadmill, or they wrestled. Then they looked at cognitive outcomes — selective attention, working memory, executive function — and the wrestling group won hands down, on a purely cognitive evaluation.

Now, I’m not saying you should all start wrestling with each other. But the point is that whether it’s a dolphin, boxing or tango, this mixture of thinking and moving seems to have a multiplicative effect over thinking alone — brain games — or moving alone — the treadmill. There’s something magical about the combination.

One last point: exercise and gaming have slightly different consequences for mental health and cognition. For being anxious, depressed or stressed, exercise seems to be more effective, whereas something like a sport or gaming seems more effective on the cognitive side. It’s all early days, but it is interesting.

Resilience, recovery and the two-stroke mouse study

Jeff Krone: Fascinating. So bringing these together seems to be a good method for developing oneself, getting the cognitive and the cardiovascular and physical benefits. That brings me to the next question, about resilience and specifically recovery. I came across these mouse studies from your work, where mice who experienced a first stroke were then able to recover — they experienced two strokes. Can you explain this better than I can?

John Krakauer: It was a wacky result, actually — one of the top three things that drive people a bit mad. The idea was that a stroke, as I said, can reopen a critical period. We know that after a stroke there’s a period where you do most of your recovery.

So, with Steve Zeiler, we had this idea. We gave a mouse a stroke and then we waited — we basically recreated the time you spend on a stroke unit before you go to rehab. The mouse had a stroke, we waited, they transferred it from the ICU to the rehab unit in the mouse world, and it didn’t recover very well. If we started rehabilitating immediately, within 24 hours of the stroke, it completely recovered. That’s interesting — that’s the critical period idea. It’s just shorter in a rodent.

But then we did something I think was kind of wild. We said: maybe what we need to do to treat the mouse’s first stroke, once it’s outside the window, is to treat its first stroke with another stroke. Now, it’s not going to work very well for us [inaudible]. And sure enough, we expanded the infarct size, and the animal was now worse again. But then we started rehabilitating immediately after the second stroke, and it completely recovered from both.

In other words, you had reopened the critical period after you’d been too late to exploit it with the first stroke, and you used the second one, even though you paid the price of a larger stroke. Actually, at something I was speaking at in New York years ago — it had to be New York, obviously — a filmmaker came up and said we should make a movie where people are willing to have little strokes so they’re suddenly in a critical period again. So instead of The Matrix, where you put glasses on, you have little strokes. I don’t know what happened to that.

Jeff Krone: I think that would go down very well.

John Krakauer: No, no. But that wasn’t really resilience. That’s something you’re much more expert in. I’m very interested in it. I don’t really have any idea why some people seem to do better than others with seemingly the same lesion and the same initial deficit. I’m interested in robustness and resilience and how to treat it, but it’s not my area.

Unidentified panellist: I’m going to take this to a pathological level: what happens when you section those brains — the mice?

John Krakauer: Well, it’s an interesting question. We do look, actually. If this is the region that had the stroke, and you then train in the critical period, or when you reopen it, this other region — the premotor region, which also projects to the spinal cord — upregulates. You see a change in the inhibitory–excitatory ratio in a region that isn’t adjacent to the stroke. It’s almost like it received a phone call saying, “Hey, we’re in trouble here.” So this region strengthens its connection down to the spinal cord, because by reducing inhibition from interneurons relative to excitation, you can bring this residual architecture online.

It’s absolutely fascinating. But the interesting point is that to bring this residual architecture online after the other region has been damaged, you have to have the critical period open and do a lot of movement and training. If you reopen the critical period and don’t do the movement and training, you waste it.

Unidentified panellist: That sounds like a form of rewiring.

John Krakauer: No, it’s not — and it’s important. What you’re doing is increasing the gain on existing architecture that already has its axons and neurons in place. You haven’t, for example, sprouted new connections. What you have is a latent architecture, structurally intact, that needs to be stimulated — the two-hit process we were talking about. It has to be brought online.

It’s a bit like this: all of you are dominant in one arm. You’ve probably all tried to write with your other hand and asked yourself, why am I so rubbish at handwriting with this hand? But with practice you can get as good as you are on your dominant side, because you have the latent, relevant architecture to do it. So it’s not that you don’t use plasticity of the old kind — you strengthen existing synaptic connections. But you don’t suddenly transfer your right hand over to your left, or bring a new area online. You take that residual architecture and, through hard-earned practice, strengthen its pre-existing connections.

Rajita Sinha: I can take this a little to the resilience side, which also relates to your question, and I think it connects to recovery in an interesting way. Our thinking about resilience is broken down into your experience of movement and the motor system, the emotional system, the cognitive system, and what we call the interoceptive sensation system. Our lens, of course, is psychiatric disorders: cognitive and cognitive–emotional susceptibility and risk, how to rescue that, and how to build and strengthen it so you can prevent recurrence of illness.

We’ve learned from animal studies, but really the human neuroscience has given us much more perspective on complex psychiatric disorders. What we see is that there’s a lot of silencing happening in circuits. Things are getting quiet when they shouldn’t be — cognitive and attentional circuits, especially executive and metacognitive circuits. Our frontal regions are very tightly connected to emotion. They do a lot with emotion in terms of choice, evaluating situations, the decision to move: why am I going there?

What we’ve begun to see — and there is some overlap with psychedelics here — is what happens when you stimulate these multiple buckets of experience: motor, interoceptive, emotional, cognitive. If you’re suffering from depression or you’re in a depressive state, you have really tamped down experience. You can’t deal with it; you cannot have it. You’re not doing that consciously; that’s what has happened. Some parts you may be aware of.

What we want is to stimulate these buckets. In some ways it overlaps with what a psychedelic experience might be doing: stimulating the sensorium, internally as well as externally. A drug can do that. When you’re exercising, you’re using your motor system, but you’re also managing motor self-control — the decision to move one way or the other — in a very intricate way. There’s a lot of stimulation of multiple buckets. And not just stimulating the buckets in parallel: we can see through analyses in human neuroscience that you are increasing connectivity. Not just stimulation, but crosstalk.

We can break that down at a cellular and synaptic level, but our model has come to the point that to do that you also have to build tolerance in parallel. Because you’re also asking yourself to experience pain. Just as when you start a new training and use new muscles, you’re going to have pain. What do you all do with pain? You lean in and say, OK, I’m going to train more here, keep at it — and the pain starts to recede. That’s what rehab does as well.

So what about the psychiatric and emotional domain? Can we sit with the pain? A lot of the time therapy is about that, but you can’t tolerate it. PTSD is the other side of this: there’s so much hyperarousal that it’s intolerable and you have to run, do whatever it takes to get away from it. So the point is: how can we stimulate this in a way that is tolerable, and then expand the experience of tolerance so that you can build new circuits? That’s where we are with testing resilience models, both for preventing an illness and, mostly, for preventing its recurrence. It’s conceptually similar to stroke, though obviously very different in the actual circuits.

Interoception and stress

Jeff Krone: Earlier you mentioned interoception. Can you explain in your own words what interoception is, and how interoceptive awareness or accuracy relates to the mind–body connection, to psychiatric disorders or mental health in general, or to regulation of the nervous system?

Rajita Sinha: Thank you for bringing that up. I’m going to jump right in, because I study stress. A lot of the time, when people talk about interoception, they’ll say it’s your body telling you something, a signal from the body — which it is. But let’s think about stress. How do you know you’re stressed? What is stress for you?

Audience members: Tension. — Tension in your muscles. — Heart rate goes up. — Insomnia. — [inaudible] when you’re worried so much. — Racing mind.

Rajita Sinha: Tension, yes. Anybody else? Insomnia, OK. We’re now generating what I put in two buckets, but hold that thought. Racing mind, yes. So these are signals your body is experiencing. Maybe something came at you: you have an external sense experience of a stimulus that is stressful, or that came out of nowhere, and you start to feel your heart race, or tension, suddenly. Those are signals. How do you know they mean something? There’s a signal from your body going to your mind, and that’s interoception in the stress context.

You can see it in different ways. When you’re exercising, you feel your heart rate go up, and that’s interoception: an internal signal from your body to the brain. There’s a very clear pathway where it goes up, and as you trace it, and as we see the brain light up, if it’s doing the right thing it’s going to signal to motor areas. Because if a car was coming at you and your heart was in your mouth, what would you do? Run, right? You need to save yourself before you even think.

So there are these built-in circuits that may have become silent. That’s a dramatic example. I’m talking about the chronic stressors and situations we’re in where there’s no car coming at you, but you’re at work, you hate the person you work with, and you face them every day. That’s a chronic stressor. There are things you do to tolerate it, and they involve ignoring, avoiding, shutting down. Those are conscious things. There are also non-conscious, automatic things, where we don’t want to listen to our interoceptive signals, because it may not be workable in the moment. That’s the process by which we shut down these buckets of experience.

And yet what we want to do is the opposite. It feels paradoxical. But think about pain again. With pain, you have increases that feel intolerable. But when you sit with it — whether it’s cancer pain or physical pain — or you do something to tolerate it more, what happens? It actually starts to go down. It’s that same dialectic. So we come back to how we build resilience with buckets of experience. Interoception is a really key bucket, signalling all the way into the brain — not just to stimulate other parts of our system for action and protection, but also to build circuitry, to come up with meaning around it. That’s the other level, and it feeds back into resilience.

John Krakauer: Just one thing about the interoceptive system. It was an unexpected discovery of another sensory system. There were the senses — vision, hearing, touch, proprioception — and then, surprisingly, another system was discovered: small-fibred, unmyelinated, almost like the afferent component of the sympathetic nervous system. There’s the feeling of stress and then there’s the stress response, and the stress response, if it’s chronic, can be damaging.

And this was the system doctors had no sympathy with. A patient comes in and says, “I’m just not feeling right today, I’m feeling strange.” Well, that’s not one of the senses — dismiss. But it turns out you have this exquisite system. It can detect changes in pH, diapedesis of cells across the endothelium, the presence of a parasite. It’s quite remarkable. And it’s hooked up to the response you could subsequently have.

Somebody who has written really well about feelings and thinking together — and we’re in Portugal — is António Damásio. He’s got a new book that’s just come out. And this gets back to AI. The thing about AI is that it has no feelings. With our kind of cognition, everyone says, “Well, I feel this, I didn’t like that.” Our cognition is saturated with feelings and emotions. We have no idea how to do that in AI.

Two kinds of resilience

John Krakauer: And when it comes to resilience, I was interested in this. There are two types. There’s resilience of the body to disease. About 10–15% of people have fragility: they don’t do well in the setting of disease. For example, when COVID came along, there was mass death in northern Italy among the 70-year-olds, because they had no resilience. They had diabetes, hypertension, obesity, sedentary living, and they were just decimated. So there’s the question of why some people are resilient to physical disease.

Then there’s the resilience of people who seem able to deal with the knocks of life and get themselves back up again, while others don’t. I’ve always thought it has to do with being loved by your mother, reading books and having lots of sex. It seems to me those three would probably make you quite resilient on the psychological side. But I feel the psychological side of resilience and this physical lack of resilience are different things. Would you agree? Dying from COVID because you just don’t have robustness in your system, versus turning to alcohol when life gets too hard — are those two different uses of “resilience”? Or is there some subterranean connection?

Rajita Sinha: I think there is a connection. There’s a Venn diagram there. There’s a difference, because you’re talking about disease, and especially multiple illnesses that weaken body systems and nervous systems. But at the same time, the psychological is also connected to your body and your nervous system. At least that’s our frame of reference, and how I’ve talked about the buckets of experience. So I think there is an overlap. Why did those people die? We could break it down, and there’s a lot more that went on with having multiple illnesses.

John Krakauer: Diabetes, heart disease, the ability to fight a virus and manage that. When the news was coming out at the time — and then within a couple of years we did something remarkable, we made a very effective vaccine. What I found fascinating, and maybe you heard differently, is that in the news reports no one ever said: how come in a couple of years we came up with a very effective vaccine, but we haven’t treated the chronic conditions that made everyone so fragile in the first place? It never gets discussed. And it’s because it’s much harder to deal with chronic conditions than with acute, infectious ones.

*John Krakauer [speaker unconfirmed]**:* I think that gets back to movement, exercise, holistic things like here. It’s not going to be a vaccine that makes your life better. Wouldn’t we love to write a prescription — “make life better” — take it to the pharmacy?

Joe Guarnaccia: I just want to make one comment about that. Multiple sclerosis is a disorder of the immune system, and of course the immune system affects everything. A lot of patients can go for years undiagnosed but not feeling well. I think some of the conditions we see may have an underlying immune basis, some sort of perturbation. In some people it might manifest as MS; in others it might manifest as chronic fatigue syndrome, and so on. So we have to be aware that some people may have a genetic predisposition, or lifestyle issues, that produce a chronically unwell state, which can include pain and arthritis. We see a lot of these comorbidities in the patients I treat.

If you could prescribe one form of movement

Jeff Krone: On the topic of prescribing — not vaccines — if you were to prescribe one form of movement to everyone in this room, for brain health and overall longevity, what would it be, and how much, frequency-wise?

John Krakauer: Wrestling — you’ve got that one. I think I personally would say some kind of racket sport. Definitely. Don’t they show the longest lifespans? Just because it’s a combination of play; there’s another person involved, at least one; it’s cognitively challenging; it requires you to develop a skill; and it’s certainly exercise.

The other thing I would say is dancing — preferably disco dancing. I think that’s also great because you can get better at it, it’s communal, it’s certainly a workout, and you can learn multiple styles. So anything that combines socialising, skill, cognition and exercise is what I would definitely recommend. Taking up a new skill takes practice, so you have to do it. How much? I would say at least an hour or two of practice, at least three to four times a week.

And then the last sport: reading. Most people don’t read any more, and when they do, they read rubbish. So: reading hard books, and disco dancing [inaudible].

Rajita Sinha: Well, you took a couple of mine. And I’m not going to stay with one — he cheated, he took more than one, so I get to cheat too.

I was going to start with yoga — but a certain type of yoga, not all your regular yoga classes. I’ve given away where I sit with resilience: you want to stimulate these buckets. One of the ways we think of yoga is as a place where you can coordinate, integrate and synthesise breath with body and mind — all three. Attention with movement, and coordinating your breath, especially as you slow in and slow out. That’s part of yoga, even if it’s not necessarily what you learn in a regular class. I would say venture into that space, because you’re stimulating three of those four buckets, and hopefully the fourth, cognition, comes online as a function of doing it.

I’m obviously very partial to dancing, although I don’t limit it to disco. Coordinated movement — with singing, with engaging your mind, with really large- and small-scale movement — covers a lot of those buckets. And if you can do that, I don’t even think you have to do it three or four times a week. If you do it a couple of times, you’re going to find yourself doing better and better.

I’ll digress here, only to make the point that some of us may already have bought into exercise or movement or whatever helps health and well-being. A lot of people out there don’t have the time or information, and can’t really dedicate that time. So one of the things we’ve started to do is talk about building blocks: what are the small steps you can take and build on? Do you need to meditate for an hour, or two, or five, to get the benefits of meditation? We’ve started to talk about five-minute chunks, how often you do them to reset, then ten-minute chunks, slowly building the time. Not to say that’s enough or all you’ll need, but hopefully we begin to open your mind to wanting to do more. How did you feel? What was the experience like?

Same thing with dancing. Go have a big disco night — although I’m a little worried about disco, because there are lots of other things that go on when you go disco dancing. [laughter] John seems to know what I’m talking about; he’s getting a kick out of this. But starting slowly gets you to buy in — not because somebody is telling you, but because of how the experience makes you feel and what it’s giving you. So, dance in that way. And the third thing: I love reading, so I’d build on that. But those two things can go a long way if you think of movement.

Joe Guarnaccia: This isn’t exactly a prescription, but I’d just add that walking uphill is also a very good form of exercise. If you look at the blue zones, a lot of them — people living in different areas —

*Jeff Krone [speaker unconfirmed]**:* Yeah, I think that’s really fascinating. In Sardinia, they lived just like all the other people in the area, but this one group lived longer, with a greater concentration reaching a hundred. And really the only difference was that they lived on a very steep hill. So socialising, walking to meet people, and being on the —

John Krakauer: I hate to be a killjoy, but the blue zones have been entirely debunked. I can give you the references, but it’s all based on falsified birth records, unfortunately. But that doesn’t mean — I always think Lisbon is good for you, because there are hills. It’s also a great way to get rid of the elderly: those slippery stones.

Living with chronic neurological conditions

Jeff Krone: A question for you, Joe. You’ve followed people with chronic neurological conditions. In their recovery, what have you noticed is in a patient’s control and what isn’t? And where have you been surprised by the role of mindfulness or other non-drug therapies?

Joe Guarnaccia: I think it’s highly, highly relevant. I see a wide range of personalities as well as a wide range of disabilities. There’s a certain subset of patients who are concerned about their mobility on a daily basis. They work out every day; they’re very dedicated. They spend a significant amount of their day just trying to maintain their health, which is fascinating. I have patients who regularly run marathons, do mountain climbing — things that are very surprising. There’s a certain will there to make oneself better.

Of course, we try to help them with pharmacological treatments to enhance neurotransmission and to treat things like pain and fatigue. A lot of the movement issues in MS have confounding factors that we also deal with. But there is a certain subset of patients who are extremely dedicated.

Rajita Sinha: Can I ask a question? Do you see that those who are doing marathons and really investing in exercise — and maybe diet as well — end up using less of the pharmacotherapy, the immune therapies for MS? Do they have fewer relapses? Does the course of the illness change as a function of doing these things?

Joe Guarnaccia: It’s not clear, because everyone is on therapies, and everyone is getting new therapies. People who ignore that — and many people do — do so to their detriment.

Rajita Sinha: So the exercise is really more about their ability to function?

Joe Guarnaccia: These additional interventions are for their wellness. It’s hard to know; it’s a chicken-and-egg thing. People who are doing better can be more active, and are more active. People whose disease is more progressive have a tougher time doing that — but they still do it.

Audience Q&A: overstimulation and burnout

Jeff Krone: Maybe we can open it up to audience questions, if anyone has anything they’d like to ask.

Audience member: Speaking about the buckets of stimulation, and stress: when people are stimulated, or on a psychedelic trip, and they reach a full capacity of experience in those buckets, do they then enter a more depressive mode and the whole cycle starts over? Or do they need to bring themselves back down to the middle before they can start over? I’m not doing psychedelic research, but with depression, or even just people who are overstimulated with work or life — where all their buckets are almost at capacity, to the point of burnout — and then they crash.

Rajita Sinha: That’s a great question, because you’re thinking of overstimulation, and I’m glad you brought it up, because I want to clarify what I meant by stimulation. What you’re describing is a saturation point.

We do quite a bit of work on building out the adaptive stress response. Operationally, the adaptive stress response is: you have a low baseline. Your heart rate and everything is low; all the buckets are quiet. Then a stressor comes up and you have a nice reaction, because you want to respond to the stressor. And then you need to come back down. This needs to happen at multiple levels, but that’s the idea. What goes up needs to come down.

In your example of oversaturation, the baseline has shifted. It’s what we call pile-up mode: you’re at a high baseline, and there’s no room to go up any more. So you actually have a blunted stress response, which is very true in certain subtypes of depression, in anxiety, in addiction. There’s very new, interesting data showing that if you do a cardiac stress test on a treadmill and you have a blunted response because you’re saturated, it’s not good: it’s highly predictive of future cardiac events.

So with saturation, your baseline has shifted and you feel overwhelmed. But it’s not because you’re going up and down in your stress response. In fact you’re non-responsive: it’s a slow response, if any, and you’re not coming back to baseline. Think of a nice inverted U. You went for a run: you were at baseline, you went up, and you came right back down. If you’re saturated, you were already up, you didn’t really go up much more, and you didn’t come back down. The whole thing has shifted. Or you’re really low — childhood maltreatment, for example, really blunts the stress response.

In one subtype of depression we see this oversaturation. But I would not call that state “stimulation”. What I want to do in that state is slowly bring the baseline down, so that you can start to have a sensory experience, a stimulation experience that then comes back down. If you think of polyvagal theory, it’s more of a shut-down state, and you have to bring yourself back up. It’s a coordinated regulatory thing. In earlier times the idea was: shut everything down. That’s actually bad for the nervous system. We now know bad things happen for cognition, emotion and memory when you do that.

So you don’t want to shut anything down in this very linear way. What you want is better regulation, and dynamic flexibility: things going up and coming down, coming online when they’re supposed to and then settling. That’s the nervous system getting back its functionality. In the oversaturated state it’s rigid; it’s not moving in that way. Does that make sense?

John Krakauer: One way to think about it: the nervous system is good at acute responses — turning on and off, as you say. Peter Sterling, a neuroscientist at Penn, wrote a book I think everyone here should read, called What Is Health?. He’s a fantastic reductionist neuroscientist who became holistic when it came to health. Very interesting. His idea is that you can have a dynamic range of response, but if you’re constantly responding, the set point shifts. You change your set point, and then you don’t respond in the same way any more.

The classic example is blood pressure. You give a person an antihypertensive, they shift their set point, and you have to give them another antihypertensive. They shift their set point again and you have to give them a third. So we have patients on four or five antihypertensives. What you really want, as you’re saying, is to bring the set point back, rather than operating on the new set point. That means exercise, diet and a happy life.

So you have a direct contrast between drugs, which try to treat the condition by operating on the new set point, and doing something top-down — what Peter Sterling calls allostasis — where you shift the set point back again. That takes life changes. There are many examples where you can either go top-down, or you can find pharmacology.

Now again, psychedelics are weird, because everyone’s suddenly obsessed with taking drugs. Even people who love exercise and yoga and holistic things are obsessed with psychedelics. I find that really weird. In a sense, these drugs are a kind of [inaudible] experience: they’re drugs posing as something else. Where this leads, I do not know, but I find it kind of fascinating.

Audience Q&A: should you lean into stress?

Audience member: I’m super tired, so bear with me. You said it’s good to lean into it. I had this image of something [inaudible] coming up. What we usually do is park it, get shit done, and that’s it. You were saying lean into it — and if I have the space to do it, I can. But my story says that if I lean into it, I’m just going to get lost in it. I’m going to put too much attention on this stress thing. There are the voices of my parents saying: no, no, don’t spend too much time on negative stuff, on stressful stuff, just shove it away. So I’d love your perspective. What actually happens when we — [inaudible]

Rajita Sinha: Great question. Definitely, if you’re at work and it’s piling up, do what you’ve got to do to function. You need to get through the day. I think the vulnerability, or the risk, is what you said in the latter part: shove it away, don’t worry about it, keep working — it’s a great distraction. What are you doing with the feelings and the stress experience when you do that? Avoiding it, putting it away. It’s silencing.

When I say stimulation, I’m not talking about stimulating yourself to become hyper, leaning in and getting so immersed that you absolutely can’t function. That’s not it. Now I’m going to get into the mindfulness side of things. How about just noticing what’s happening? Noticing is a way in.

The way we deal with the buckets of experience is: how do you know you’re stressed? You say, “Oh my god, my heart was just beating,” or, especially at work, “I’ve been doing five things at once and my mind feels flooded.” That’s a very common experience for people at work with five deadlines. So what would you do? The first thing is just to stop. We have an acronym, STOP. S stands for stop, or slow down. Then take a breath.

Now, you may not want to do that at noon or 1pm. You may need to wait until 5pm. Maybe it was a bad day and that evening you don’t want to do anything either. But at some point, if you keep shoving it away, it’s going to catch up with you. You’ve all heard that. So the idea is that you stop and slow down when you can. Not five things: one thing. And the first thing is literally checking in with yourself.

When you check in, you take that breath — that’s the T. Then you observe the buckets of experience. You might have felt your heart beating fast, and you weren’t going to bother with what emotion you were feeling, or with all those negative thoughts: you’re not going to make it, you’re going to fail at this, your boss is going to scream at you, whatever it is. And any other sensations. So just observe and notice those things. This is just one small exercise to start the process.

By noticing, you’re letting each of those buckets have its due. “OK, I’m feeling warm, or tense” — whatever you’re experiencing on the interoceptive side. What’s the feeling that comes with that? There might be anxiety. If nothing else comes, don’t worry about it. But start to notice, and you might see that the anxiety brings negative thoughts with it: “I’m not going to make it.” Or, like your parents said, “Keep working and don’t bother with the emotions, because emotions screw you up.” Whatever these voices are that climb quietly into our minds and that we shove away — let them come up. They’re just thoughts. They’re living somewhere in your mind and body.

Allowing them, giving each bucket its due, actually lets you experience the situation you’re in. Is it that bad to say “I’m stressed”? What is it that’s stressing you? Just be with it for a moment. That’s observing — the O in STOP.

Then you get to P. What do you think P is? Process it. Just look at it, think about it. You might be feeling it. Let the stress be felt. Then you say: OK, what can I do about it? By processing it, you’re allowing this circuitry — this whole network, think of it however you want — to come alive, to make some new connections, and maybe to start to guide you to where you want to go. So: proceed towards your goal. What’s my goal here?

It’s very interesting what we hear from people. The goal was to get today done, and then get tomorrow done. But they start to notice, and through that stimulation they get to a metacognitive state. People have come back and said, “I’ve been noticing it so much, I think I need a change in my life.” That was not what your stress was telling you. But these connections start to come up — just as we hear from people in psychedelic trials — and you start to make connections at multiple levels.

First: yes, I’m stressed. I’m going to do this thing first, then that thing, maybe manage it another way, delegate something. Solutions start to come up. You’re now problem solving — actively coping — which wasn’t happening when you just had to get this done and that done and shove everything else out.

The final aspect is that other reflective, contemplative aspects of cognition start to tell you something, and you can do what you want with it. People start to do life-changing things; they start to think about growth in themselves. Now, that’s a process. I’m drawing it out in a short time to motivate you to engage with it — not to flood yourself, because that’s not what we want. Shoving and avoidance are very natural. It’s not bad, and there’s no judgement there. It’s natural for us to survive and cope. But remember that your body has still felt it and knows what happened, at some level, body and mind. Noticing it is going to get you back in control of it.

Audience member: [partly inaudible] … and others are like … So what would you say is a way for someone like me to expand their capacity?

Rajita Sinha: That’s a great question. Really start to engage. Start with STOP, notice it, and do things that bring down your anxiety, so you can notice the baseline coming back down — getting yourself back up and down. “I was anxious, but I came back down.” Exposure does a little of that: what is making you anxious? Your anxiety will go down, and then we do something to actually help you bring it down.

That’s not to say we don’t use avoidance in certain ways. There are times, with STOP, when I’ll have you experience it and then have you start to let go, or ask: can you move away from it mentally? So you give your body and mind the ability to let go, come back down and reconnect, to bring the baseline down. There’s a bit of work there, but those are great questions to explore for yourself.

Rajita Sinha: You had a question?

Audience Q&A: fascia, fads and the old-fashioned basics

Audience member: Last week I was at a talk from [inaudible] about the interstitium, and fascia. I’m very curious to get all of your takes on whether the fascia system is something real or more of a trend. There are some papers on connections to the limbic system, to chronic stress, and a lot on interoception as well. Is myofascial release something you work with or come across, or do you think it’s nonsense?

John Krakauer: One thing I think is really important — how should I put this? Modern life is a bit of a nightmare. Lots of people have written about this: people have lost a sense of mission, of communal goals. There is an epidemic of self-absorption. And what that leads to is a susceptibility to faddism. What’s the latest supplement? What’s the latest doodad I can wear on my head? Now we’ve got vagus nerve stimulation, with no evidence base, but everyone does it.

So, paradoxically, all this obsession with the latest thing is anxiety-provoking. The irony is that you’re making your anxiety worse in this hunt for the latest thing that’s going to help you. It’s like a horrible trick being played on you by the wellness industry.

The fact of the matter is that the things that work and have the best evidence are the old-fashioned, analogue, simple things. Sleep well, eat well, have friends, read books and exercise. All these other things, if you look at the amount of variance they explain, are minuscule. Minuscule.

But for some reason I don’t fully understand — because I don’t suffer from this affliction myself — we don’t want those old-fashioned things. We want new ideas. Maybe there’s something to them. I haven’t read all those papers, but my guess is that if I did, I would find them generally awful, and the amount of variance they explain is probably extremely low relative to the old-fashioned things.

The question you have to ask yourself is: why are we so obsessed with these new things? Is it to be hip, to be cool, to be in? Viewing this from the outside, I would strongly recommend that you be very, very, very sceptical — unless you’re happy dissolving into your own placebo effect, which maybe is OK, I don’t know. At the current moment, I think the old-fashioned things carry the day.

And we have to ask ourselves why we don’t want that. My guess is that practising for hours and hours to be a good dancer isn’t what we want. What we really want is something like Trinity in The Matrix: I want to be a helicopter pilot — whoop — I’m a helicopter pilot. We want everything to be like that. We want it to be quick. So even though we claim to be holistic, we’re actually just like the old-fashioned doctors: we want a prescription for something magical that will work fast. Despite all our progressiveness, we’re the same reductionists as the doctors we get annoyed by. I think you need to escape this paradox. That’s my recommendation.

Rajita Sinha: I’d add one more thing, just to clarify. The old-fashioned pieces are fabulous. I call them the goalposts for health and well-being. The one caveat is that when you’re stressed — as in your example, especially with chronic stress, but certainly in periods of stress — those goalposts get knocked down, very automatically. “I forgot to have breakfast this morning, and I’m always so good about my regular meals.” Or eating healthily, or sleep, which came up earlier, has already gone for a six. Now I’m tired and I’ve got to do something.

A lot of our stress symptoms in fact knock down those goalposts. It would be amazing if we didn’t live in the kind of crazy world we do. But stress will knock those things down, and that’s when you’re challenged. I think people look for other things because they know they somehow couldn’t get all those basics done. That’s my furthering of the explanation.

Another question for you: were you talking about a disease state like fibromyalgia, or something different?

Audience member: [inaudible] … small-scale research and …

Fibromyalgia and functional neurological disorders

Joe Guarnaccia: There is a disease state called fibromyalgia, which is kind of a bucket. A lot of physicians don’t really believe in it, or believe it’s more psychosomatic. But from my experience, not only with MS but with other neurological patients, it is a real entity in a subset of people. Of course we don’t really understand it. But again, I think there’s an underlying defect that some people carry that makes them more susceptible to these conditions. It cuts across socioeconomic class, and it can be associated with other things — a lot of MS patients seem to have a sort of fibromyalgia.

I just want to add one thing — I don’t know if you’ve encountered this. I’m sort of an old-timer, but in the last year I’ve become aware of this new neurological category called functional neurological disorder.

John Krakauer: Well — I don’t even know what that is. Yes, I do; you have to be very careful. Again, it’s the word. There’s a new kind of medicine, functional medicine, and I haven’t the slightest idea what it means. I think it’s, again, nothing.

But functional neurological disorders are real. They’re a very interesting phenomenon. I’ll give you an example of one of my functional patients. A patient came in paralysed down one side. We examined them, and it wasn’t consistent with a classic corticospinal tract hemiparesis. I demonstrated this to the medical students. But they were paralysed. They weren’t pretending, they weren’t acting, they weren’t malingering. They couldn’t move.

On further questioning, it turned out that a few months before, this patient had been driving one-handed and ran someone over. The stress of that event led to a functional paralysis on their right side.

Unidentified panellist: Is that different from a conversion disorder?

John Krakauer: Conversion is the mechanism, and the disorder is a functional neurological disorder. It’s fascinating. And there’s work now to see whether stress can induce an actual reversible lesion in the brain. This is weird stuff, but it’s real. It’s like the black spot in Treasure Island: you’re handed it, and you die. If you chase a rhinoceros and don’t dart it in time, it can suffer sudden necrotic cardiac death, because it’s so stressed by being chased that it dies from sympathetic overload.

So all these things are real: stress, the sympathetic nervous system, damage, functional neurological disorders. A third of movement disorders in neurology are functional. But that’s different from functional medicine, which, as I said — turn and run when you hear it. As far as I can tell, it’s regular medicine with a bit more sympathy and psychotherapy. But functional neurological disorder is real, and there’s a lot more mechanistic work into it now. A fascinating thing.

Audience Q&A: does practising many skills make you more adaptable?

Jeff Krone: We had one there.

Audience member: I’ve been involved in [inaudible]. A lot of movement training assumes that developing a broad repertoire of physical skills makes someone generally more adaptable — Bernstein, adaptable dexterity. But skills, when tested, show high specificity. So I’m wondering: if we practise a lot of different things, how much transfers across domains to make us more adaptable?

John Krakauer: There are so many deep things in that. It’s absolutely true that one of the fascinating things about practice is that it suffers from the curse of task specificity. We don’t really know why, but when you practise something, it doesn’t generalise as much as you’d think. The cognitive benefits of practising one thing, though, do generalise. In other words, it’s not that if you want to get cognitively better you have to practise twenty things. That’s not true.

“Adaptable” is another interesting word; it has two meanings. One is the generalisation question. Otherwise — there was an incredible article written about this. Has anyone watched the Mission: Impossible movies? This is a take-home message. If you notice the team Tom Cruise assembles around him, they’re all manually very skilled: a pickpocket, a bomb defuser. So the only way to defeat our digital overlords is to be manually or physically very skilled and adaptable. That’s actually the message of Mission: Impossible — watch it next time. The goodies are all analogue, skilled, good at something, kung fu or whatever. And the idiots being taken over by AI are just desk jockeys.

So there’s a lot to be said for being physically fit and multi-skilled, and maybe for general cognitive fitness. But I don’t think it follows that somebody who has practised eight things is better than someone who’s practised five, or worse than someone who’s practised twelve. Unless you want to win the decathlon.

Audience member: [partly inaudible] … the examples of the three different groups people were in …

John Krakauer: Wrestling, treadmill and brain games. Definitely wrestling is the most [inaudible]. Absolutely, no question. It’s a skill you have to think about, it’s cardiovascular, and it’s fun.

Audience Q&A: critical periods and addiction

Jeff Krone: You had a question over there — and there’s someone over there too. There are several questions. Max, how are we doing for time?

Max Rodman: Let’s do two more.

Jeff Krone: Two more. Go ahead.

Audience member: [partly inaudible] I had a question about the critical period. It sounds like it’s either a damage response, as in a stroke, or a response to dosing with psychedelics, or maybe it’s just exciting a certain pathway. Are these different critical periods? [inaudible] And the second is about addiction: people with different types of addiction involve different parts of the brain and different reasons for being addicted. You said you want to integrate different parts of the brain to build resilience. Is that relevant to every type of addiction, or would you do something different for, say, alcoholism, a depressant? [inaudible] Are you just tamping down the signal?

John Krakauer: We get to pick one, right? On the critical period one: that work is just beginning, and there may be multiple critical periods — social ones, motor ones. It’s a fascinating era. Psychedelics do seem to open the critical period, in certain cases.

Before we get to the other one, here’s another warning. There’s an enormous temptation to keep talking about the brain when you’re talking about psychological things. I would avoid that. Yes, we might find neural correlates. But there’s something called the mereological fallacy. The idea is: wings don’t fly; birds do. There’s no part of the brain that is itself depressed. You are.

So there’s a tendency to reify regions of the brain. People say dopamine is for reward — silly things like that — or that [heard as “prolactin”; likely “oxytocin”] is the love drug. No. There’s a tendency to take complex psychological states and read in popular books that it’s a brain region. It doesn’t actually explain anything to say a brain region is doing something, unless you have a theory established before you look.

So when it comes to psychological states — whether you’re stressed and anxious at work — yes, there may be ways you can be treated, through psychotherapy, through medications. But there’s a wonderful paper called “the strange, seductive allure of brain explanations for psychological states” [published title: “The Seductive Allure of Neuroscience Explanations”, Weisberg et al., 2008]. Yes, it’s a real paper. And I think it’s very important — unless you’re a neuroscientist specifically theorising — not to succumb to this seductive allure of putting brain words into sentences about psychological states, because most of the time it’s pseudo-explanation.

Rajita Sinha: So John and I will get into a bigger debate about that, because this is the border between neurology and psychiatry. We won’t go there — he’s baiting me. After all, what is psychology? Is there a mind separate from the brain? I’ll let John ponder that for a minute and we’ll argue later. I totally agree about the region part, but I won’t say that something is psychological and not the brain. So that’s where we are.

But to your second question, about all these different addictions. There are different brain regions, dare I say, or different characteristics of different addictions. But there is a common pathway. It has to do with what the word addiction means: you’re doing something over and over again, or spending lots of hours on it — a behaviour, a substance, whatever the addiction may be — especially at the cost of other things. That cost can show up in multiple ways. Other things don’t feel as rewarding. So there is a common path across specific addictions, which is why they get labelled addiction, and certain correlates of that have been shown, neurochemicals and other things.

Your question was whether you’d treat it differently — to recover from addiction, are you [inaudible]? Well, you’re learning something new, but you’re also breaking something. I will go down the road of rewiring, if I may: you’re really learning a different path, which takes time. This is where we also think about stimulating the different buckets of experience. Because, as I said about what addiction is, it becomes very channelled: one thing at the cost of the other things. When we look at whether you’re feeling your interoceptive states, those have gone numb. They’ve gone silent. So we want to bring them back up. That’s what we’d want to be doing.

Audience Q&A: PTSD

Jeff Krone: You have a different question — I think you’re allowed one.

Audience member: [largely inaudible; a question about PTSD] … What do you recommend for any of this? … experiencing PTSD and such high stress … maybe being more of an anxious person … maintaining habits can be [inaudible] … it’s complicated.

Rajita Sinha: What you’re highlighting is the saturated state, which is very much part of an active post-traumatic stress state. You could have chronic PTSD, or an acute post-traumatic stress arousal state, and that would be at this high saturation point. What I was talking about earlier applies: finding ways — and getting professional help is really important. What you described is that even exercise feels like a stressor and a burden, because you can’t take any more. So start there: recognise and notice that, and what you need to do to actually come back down, and see whether what we’ve talked about today matches your experience.

Audience member: But for the average person, a lot of people struggle with [complex?] PTSD. How do you address that? [inaudible] What’s an outlet, if it’s not psychedelics?

Rajita Sinha: To your point — and I know we have to stop soon — there are some great trials going on with psychedelics for PTSD, to start to open up the stimulation of the various buckets of experience, as I’ve been talking about, and also to bring the baseline down. One of the things I like to say is that with PTSD, it is literally four buckets all getting fired up, in a way, for resetting. I don’t mean stimulate all of them and go back into an oversaturated state. I mean you have to target all four. It’s a long conversation about how to get there, obviously, because it’s so prevalent.

Thank you for talking about it. You’re absolutely right: there is so much trauma in the world. We talk about this all the time. And we are doing what the earlier question was about — surviving. Putting it away, avoiding it, putting it in a bucket because I can’t deal with that stuff. And yet that comes at a very high cost. So it’s really important to acknowledge what you’re saying, and its importance.

Right now, today, we do not have a medication for PTSD. We do have behavioural strategies. We do have movement, which does seem to help. There are integrative therapeutics that are working and helping. We do better with acute than chronic, as you mentioned. So this is a huge problem, and we can talk more about specific strategies. But it’s really important to acknowledge it, and that people are at that stage and not able to live their best life.

Close

Max Rodman: Thank you so much. We’re going to close there. I’m so sorry if there are other questions, but there are teams that have to close the space and open it again in the morning. So thank you all for coming, and thank you all for your time.

[applause]