Speaker 1: What happens in the brain when we face adversity and
Speaker 1: why do two people with the same hardship walk away
Speaker 1: with such totally different outcomes. Is resilience something that you're
Speaker 1: born with or is it something your brain can develop?
Speaker 1: And if so, how, what does any of this have
Speaker 1: to do with the diving bell and the butterfly, or
Speaker 1: using magnetic fields to zap the brain or the less
Speaker 1: famous partner to the brain's reward system, or.
Speaker 2: What seemingly unrelated.
Speaker 1: Disorders in psychiatry all have in common. Welcome to Inner
Speaker 1: Cosmos with me David Eagleman. I'm a neuroscientist and an
Speaker 1: author at Stanford, and in these episodes we sail deeply
Speaker 1: into our three pound universe to understand why and how
Speaker 1: our lives look the way they do. Today's episode is
Speaker 1: about resilience. We all know someone who's been through hell
Speaker 1: and somehow comes out standing. Maybe you know a person
Speaker 1: undergoing chemotherapy who still manages to raise a family and
Speaker 1: be a good parent, or a refugee who rebuilds their
Speaker 1: life from nothing, or a friend who keeps going after
Speaker 1: losing her job. There's something about resilience going on here
Speaker 1: that's different from what a lot of other people would
Speaker 1: do in the same situation.
Speaker 2: We're thinking about.
Speaker 1: This one a young man who gets an early onset
Speaker 1: motor neuron disease and slowly ends up completely paralyzed in
Speaker 1: a wheelchair and eventually loses his ability to speak, but
Speaker 1: he keeps on plugging along and eventually ends up becoming
Speaker 1: one of the premire mathematical physicists in the world. This
Speaker 1: is the story of Stephen Hawking. How did he stay
Speaker 1: so resilient in the face of a slowly creeping disease
Speaker 1: that ate his body but didn't seem to slow him down?
Speaker 2: That kind of drive, that kind of adaptation.
Speaker 1: It raises the question what enables some people to keep
Speaker 1: going when everything falls apart? What is human resilience made of?
Speaker 1: In this episode, we're going to answer this question by
Speaker 1: diving into the brain. And I'm going to do so
Speaker 1: with my colleague and friend, Jonathan Downer, who's been on
Speaker 1: Inner Cosmos before, and he's one of the most compassionate
Speaker 1: and insightful thinkers that I know. He has an MD
Speaker 1: and specializes in psychiatry, and he also has a PhD
Speaker 1: in neuroscience, and he's become one of the world's experts
Speaker 1: in transcranial magnetic stimulation, which is a technique that we'll
Speaker 1: come back to in a minute now. Jonathan was on
Speaker 1: Inner Cosmos about a year ago to talk about depression,
Speaker 1: and that episode moved and inspired a huge number of people.
Speaker 1: So I've wanted to sit down with Jonathan again to
Speaker 1: zoom out the camera one notch to talk about an idea,
Speaker 1: change and focus the idea that clinical depression is actually
Speaker 1: one expression of a more fundamental issue, one that has
Speaker 1: accidentally surfaced as neuroscientists around the globe have performed hundreds
Speaker 1: and hundreds of individual studies and then looked at the
Speaker 1: emerging shape that all of these studies were pointing to.
Speaker 1: What we'll learn today is an issue that sets right
Speaker 1: at the center of our lives. So let's dive in
Speaker 1: with Jonathan Downer to understand it. So, Jonathan, we've all
Speaker 1: known people who are in very terrible circumstances in life,
Speaker 1: and yet they figure out a way to keep going.
Speaker 1: So we might by this says resilience, So tell us
Speaker 1: about resilience. Yeah, So it's a fascinating topic to get into.
Speaker 3: I think a good example to start us off by
Speaker 3: way of illustration. You and I in our textbook talked
Speaker 3: about the case of Jean Boubie, who was the author
Speaker 3: of The Diving Bell and the Butterfly. I really like
Speaker 3: his examples. He had an absolutely horrific situation in which
Speaker 3: this was a successful author and editor of the French
Speaker 3: fashion magazine a magazine, and he unfortunately suffered a tiny
Speaker 3: little stroke in his brain stem that left him with
Speaker 3: this syndrome called locked in syndrome. And for those who
Speaker 3: are hearing about that for the first time, it's a
Speaker 3: horrible syndrome where the output passages from your the output
Speaker 3: tracks from your brain down to the spinal cord, and
Speaker 3: the muscles are just severed by the stroke. So you're
Speaker 3: perfectly awake, you're perfectly conscious, you can feel sensations, but
Speaker 3: you can't send any signals out to your body, and
Speaker 3: there's no recovery. He was then bedridden and the only
Speaker 3: part of his body he could move where he could blink,
Speaker 3: and that was pretty much all he could do, and
Speaker 3: with the assistance of some of the people who work
Speaker 3: with him, he would use a blinking code to specify
Speaker 3: letter by letter what he wanted to say.
Speaker 1: Specifically, the assistant would read out the letters of the
Speaker 1: alphabet in order of their frequency, and then when she
Speaker 1: got to the right letter, he would blink his eye
Speaker 1: and she would write down that letter and then start
Speaker 1: the process over again.
Speaker 3: Yeah, and so the fact that he was even able to, like,
Speaker 3: I don't know what would happen to you or I
Speaker 3: or most of the people I know if they were
Speaker 3: in that situation.
Speaker 2: Certainly.
Speaker 3: I mean, imagine having an inch which you can't scratch
Speaker 3: because you can't move, or a pain in your leg,
Speaker 3: or a cramping your leg that you can't do anything
Speaker 3: about for hours. It's very hard to maintain a positive
Speaker 3: attitude in a situation like that. And yet he was
Speaker 3: able to laboriously blink out an entire book describing his experience,
Speaker 3: which the butterfly exactly. So, when I think about the
Speaker 3: fact that, to me, the most remarkable part about this
Speaker 3: is that is not the stroke or the fact that
Speaker 3: there's an assistant with this amazing blinking code. To me,
Speaker 3: the astonishing part is the fact that there's a there's
Speaker 3: a resilient spirit in there that's capable of doing that,
Speaker 3: that is laying there in this betting it somehow has
Speaker 3: the patience and the resilience and the I guess the
Speaker 3: inner fortitude to do something like that.
Speaker 2: So what is that about?
Speaker 3: So we I mean, there are a few different ways
Speaker 3: of looking at resilience that's been studied to death, and
Speaker 3: there are whole books that have been written on it.
Speaker 3: You can talk about psychological sources of resilience. You can
Speaker 3: talk about cultural practices and interventions and therapies that support it.
Speaker 3: You can talk about you know, social practices that support it.
Speaker 3: What I want to dive into a little bit is
Speaker 3: the actual neural circuitry behind it. Because we are learning
Speaker 3: a lot about what that neural circuitry is, and it
Speaker 3: turns out that there are indeed specific brain circuits which
Speaker 3: support our ability to be resilient. So, for example, a
Speaker 3: person who suffers a terrible stroke, if these circuits are
Speaker 3: preserved and the person can actually function a lot better
Speaker 3: than you would expect given the circumstances they're in. And
Speaker 3: then surprisingly, if those circuits are damaged in the stroke,
Speaker 3: the person may have minimal physical limitations and yet is
Speaker 3: not functioning at all. Is to sort of emotionally always
Speaker 3: getting stuck on things, cognitively always getting stuck on things,
Speaker 3: and just not able to get up and start moving.
Speaker 3: So I think what would be interesting to get into
Speaker 3: a little bit is the circuitry that we've been able
Speaker 3: to delineate behind the general ability to be resilient to
Speaker 3: life stresses and challenges and the general ability to function.
Speaker 1: And just before we get into the details of the circuitry,
Speaker 1: what is the variation in the circuitry across the population.
Speaker 2: Yeah, so that's fascinating.
Speaker 3: There's been a lot of studies done on that using
Speaker 3: techniques using MRI scans. So, for example, you can have
Speaker 3: a person going the scanner and you can actually map
Speaker 3: the thickness of their gray matter across the hole using
Speaker 3: a technique called boxel based morphometry. So they take all
Speaker 3: the little voxels in the scan and they look at
Speaker 3: how thick the grain matter is in different areas, and
Speaker 3: they can compare people who have more resilience versus less resilience.
Speaker 3: There was a famous study done, I guess about a
Speaker 3: decade ago now where they did exactly the question we're
Speaker 3: asking about. They took a whole bunch of people who
Speaker 3: had suffered horrible adverse childhood experiences. There's actually a psychological
Speaker 3: questionnaire called the adverse childhood experiences questionnaire. So all these people,
Speaker 3: you know, had been through horrible traumatic experiences, and yet
Speaker 3: a subset of them had never gone on to develop
Speaker 3: post traumatic stress disorder or depression or any other sort
Speaker 3: of classic you know, axis one mental disorder, and the
Speaker 3: question was, what's going on with them? It turns out
Speaker 3: that there were specific areas of the frontal lobes that
Speaker 3: had thicker gray matter. In these areas we were pinpointing
Speaker 3: specifically as an area we can get into called the
Speaker 3: left or salalateral prefrontal cortex, but it's actually a network
Speaker 3: of areas in the brain. Who seemed if you just had,
Speaker 3: by luck of the draw, you happen to have more
Speaker 3: gray matter in these areas, then you were more likely
Speaker 3: to be resilient to even quite horrible adverse childhood experiences.
Speaker 1: And is it luck of the draw a genetic issue
Speaker 1: or is it environmental practices or social practices.
Speaker 3: It's a really good point there are you know, the
Speaker 3: literature around resilience suggests that there's a lot to this,
Speaker 3: so you know, there is although there is some genetic
Speaker 3: component to resilience that I think that is greatly overshadowed
Speaker 3: by one's environment and one's psychology and one's upbringing and
Speaker 3: the practices that one implements. Early adverse childhood experiences are
Speaker 3: really bad for people's resilience, whereas growing up in a
Speaker 3: supportive childhood environment and having social supports and sort of
Speaker 3: a calm parenting environment and all the rest of it
Speaker 3: can often provide a person with quite a lot of
Speaker 3: resilience that they can tap into later on in life.
Speaker 1: Yeah, although there are you know, like everything it's a
Speaker 1: gene environment interaction. There are these studies done by Steven
Speaker 1: Swami with monkeys where he is looking at these monkey
Speaker 1: t and with half the adolescent monkeys he has them
Speaker 1: with their mothers and the other half he has them
Speaker 1: just with their peers. So they're raised with peers, and
Speaker 1: just like in junior higher high school, monkey peers are
Speaker 1: mean to one another. And so he looks at who
Speaker 1: ends up doing well and who doesn't, and it turns
Speaker 1: out it's not as obvious as you would think. It
Speaker 1: turns out that there are genetic predispositions that cause some
Speaker 1: of the monkeys in the bad group being raised with
Speaker 1: their peers to still do fine and others not. So
Speaker 1: there's definitely an interaction between how you're raised and what
Speaker 1: you come to the table with genetically.
Speaker 2: So let's jump.
Speaker 1: Into what you see when you're looking at this in
Speaker 1: the brain scanner. What are these prefrontal areas that you're
Speaker 1: talking about. So I think that might be a good
Speaker 1: place to start. So on the one hand, you know,
Speaker 1: let's say we have this technique called box based morphometry
Speaker 1: that's capable of pinpointing areas of gray matter they're thicker
Speaker 1: versus thinner in certain groups of people. And let's say
Speaker 1: we've used that to find people were unusually resilient to
Speaker 1: developing access one disorders despite adverse childhood experiences. The flip
Speaker 1: side of that would be looking at people who do
Speaker 1: have access one disorders and saying okay. And this was
Speaker 1: an enterprise that began, and I guess around twenty ten
Speaker 1: or so on. They started being able to gather up
Speaker 1: big data sets of lots of people who had succumbed
Speaker 1: to depression or bipolar disorder OCT substance use anxiety disorders PTSD.
Speaker 2: And this is what you mean by access one disorder,
Speaker 2: So access one disorder exactly.
Speaker 3: So the sort of the classic sort of psychiatric disorders
Speaker 3: DSM one is the Diagnostic and Statistical Manual, and so
Speaker 3: the access one of that is just one way of
Speaker 3: describing formal clinical psychiatric disorders. So this was a team
Speaker 3: led by a meet at Ken at Stanford University and
Speaker 3: Madaline Goodkind was the first author, And in twenty fifteen
Speaker 3: they gathered up over two hundred studies that had been done,
Speaker 3: or close to two hundred studies that have been done
Speaker 3: looking at the thickness of grain matter across all these
Speaker 3: different disorders, and they asked a really interesting question, are
Speaker 3: all the different disorders like OCD and PTSD are.
Speaker 2: They completely different?
Speaker 3: Do they all involve different brain circuits or is there
Speaker 3: some common element like if you did a bend diagram
Speaker 3: and overlaid them all. Is there some common element to
Speaker 3: all the brain disorders that we have lumped into the
Speaker 3: basket of psychiatric disorders as opposed to neurological disorders.
Speaker 1: And so amazing by the way that we can do
Speaker 1: this now because we have enough brain scans from enough
Speaker 1: patients with different disorders that for the first time in
Speaker 1: history we can ask that question.
Speaker 2: It was fair. Yeah, absolutely, So what do they find fascinating?
Speaker 3: So they turn out that yes, indeed, if you overlapped
Speaker 3: all the maps of all these two hundred different studies
Speaker 3: involving I think close to seven thousand patients versus healthy controls.
Speaker 3: There were indeed some areas which were universally thinned out
Speaker 3: across all these different disorders, and as you might expect,
Speaker 3: they belong to the same network that this resilient network was,
Speaker 3: except it was in the other direction. So people will
Speaker 3: then use with quite thick gray matter in this network
Speaker 3: of regions were resilient to disorder. And on the other hand,
Speaker 3: if you looked at people who had these disorders PTSD
Speaker 3: or anxiety, one common element they all had was that
Speaker 3: this specific network of regions was a little bit thinner
Speaker 3: in terms of the gray matter. There are a bunch
Speaker 3: of different networks in the brain that perform various functions.
Speaker 3: Some of them move your upper body or your lower body,
Speaker 3: or do vision or hearing. This particular network having an
Speaker 3: interesting name, it's called the salience network.
Speaker 2: And so what was need about this popped out?
Speaker 3: The common element across all these different disorders when people
Speaker 3: lose their resilience is the salience network. And on the
Speaker 3: other hand, if your salience network is intact, then you
Speaker 3: tend to have this resilience.
Speaker 1: So help us understand this a little bit more so,
Speaker 1: if you have less resilience, how does that connect with
Speaker 1: psychiatric disorders?
Speaker 3: So that's really I think that's a really great question
Speaker 3: and the right way of putting it. So the salience network,
Speaker 3: it helps understand what the salience nets works function seems
Speaker 3: to be. What was need about discovering that the salience
Speaker 3: network was involved is that separately, people had been studying
Speaker 3: the saliens network for fifteen years. I accidentally did my
Speaker 3: PhD audit back in the late nineteen nineties before we really.
Speaker 2: Knew what it was.
Speaker 3: But its job seems to be a thing called cognitive control,
Speaker 3: the ability to self regulate your thoughts and your behaviors
Speaker 3: and your emotions. What's unique about it in terms of
Speaker 3: the brain regions it involves is it has some brain
Speaker 3: reasons that are part of the limbic system, the so
Speaker 3: called emotional system the brain, but it also has some
Speaker 3: areas that are part of the brain's kind of executive
Speaker 3: function and cognitive system. So it's out of all the
Speaker 3: various dozens of brain networks that are there, it uniquely
Speaker 3: seems to break between the limbic system and the cognitive
Speaker 3: system between sort of reason and emotion, and you will
Speaker 3: see people activating it when they have to inhibit a
Speaker 3: particular thought in order to do or a prepotent response.
Speaker 3: So a classic example that would be the go No
Speaker 3: Go task, which is a task where people have a
Speaker 3: signal that tells inn apress button and then another signal
Speaker 3: says no, wait, don't do that, and so you have
Speaker 3: to inhibit that predisposition.
Speaker 1: So for example, if if the banana comes on the screen,
Speaker 1: I pound the button, and if the strawberry appears on
Speaker 1: the screen, I have to not hit the button.
Speaker 2: That's a great example, that'd be it.
Speaker 3: Another example would be the classic stroop task, which in
Speaker 3: the stroop task, this is a tricky one. If you
Speaker 3: ever have to try it, you can They have them
Speaker 3: online if you ever want to go and try them.
Speaker 3: With the word blue will be written in red ink
Speaker 3: or the word red will be written in green ink,
Speaker 3: and you have to not say the word, which is
Speaker 3: the thing you want to do, but you have to
Speaker 3: actually push past that prepotent response and say the color
Speaker 3: of the word, even though there's an interference effect there.
Speaker 3: So the stroop task and all these things volitionally activates
Speaker 3: your cognitive control capacity. It essentially allows you to stop
Speaker 3: ruminating to or and to focus on what kind of
Speaker 3: response you're going to make, so the salience network will
Speaker 3: kick in. If a person, I'll give you an example,
Speaker 3: if you, for example, got bored with what I was
Speaker 3: saying right now in your mind started to wander till
Speaker 3: yesterday or.
Speaker 2: Tomorrow or why.
Speaker 3: I usually say this lectures, and you know, it's a
Speaker 3: room full of people, so you know, you could always
Speaker 3: see the people like some people are paying attention to
Speaker 3: It's totally natural. It's very hard to focus your attention
Speaker 3: for a long time, so people start thinking about something
Speaker 3: else and then maybe suddenly I say something interesting and
Speaker 3: their attention comes back again. At that moment when you
Speaker 3: stop mind wandering and you return to the present moment,
Speaker 3: your salience networking is activating at that moment. For people
Speaker 3: who have done mindfulness meditation, we've all experienced this.
Speaker 2: You know, Okay, I'm going to be mindful.
Speaker 3: I'm going to pay attention to my breathing, and then
Speaker 3: after about you know, three seconds, your brain starts wandering
Speaker 3: off to something you have to do later that day
Speaker 3: or whatever. And then and you wander and wander and
Speaker 3: then after about a minute you're like, oh, I actually,
Speaker 3: I wasn't supposed to be doing that. I'm supposed to
Speaker 3: be paying attention to my breath, and at that moment
Speaker 3: of mindfulness you return. So at the moment of mindfulness
Speaker 3: being again, your salience network comes on as you break
Speaker 3: the train of thought. So we can imagine that as
Speaker 3: we go through life, we're often not in the present moment.
Speaker 3: We're ruminating about the past or the future or something else.
Speaker 3: But the moment that we snap out of it and
Speaker 3: return to the present moment the sailing this network seems
Speaker 3: to activate every time that happens. So you can imagine
Speaker 3: what would happen if the sailings network goes down. If
Speaker 3: you lose that capacity to easily snap out of things,
Speaker 3: then your ruminations will just keep going and keep going
Speaker 3: and keep going. And the minute that you can't snap
Speaker 3: out of things, all of a sudden, it's harder to function.
Speaker 2: Right.
Speaker 3: So, you know, all of us, if we're faced with
Speaker 3: a stressful situation, let's say we start worrying about it
Speaker 3: and thinking about something horrible that's happened, you know, if
Speaker 3: we lost someone important to us. But as long as
Speaker 3: we can snap out of that thought and return to
Speaker 3: our task or our work or whatever doing. We don't
Speaker 3: have an access one disorder. We have stress, we have distress,
Speaker 3: but we don't have disorder. But the day you can't
Speaker 3: snap out of it again is the day you flip
Speaker 3: over into having a disorder.
Speaker 1: So, with this understanding coming into focus, what kind of
Speaker 1: therapeutic approaches are there?
Speaker 2: Beautiful? So let's go to that.
Speaker 3: So let me also tie that back to resilience, because
Speaker 3: I'll say, resilience has a few different As we start
Speaker 3: to tease apart this circuitry, we start to realize that
Speaker 3: resilience has a few components to it. One of this
Speaker 3: isn't the only circuit behind resilience, but one of the
Speaker 3: circuits behind resilience is this salience network and its role
Speaker 3: of cognitive control and the ability to snap out of
Speaker 3: mind wandering and rumination. So that thing we call cognitive
Speaker 3: control or cognitive flexibility is one of the ingredients of resilience,
Speaker 3: and it is one that can be enhanced over time,
Speaker 3: as you say, one of the classic ways to enhance it.
Speaker 3: We know that, as I mentioned during Moments of Mindfulness,
Speaker 3: that the salience networks engage. So people who wish to
Speaker 3: enhance their resilience, mindfulness based stress reduction and mindfulness based
Speaker 3: cognitive therapy are tried and true sentxuries old, I mean
Speaker 3: thousands of years old methods that if you spend years
Speaker 3: and years practicing, you can strengthen one your capacity to
Speaker 3: be in the present moment or at least return to
Speaker 3: the present moment when you need to, and to maintain
Speaker 3: yourself there. When you're sitting there meditating for ten or
Speaker 3: twenty minutes, every time you catch yourself and bring yourself back.
Speaker 3: You can think about that as one rep. It's like
Speaker 3: one sit up of this system. And so the idea
Speaker 3: behind ten years of mindful at practices you're going to
Speaker 3: do a whole lot of situps and at the end
Speaker 3: that that system is going to be fairly strong.
Speaker 1: So we have mindfulness meditation is one way to practice this.
Speaker 1: How else are you thinking about this from the neurological point?
Speaker 3: Yeah, I think that's great. So there are Yeah, So
Speaker 3: that's exactly it. So that's one way of doing it.
Speaker 3: When people go for there are. Evidence based psychotherapy is
Speaker 3: like cognitive behavioral therapy, and that's a little bit different
Speaker 3: from mind welellss. You're not merely returning to be present
Speaker 3: with whatever feelings or thoughts are there. But the trick
Speaker 3: is when you get into a difficult situation and your
Speaker 3: emotional state goes out of control or your behavior goes
Speaker 3: out of control. In cognitive behavioral therapy, we teach ourselves
Speaker 3: to reframe situations or thoughts in a different way, so
Speaker 3: we're actually exerting cognive control to look at the situation
Speaker 3: a bit differently and figure out whether our emotions and
Speaker 3: our thoughts are proportionate to the situation or disproportionate, and
Speaker 3: then try and bring them back again. And that also
Speaker 3: involves activatingly at these regions. So those are tried and
Speaker 3: true methods that have been out there. I'm not aware
Speaker 3: of any specific medication that in a targeted way boost
Speaker 3: these things. So there are medications that help with the
Speaker 3: access one disorders, but I'm not aware of a medication
Speaker 3: that specifically does this one thing of enhancing one's cognitive control. Uh.
Speaker 3: You know, stimulants for some people and things like ADHD
Speaker 3: when they are is just a little underactive. There are
Speaker 3: certain groups of people who find that they gain contentitive
Speaker 3: control on you know, people with ADHD, for example, may
Speaker 3: find that medications enhance their ability to exercise or exert
Speaker 3: cognitive control.
Speaker 1: One of your errors expertise is transcriminal magnetic stimulation, So
Speaker 1: tell us about that.
Speaker 2: That's exactly where I was going.
Speaker 1: So first, for the benefit of the listenership, tell us
Speaker 1: what TMS is, and then tell us how it applies here.
Speaker 3: Perfect, Okay, So yes, So right now, we've got this
Speaker 3: target circuit in the brain that we'd really love to
Speaker 3: strengthen because if only we could strengthen it for people,
Speaker 3: they would have more cognitive control, and they'd have more
Speaker 3: resilience and so on. And medications don't do it for
Speaker 3: most people, but and therapy takes a really long time,
Speaker 3: and not everyone has the capacity to do it.
Speaker 2: But if we could.
Speaker 3: Somehow stimulate that area and turn it on over and
Speaker 3: over again, like do the sit ups for people, then
Speaker 3: you know, we could be able to strengthen it. And
Speaker 3: the method that we're using successfully to do that right
Speaker 3: now is called transcranial magnetic stimulation. TMS is the short form.
Speaker 3: It's a method for stimulating the brain non invasively. So
Speaker 3: in the old days, you want to stimulate the brain,
Speaker 3: you have to do surgery, open up the skull and
Speaker 3: implant use an electrode to stimulate the brain. Nowadays we
Speaker 3: can do that non invasively using a device that stimulates
Speaker 3: the brain through the skull using powerful focused magnetic field pulses.
Speaker 3: So a little inductor paddles placed over the target region
Speaker 3: of the brain and it'p little quick pulses. It's powerful
Speaker 3: enough that if you apply the little pulses to the
Speaker 3: area of your hand that moves your thumb, for example,
Speaker 3: you'll actually see the person's thumb move. And I think
Speaker 3: you and I have gone through that as a little demonstration,
Speaker 3: and it was discovered back in the nineteen ninety is
Speaker 3: that if you do this not once or twice, but
Speaker 3: if you do this hundreds of times, you can strengthen
Speaker 3: the circuits that you're stimulating via the mechanisms of neuroplasticity,
Speaker 3: which of course you've discussed elsewhere at length. The neurons
Speaker 3: that you fire together will gradually wire together. So when
Speaker 3: you deliver tms to any area of the brain, not
Speaker 3: only do you activate that area, but the other areas
Speaker 3: it's connected to will also light up, and they all
Speaker 3: fire together, and they all wire together. So you can
Speaker 3: sort of do hundreds of sit ups for a person
Speaker 3: in about three minutes of TMS using these sequences of pulses.
Speaker 3: It's been known for a long time dorsal that TMS
Speaker 3: two regions like the dorsalateral proof on cortex and so on.
Speaker 3: Back in nineteen ninety five, it was first demonstrated that
Speaker 3: this can be useful in treating depression, and then it
Speaker 3: turned out to be useful in treating other things like
Speaker 3: anxiety and other targets turned out to be useful in
Speaker 3: OCD and PTSD and binge eating disorder and bolivia orvosa
Speaker 3: and lots of other conditions. Interestingly, when we look back
Speaker 3: at what areas we'd been stimulating back in the nineties
Speaker 3: and later on, it turned out that a lot of
Speaker 3: the areas we were activating with TMS corresponded very nicely
Speaker 3: to this network, this alience network, which had been active
Speaker 3: across many different disorders. For those of us in the field,
Speaker 3: that solved the mystery where we come in and say, look,
Speaker 3: I thought we were just trying to treat the page.
Speaker 3: And when I opened my TMS clinic in twenty ten,
Speaker 3: we kept seeing this. We'd have a person who came
Speaker 3: from the eating disorders clinic. Oh, well, but you know
Speaker 3: you're depressed, so let's see if we can help you.
Speaker 3: So we treat the depression and they come back in
Speaker 3: and they say, well, Doc, you didn't tell me my
Speaker 3: Bolivia was going to go away. And they said, wow,
Speaker 3: that's interesting. How do you think about that? And then
Speaker 3: you'd have a person who came in for depression, but
Speaker 3: their bigger picture they were a veteran with PTSD and
Speaker 3: they come and say, you know, I'm not having flashbacks anymore.
Speaker 3: I can walk into Walmart now without having panic attacks,
Speaker 3: Like my anxiety is way down. You'd have other people
Speaker 3: who'd walk in and say, you know, I took a
Speaker 3: mindfulness course once and I just couldn't do it, but
Speaker 3: I noticed after the TMS, now I can do mindfulness,
Speaker 3: or say I took a therapy course once and I
Speaker 3: tried to learn how to do CBT and I tried
Speaker 3: the techniques and you know, I really I tried for
Speaker 3: two years. I was like teaching it to my roommate
Speaker 3: and she could do it, but I couldn't do it.
Speaker 3: But now after the TMS, I can do it now,
Speaker 3: like it actually works now. So there's a synergy between
Speaker 3: these areas of brain and our ability to stimulate them
Speaker 3: with TMS. And what we've noticed as we stimulate these
Speaker 3: areas is is it turned out to be very hard
Speaker 3: to just treat the person's depression or just treat their PTSD.
Speaker 2: If it kicked in and worked, a lot of things
Speaker 2: got better.
Speaker 3: And it was really fascinating what they would come in
Speaker 3: and you would ask them, Okay, well, okay, I see
Speaker 3: the numbers on your scale are down, but just tell me,
Speaker 3: in your own words, what's different now, And they say,
Speaker 3: you know, it's really weird.
Speaker 2: You know.
Speaker 3: Traditionally, I'm constantly ruminating about my body image all day,
Speaker 3: Like I can't stop thinking about my weight, I can't
Speaker 3: think about the way I look. And then I noticed that,
Speaker 3: you know, I had a and then someone said, someone
Speaker 3: made a comment, my aunt made a comment about my appearance.
Speaker 3: And normally that would have ruined my entire day, and
Speaker 3: I would have been still ruminating about it when I
Speaker 3: went to bed, and it was really weird. I noticed
Speaker 3: an hour later that I just wasn't thinking about it.
Speaker 3: I was kind of over it. I was thinking about
Speaker 3: other things again. And so these are the kind of
Speaker 3: things people would keep on talking about that some challenge
Speaker 3: would come along and what they were used to over
Speaker 3: years of having the disorders.
Speaker 2: Not a challenger come along. Okay, that's my week gone.
Speaker 3: I'm going to be stuck ruminating about this for the
Speaker 3: rest of the week.
Speaker 2: I won't be able to do anything.
Speaker 3: And what they kept noticing was saying, yeah, I get upset,
Speaker 3: and then twenty minutes later, I'm over it. And I said, well,
Speaker 3: is that a weird experience? You feel like you're being
Speaker 3: emotionally numbed or emotionally blunted.
Speaker 2: No.
Speaker 3: No, I still have my emotions, but I can get
Speaker 3: over things now and I don't overreact as much as
Speaker 3: I used to. My reaction is like sort of, you know,
Speaker 3: more proportionate. And I find I can and say, what's
Speaker 3: the experience like? And they use words like willpower and control?
Speaker 3: They say, I feel more like I'm in control again.
Speaker 3: I feel like I have that willpower thing that everyone's
Speaker 3: been telling me. I need more of that. Their subjective
Speaker 3: experience of having this network strengthen is an experience of
Speaker 3: greater willpower, greater control.
Speaker 1: And so does it matter which part of the network
Speaker 1: was stimulated or were these many different studies stimulating various
Speaker 1: different parts, but it all happened to be of this network.
Speaker 3: Well, so it's been a long time piecing that together
Speaker 3: because in the TMS literature, different people targeted. Some people
Speaker 3: will do the left hemispheres, someone do the right hemisphere,
Speaker 3: someone go in the middle between between the two hemispheres,
Speaker 3: and so on. And now that we've got enough of
Speaker 3: these studies and we put them together, it looks like
Speaker 3: you kind of get fairly similar results no matter which
Speaker 3: as long as it's one of the members of this
Speaker 3: network of regions, all the other networks are lighting up
Speaker 3: as well, And so it seems to have a similar
Speaker 3: effect when we scan people while we do TMS. You
Speaker 3: see that when you're stimulating one area, all the other
Speaker 3: areas and its network will light up.
Speaker 2: And how effective is this approach?
Speaker 1: Is it ninety percent of patients get better in some
Speaker 1: way as it ten percent?
Speaker 3: So that's been that remembering the TMS is a technology.
Speaker 3: So if you asked me the question in nineteen ninety five,
Speaker 3: it would be asking a little bit like how far
Speaker 3: can your electric car drive in nineteen ninety five versus
Speaker 3: how far can your electric car drive in twenty twenty five.
Speaker 2: There's the good. Dow says, there's progress.
Speaker 3: The early TMS studies were only getting about ten or
Speaker 3: fifteen percent of people their emission, but they were also
Speaker 3: only doing about ten or fifteen sessions of treatment. And
Speaker 3: then later studies did about thirty sessions of treatment and
Speaker 3: got about thirty percent of people better. And then later
Speaker 3: studies did about fifty sessions of treatment and sometimes you
Speaker 3: get fifty percent of people better. And then other studies
Speaker 3: were using MRI guidance to kind of fine tune the
Speaker 3: location of the stimulation, and it turns out some people,
Speaker 3: it turns out there because of their anatomy, you need
Speaker 3: to have map their anatomy a little more closely to
Speaker 3: get the coil over the right spot. But the biggest breakthrough,
Speaker 3: I think in the last two or three years is
Speaker 3: noticing that TMS require, as we mentioned, it requires the
Speaker 3: brain to have neuroplasticity. Right. There are implantable brain stimulators
Speaker 3: that people use for Parkinson's and depression and so on,
Speaker 3: and then a surgeon will implant them like a little
Speaker 3: pacemaker in the target circuit and then you walk around
Speaker 3: with it all day long. TMS isn't like that you
Speaker 3: sit in the chair, you get a session a treatment
Speaker 3: for three minutes, and after a bunch of sessions you
Speaker 3: then it has to keep lasting for weeks or months,
Speaker 3: even after you've gotten the treatment done. So the only
Speaker 3: way that that works is if you have neuroplasticity, and
Speaker 3: some people just don't have very much. We don't know why,
Speaker 3: but there's a lot of variation. So when we treat
Speaker 3: a bunch of people with depression, about twenty percent of
Speaker 3: people show really strong and really rapid response, and then
Speaker 3: about ten percent of people show nothing at all, and
Speaker 3: everyone else is somewhere in the middle.
Speaker 2: It's almost like you're bailing.
Speaker 3: A bit of a leaky boat, so you're kind of
Speaker 3: bailing it out, but they're getting worse, and then they
Speaker 3: tend to keep coming back. These are the ones who
Speaker 3: seem to need more plasticity. And one of the ways
Speaker 3: that has just come out in the last two orths
Speaker 3: years to make TMS a lot better is it turns
Speaker 3: out that there are some simple, off the shelf old
Speaker 3: medications that enhance the brain's plasticity, and if you take
Speaker 3: those medications a little like an hour or so before
Speaker 3: you get your TMS sessions, it works a lot better,
Speaker 3: and it lasts a lot longer.
Speaker 1: Give us a sense of what some of these meds are,
Speaker 1: just in case the name strikes that any was familiar.
Speaker 2: Happy to do it, so there is.
Speaker 3: So my colleague Alex McGear at the University of Calgary
Speaker 3: back in twenty twenty two publish a paper in Gemo
Speaker 3: Psychiatry using an old it's actually an old anti tuberculosis
Speaker 3: medication called de cyclosarine. Decyclo Sarine works on the brain's
Speaker 3: glutamate system. If we want to get really nerdy, it
Speaker 3: acts on the NMDA receptor. The NMDA receptor is the
Speaker 3: receptor that detects whether two neurons are being fired at
Speaker 3: the same time and then responds to that by strengthening
Speaker 3: the connection between them. So you need your NMDA receptors
Speaker 3: to do that whole plasticity thing where the neurons that
Speaker 3: fire together wire together. So what happens if you add
Speaker 3: a medication that tickles the NMDA receptor and kind of
Speaker 3: helps it stay open a little bit longer and then
Speaker 3: do the tms. Decycoserian has been around since the fifties
Speaker 3: and psychiatrists have been using it and medical researchers have
Speaker 3: been using it not for tuberculosis, but to try and
Speaker 3: enhance plasticity while they give therapy and give other kinds
Speaker 3: of treatments exposure therapy and phobias and OCD and so on,
Speaker 3: And I think one of my colleagues described the results
Speaker 3: as myth after many many years, the result was sort
Speaker 3: of some But interestingly, it might just be that those
Speaker 3: kind of therapies don't provide the direct kind of potent
Speaker 3: immediate stimulation of the neural connections the way that TMS does.
Speaker 3: Because the first time this was tried for TMS, the
Speaker 3: effect was not small. It doubled the remission rate, and
Speaker 3: that was just giving it for the first ten out
Speaker 3: of twenty sessions of TMS. You know, instead of the
Speaker 3: twenty percent remission rate you might expect with twenty sessions,
Speaker 3: it went up to forty percent. And then actually just
Speaker 3: two months ago Alex mcgerr's team went back and they
Speaker 3: tried it again for all twenty sessions and the remission
Speaker 3: rate went from twenty percent to seventy percent, eighty five
Speaker 3: percent of people showing at least. So it turns out
Speaker 3: there are a lot of people who just need more
Speaker 3: plasticity to do well on TMS, and TMS actually can
Speaker 3: be extremely powerful if you just enhance the plasticity first.
Speaker 3: So that was and then of course this is just
Speaker 3: about depression. So he also went to a different brain
Speaker 3: area that was involved in OCD. Because there is a
Speaker 3: TMS protocol for OCD, OCD is a tough nut to
Speaker 3: crack among TMS researchers. We think of it obsessed with
Speaker 3: compulsive disorders reckoned to be one of the toughest things,
Speaker 3: just for when they do clinical studies on OCD, they
Speaker 3: will often declare thirty five percent improvement in symptoms as
Speaker 3: a strong response, and they if you like, we don't
Speaker 3: expect to cure you of your OCD. If we can
Speaker 3: even get your thirty five percent better, we'll call that
Speaker 3: a win. That's often how structure studies are done. Alex
Speaker 3: mcgear's team when they did this in OCD, they found
Speaker 3: that twenty sessions. Uh, there's a school or there's a
Speaker 3: scale from zero to forty called the Yale Brown Obsessive
Speaker 3: Compulsive Score. It's the standard clinical scale you used to
Speaker 3: measure how bad somebody's OCD is. And you know you'll
Speaker 3: have a person who might have a score of twenty
Speaker 3: six which would be severe, or thirty which would be
Speaker 3: very severe, and twenty sessions of TMS would reduce their
Speaker 3: score by about two or three points, but with decyclicerine
Speaker 3: it was closer to ten points of reduction in twenty sessions.
Speaker 2: Great, so it's a big difference.
Speaker 3: And you know, the question is, well, okay, TMS is
Speaker 3: used for lots of other things, like TMS is being
Speaker 3: used for other brain circuits and Parkinson's and Alzheimer's, so
Speaker 3: could this be used to treat lots of things. There's
Speaker 3: a second wave of enhancing plasticity, which is dopamine. So
Speaker 3: dopamine has a lot of roles in the brain, but
Speaker 3: it does look like TMS relies upon dopamine for at
Speaker 3: least some of the plasticity. And there have been studies
Speaker 3: done in both in laboratory and in the real world
Speaker 3: in which if you give people medications that boost their
Speaker 3: dopamine levels, like el dopa for example, Parkinson's drug that
Speaker 3: adds dopamine to the brain, and then you do the
Speaker 3: TMS the excited where ATMs protocols get stronger, the effect
Speaker 3: of the TMS gets stronger, so you're boosting plasticity.
Speaker 2: So it looks like.
Speaker 3: There's at least two or three different receptor and neurotransmitter
Speaker 3: systems that.
Speaker 2: Can be used to do this. How about a seedyl colin.
Speaker 2: That's an interesting one.
Speaker 3: So that hasn't been try yet, but you know there
Speaker 3: are easily four or five or six different methods for
Speaker 3: doing this. I don't know if you've had Lee Williams
Speaker 3: come in and talks of Lee Williams here at Stanford
Speaker 3: has been looking at it at guanphisine, not necessarily on
Speaker 3: a cell colin, but looking at guanfessine to see what
Speaker 3: that's a third neurotransmitter system involving neuropinephrin, and has been
Speaker 3: showing that people with problem there are specific people with
Speaker 3: depression who stand out for having particularly prominent difficulties with
Speaker 3: cognitive control. And here's a medication called guafisene that isn't
Speaker 3: normally used as an antidepressant, but in these patients, they
Speaker 3: who happen to have what they call the cognitive control
Speaker 3: that fense. This medication does work as an antidepressant for
Speaker 3: these folks, probably by enhancing their cognitive control so they
Speaker 3: don't get stuck in rumination all the time.
Speaker 1: Right, Yeah, you know, this is such an exciting moment
Speaker 1: in time. We're in neuroscience where everybody has been doing
Speaker 1: these studies and we well know that to get a
Speaker 1: patient and do a study and so on a ton
Speaker 1: of work to do one patient, two patients, and suddenly
Speaker 1: we can do these meta analyzes and put together the
Speaker 1: big picture and start seeing the jigsaw puzzle more broadly.
Speaker 1: So what our next steps. We're almost halfway through twenty
Speaker 1: twenty five. Now where is this all going?
Speaker 3: Absolutely so, first of all, one of the there are
Speaker 3: two directions that the field is going in right now.
Speaker 3: One of them, which I think is a broader trend
Speaker 3: in psychiatry in general, is the field of personalized medicine.
Speaker 3: So let's look at your symptoms and let's see if
Speaker 3: we can achieve a higher chance of success by looking
Speaker 3: at your specific symptoms and personalizing maybe the frequency of
Speaker 3: treatment or the type of medication we use, or the
Speaker 3: location of the coil based on your specific parameters. Which
Speaker 3: is great if it works, but the downside of courses,
Speaker 3: it also has a lot more complexity. So you know,
Speaker 3: psychiatric treatments are already costly and hard to get, and
Speaker 3: so this makes them more costly and more hard to
Speaker 3: get the other potential approach that we could try not
Speaker 3: to say that then there's certainly going to be a
Speaker 3: role for that. Personalized medicine is certainly looking very exciting.
Speaker 3: But there are some things there's a different approach where
Speaker 3: we try not to personalize and when we simply try
Speaker 3: to come up with the sort of greatest good for
Speaker 3: the greatest number approach. And so I want to unpack
Speaker 3: that a little bits to point at the idea that
Speaker 3: there might be some brain story. I mentioned earlier, there
Speaker 3: are some brain circuits that are universally involved across a
Speaker 3: variety of different disorders. And so one of the questions
Speaker 3: I asked one of my colleagues at Harvard who have
Speaker 3: been doing one of these brain mapping type studies and seeing,
Speaker 3: instead of mapping the circuits that are associated with depression
Speaker 3: or PTSD or addictions or whatever, we notice that some
Speaker 3: people just have resilience, so they actually function much better
Speaker 3: than expected. For those of us whore working clinics and
Speaker 3: see thousands of patients, you'll see these people who have
Speaker 3: like terrible depression and yet somehow like they're still functioning
Speaker 3: really well. Or people who have terrible Parkinsons and can
Speaker 3: barely move, and somehow they're still kind of functioning or
Speaker 3: you know, have had a stroke that's crippling to them,
Speaker 3: and as we mentioned earlier, somehow still functioning and then
Speaker 3: functioning mentally and in the activities of daily life, like yes,
Speaker 3: they're super you know, there's somehow still. I actually saw
Speaker 3: a gentleman, what was it, I don't know whose name.
Speaker 3: We were having brunction pol Walta just up the road
Speaker 3: and there was a little man, it looked in his
Speaker 3: nineties in a wheelchair by himself, and he was out
Speaker 3: for a while. He was using one leg and his
Speaker 3: heel to drag his wheelchair along one foot at a time,
Speaker 3: and he smiled and waved to us, and he kind
Speaker 3: of crept along sidewalk for his morning stroll. And he
Speaker 3: was and I don't know who got him into the
Speaker 3: chair or how he's getting along, but there he was,
Speaker 3: just using one foot to drag himself around the block
Speaker 3: for a little morning scroll. And so we can evaluate
Speaker 3: how severe your symptoms are, but we can independently evaluate
Speaker 3: how well you're functioning in daily life. So that gentlemen
Speaker 3: I mentioned would be an example of someone who if
Speaker 3: you measured their physical symptoms, they would be totally crippled.
Speaker 2: But if you actually they're still.
Speaker 3: Getting up every morning and walking around and having breakfast
Speaker 3: and doing all their stuff, So on that level, they're
Speaker 3: better than expected. So the question becomes, let's run an
Speaker 3: analysis of strokes or lesions or other things and figure
Speaker 3: out are there areas that correlate with your better than
Speaker 3: expected or worse than expected number if we think of that,
Speaker 3: But and they do, they pop out and one of
Speaker 3: the two There are two circuits that popped out of
Speaker 3: that analysis, which was led by Beatrice Milano and with
Speaker 3: my colleague Shan Sidiki and his group over at Harvard.
Speaker 3: They went through a whole bunch of stroke patients and
Speaker 3: they looked at their ability to function in general. And
Speaker 3: the circuits that popped out. Number one involved this one
Speaker 3: of these salients network circuits that I talked about. But
Speaker 3: there was a second circuit that was down just above
Speaker 3: the eye in another circuit we haven't gotten to yet,
Speaker 3: called the orbit of frontal cortex, and it was also involved,
Speaker 3: but in the opposite polarity. In other words, it was
Speaker 3: actually good to have lesions in this area. And if
Speaker 3: this area was preserved you were more likely to be
Speaker 3: functionally impaired. How do we understand that? So that's an
Speaker 3: interesting one because this circuit is also pretty well studied
Speaker 3: and it is the counterpart to the brain's so called
Speaker 3: reward circuit. So the brain most of us know, has
Speaker 3: this sort of a reward circuit whose job it is
Speaker 3: to identify goals that are worth pursuing and to motivate
Speaker 3: us to go and pursue those goals. The problem is
Speaker 3: that that would only allow us to pursue positive goals.
Speaker 3: We also need a partner circuit to identify potential pitfalls
Speaker 3: or problems, challenges, threats, and to establish goals to avoid
Speaker 3: those things and motivate ourselves to avoid those. If you
Speaker 3: don't have both circuits, you're in trouble. The brain needs
Speaker 3: to be motivated to seek out stuff, but also needs
Speaker 3: to be motivated to avoid the bad stuff. And the
Speaker 3: circuit that was overactive in these stroke patients, or so
Speaker 3: to speak, or was the one that was the so
Speaker 3: called non reward circuit, whose job it was to be
Speaker 3: motivated to essentially to generate negative motivations.
Speaker 1: It looks like, so you said that was overactive in
Speaker 1: the stroke patients is that there's a specific thing we
Speaker 1: think is happening in that circuit, it can enter into
Speaker 1: a feedback loop, right.
Speaker 3: And this is a theory by a professor in the
Speaker 3: UK called Professor Edmund Rules. He'd been studying the orbit
Speaker 3: of frontal cortex region in monkeys and humans for decades
Speaker 3: and he after many years, realized that this circuit tended
Speaker 3: to get stuck in a feedback loop in depression, and
Speaker 3: he proposed what I think is a very lovely theory
Speaker 3: called the non reward attractor theory of depression. So, in
Speaker 3: the non reward attractor theory of depression, you have a
Speaker 3: circuit whose job it is, to what it's functioning properly,
Speaker 3: is to identify threats, so you can then start to
Speaker 3: think about solutions and go and solve them. But if
Speaker 3: it gets stuck in a feedback loop, then you can't
Speaker 3: stop thinking about it even when you're not solving it.
Speaker 3: I think all of us have experienced the sensation at
Speaker 3: times of the difference between you know, working on a
Speaker 3: problem versus just worrying about a problem where you're not
Speaker 3: really solving it, but you're awake at two in the
Speaker 3: morning years thinking about the same thing over and over
Speaker 3: and over again, and you're not really getting anywhere, but
Speaker 3: you just keep going and keep going, and you can't
Speaker 3: get back to sleep, and you really just need to
Speaker 3: stop thinking about it because you're not going to solve
Speaker 3: it right now, and snap out of it and go
Speaker 3: back to sleep now if you can't. And if that
Speaker 3: goes on all day long, you're not functioning because you're
Speaker 3: sitting there ruminating and going round and around on problems.
Speaker 3: Maybe it's a one out of ten problem that your
Speaker 3: brain is treating as a ten out of ten problem.
Speaker 3: Maybe it's a three out of ten problem that your
Speaker 3: brain should be spending five minutes on and spending eight
Speaker 3: hours on. But the point is that while it's doing that,
Speaker 3: you're not getting up, you're not having breakfast, you're not functioning,
Speaker 3: you're not going to work, you're not really you're not
Speaker 3: fully present, you're not doing things.
Speaker 2: I'll give you an example of this.
Speaker 3: There was a woman described in the literature who is she,
Speaker 3: among other things, had she had sought treatment for many
Speaker 3: years for alcohol dependence. So she was somebody who drank
Speaker 3: about ten drinks a day and somehow functioned through this
Speaker 3: recently well. But was drinking ten drinks a day, and
Speaker 3: it sought treatment from physicians for this in a variety
Speaker 3: of different ways.
Speaker 2: Not a boich. You have been successful.
Speaker 3: In her fiftyes, she suffered a stroke and the strength
Speaker 3: was the stroke happened to land. It was a small stroke,
Speaker 3: just in this little circuit, and she immediately found it
Speaker 3: that she no longer had any desire or interest in
Speaker 3: consuming alcohol, and the alcohol, the use that she'd been.
Speaker 2: Trying to get her over for years just kind of
Speaker 2: went away.
Speaker 3: Other people with strokes in these areas, there are people
Speaker 3: who have obsessed with compulsive disorder and have suffered this
Speaker 3: is a weird thing that they had OCD for thirty
Speaker 3: or forty years, and then one day they have a
Speaker 3: stroke in their old age and the OCD goes away.
Speaker 3: So yeah, So there are situations where this circuit gets
Speaker 3: stuck in a feedback loop and the best thing you
Speaker 3: can do here function is to just get out of
Speaker 3: the feedback loop. Now, losing the circuit altogether is pretty drastic, right,
Speaker 3: That's what we'd rather do is just turn it down
Speaker 3: a little bit, and TMS can be used to do that.
Speaker 3: Back in around twenty sixteen seventeen, I had a patient
Speaker 3: who had come for TMS, and we tried the standard
Speaker 3: TMS of one of these salience network cress and we
Speaker 3: didn't get anywhere. So then we tried another salience network
Speaker 3: cretion and for reasons you know and I've described, that
Speaker 3: didn't do much either. And then she said, well, please,
Speaker 3: I please try something else because I you know, the
Speaker 3: next step normally would have been to go to electroconvulsive
Speaker 3: therapy or shock therapy, and she really didn't want to
Speaker 3: do that. So I said, well, there is this other
Speaker 3: area that's been tried in OCD, and you don't have OCD,
Speaker 3: but you do have a kind of depression that reminds
Speaker 3: us of OCD because you just kind of get obsessed
Speaker 3: with the same negative things about yourself. And when you
Speaker 3: described me what your depression is like, it sounds almost
Speaker 3: like an ocd ish flavor of depression. So if you will,
Speaker 3: like you can come in and I'll give you this
Speaker 3: treatment which has been used for OCD, and we'll say,
Speaker 3: maybe let's see if your OCD ish depression gets somewhere.
Speaker 3: And it was a complete remission. We also had scans
Speaker 3: on her and we were able to show that normally
Speaker 3: when we do TMS, we strengthen this salience network, and
Speaker 3: you can see this connection strengthened.
Speaker 2: In her case.
Speaker 3: We scanned her before and after, and when she got better,
Speaker 3: it had nothing to do with the salience network. Instead,
Speaker 3: we had suppressed the over connection between this orbit of
Speaker 3: frontal region and its little loop of activity down into
Speaker 3: the reward circuitry.
Speaker 2: So what happened to her after was what was what
Speaker 2: was it like for her?
Speaker 3: What she said was that essentially she was now free
Speaker 3: of ruminations. I'll give you, and we had other people
Speaker 3: come and do it, So I'll give you a really
Speaker 3: illustrative example of one person who had a little bit
Speaker 3: of both. She had a bit of column AN and
Speaker 3: a bit of COLUMNB. So not only did she have
Speaker 3: a tendency to be really obsessive and self critical and ruminative,
Speaker 3: but she also tended to be quite impulsive and a
Speaker 3: bit ADHD like and had difficulty with the cognitive control.
Speaker 2: So she really struggled.
Speaker 3: And she came to us from the eating sort of program,
Speaker 3: and she bring she had blimior nervosa, so she would
Speaker 3: spend a couple of hours a day binge eating and
Speaker 3: then purshing it up and binge eating, and pershing. She
Speaker 3: also had a lot of intrusive thoughts about her body
Speaker 3: image and negative body thoughts. She had PTSD symptoms. She
Speaker 3: had a lot of different things. So we gave her
Speaker 3: the standard TMS and her depression scores went down by
Speaker 3: about half, and she said, well, this is really interesting,
Speaker 3: Like I feel somewhat better, like I noticed, like I'm
Speaker 3: feeling less anxious and less depressed. And you certainly helped
Speaker 3: me with my bolimia because I haven't had any urges
Speaker 3: to beings or pursed, like those impulses are just gone.
Speaker 3: But I still think about suicide every day, and I
Speaker 3: still think about how horrible my body looks every day,
Speaker 3: and I can't enjoy anything. And so we talked about
Speaker 3: it a bit. And when I heard about these obsessions,
Speaker 3: I said, well, you know, we could try going to
Speaker 3: this other area that's typically an OCD area and see
Speaker 3: if these obsessive thoughts you have about body image and
Speaker 3: suicide and so on, let's see what that does. Because
Speaker 3: a couple of other patients have been helped by it.
Speaker 3: It was a while before we could get her in.
Speaker 3: The clinic had a lineup, so we treated her and
Speaker 3: then she came back in. This was lovely about She
Speaker 3: came in and I asked her how she was doing,
Speaker 3: and her scores down to the single dishits she was
Speaker 3: doing really, really well. And I asked her, but what
Speaker 3: was it like? And she said, well, I'll tell you
Speaker 3: what I noticed. It was this past weekend. I was
Speaker 3: playing with my niece and nephew, and I noticed that
Speaker 3: I was smiling, and I noticed I was feeling pleasure,
Speaker 3: like joy, which is weird. I hadn't felt that in
Speaker 3: twenty years. And then I thought about it, and I
Speaker 3: realized I actually hadn't thought about suicide all day, and
Speaker 3: that hasn't happened for twenty And I realized I hadn't
Speaker 3: thought about suicide for days, which hasn't happened.
Speaker 2: I was able to enjoy things.
Speaker 3: And then I realized I'd eaten a hamburger four days ago,
Speaker 3: and normally i'd still be thinking about that.
Speaker 2: Hamburger, regret about you, regret exactly.
Speaker 3: I'd still be thinking like, why did you do that you?
Speaker 3: And I realized that I just wasn't worried about the burger.
Speaker 3: I'd eaten it, and yeah, I was a little upset
Speaker 3: about it, but then I just wasn't thinking about it anymore.
Speaker 3: But this was three or four months after her original treatment.
Speaker 3: She said, but could I come back and have the
Speaker 3: previous one again, because I'm starting to get back into
Speaker 3: my binging and pershing behavior. That's that part is coming
Speaker 3: back again. So you can see it what we would
Speaker 3: in neuropsychology, a double dissociation, where treatment of one circuit
Speaker 3: is helping with the person's impulses and their cognitive control.
Speaker 3: And after treatment there she felt a stronger sense of
Speaker 3: agency of self control with this first set of areas
Speaker 3: around this alience network.
Speaker 2: With the second set of.
Speaker 3: Areas, she was feeling freedom from being trapped in a
Speaker 3: circle of rumination on negative thoughts. But as the first
Speaker 3: one wore off, she was losing that control piece. And
Speaker 3: that highlights the two elements of resilience that come from this.
Speaker 3: That what the ingredients of resilience seed be these two circuits.
Speaker 3: Number one, having more self control or agency or a
Speaker 3: sense of will to snap out of things or control
Speaker 3: what you're thinking about. And number two, the ability to
Speaker 3: not get stuck in a circle of rumination on the
Speaker 3: same stuff, the ability to exit that circle. If you
Speaker 3: have those two things, you're resilient.
Speaker 1: So cut to a quarter century from now when this
Speaker 1: is all very well worked out and every shopping mall
Speaker 1: has a TMS clinic that you can walk into and.
Speaker 2: I hope are there soon.
Speaker 1: Yeah, Okay, The question is how will people know whether
Speaker 1: they should go in and get this stream. It's like
Speaker 1: it's like doing a tune up on your car. But
Speaker 1: how do you know, you know, is there some variety
Speaker 1: that would be useful to have in our society. How
Speaker 1: do you know when you should get it at what level?
Speaker 3: Yeah, it's a really interesting question, particularly because TMS is
Speaker 3: a technology, so it gets better, it gets faster, it
Speaker 3: gets cheaper over time. So you know, it's the example
Speaker 3: of you know, when I was a kid, we talked
Speaker 3: about flying to like space tourists who would go up
Speaker 3: to flying space hotels, and that hasn't happened yet because
Speaker 3: the cost of flying a space would have to come
Speaker 3: down a lot before most of us can afford to
Speaker 3: do that. And likewise, TMS presently is still pretty expensive.
Speaker 3: But you know, the costs are coming down and the
Speaker 3: availability is going up, and so the threshold for and
Speaker 3: TMS happens to have an excellent safety profile, So the
Speaker 3: question would become of when to go and get TMS.
Speaker 3: Right now, it is an FDA cleared technique, and it
Speaker 3: is the FDA is the cleared to be a prescription treatment,
Speaker 3: so one one does go to a physician and obtain
Speaker 3: a prescription to get TMS.
Speaker 2: And in the.
Speaker 3: Past, most insurers and pairs would require people to have
Speaker 3: tried three or four or five or six different medications
Speaker 3: before they often four medications or more before they were
Speaker 3: allowed to apply for coverage for TMS. Now those numbers
Speaker 3: are coming down and people are able to go earlier on.
Speaker 3: So I think what we'll see is that it may
Speaker 3: be that you'll be able to go for TMS to
Speaker 3: enhance your functional capacity. Just knowing that we have these
Speaker 3: two target circuits, people will be able to go in and.
Speaker 2: Across a wide variety of disorders.
Speaker 3: So at the moment, TMS is FDA cleared in depression,
Speaker 3: it's FDA cleared in OCD, and in chronic pain a
Speaker 3: couple of other conditions. But what might happen is it
Speaker 3: might be cleared across a wide basket of different conditions.
Speaker 3: And because the TMS really isn't what's interesting is we
Speaker 3: discovered the TMS isn't treating the depression.
Speaker 2: It's indirectly treating that by just.
Speaker 3: Generally enhancing your self control and allowing you to not
Speaker 3: get stuck in rumination. And that turns out to be
Speaker 3: useful not just for depression, but for lots of things.
Speaker 3: So where I hope we end up in hopefully a
Speaker 3: lot less than twenty five years, maybe in five years,
Speaker 3: would be in a situation where people can come in
Speaker 3: across a wide variety of conditions and maybe not waiting
Speaker 3: until they're extremely severe and until they've tried lots of
Speaker 3: other things. But you know, there may even be a
Speaker 3: world where you know, even and this is one thing
Speaker 3: people are working on, is even before going to medications,
Speaker 3: where people might be able to go and pursue this
Speaker 3: treatment right away. As you know, So when a person
Speaker 3: first starts to realize that they're encountering significant difficulty functioning
Speaker 3: because of the severity of their anxiety or depression or
Speaker 3: whatever it be, that they can go in and get
Speaker 3: essentially a top up of resilience.
Speaker 2: The thing that we all wish we had.
Speaker 3: That comes back to a dinner conversation we had ten
Speaker 3: years ago where I was sitting with some friends and
Speaker 3: as a dinner conversation starter, we said, okay, let's go
Speaker 3: around the room and let's say you had the abilit
Speaker 3: to just rub a magic lamp and a genie would
Speaker 3: would you could say one word and then everyone in
Speaker 3: the world would.
Speaker 2: Be gifted that thing. So what would you?
Speaker 3: And we all went around the table, and the one
Speaker 3: I chose was happened to be resilience. I said, the
Speaker 3: world would just run better if we could all have
Speaker 3: a little bit more resilience. So I would love to
Speaker 3: get to a world where we just generally have this
Speaker 3: treatment that enhances one's ability to be resilient, And if
Speaker 3: we could get that out to everybody with you know,
Speaker 3: a relatively short.
Speaker 2: Treatment, not that we shouldn't.
Speaker 3: Also, you know, people can go and do mindfulness and
Speaker 3: cognitive therapy and all these other things, and that.
Speaker 2: That takes time and skill set.
Speaker 3: It's it's like piano lessons, You've got to put putting
Speaker 3: your time and your hours to do it. But I
Speaker 3: think those piano lessons will go faster for people if
Speaker 3: we can use if we can drop on their inner strengths.
Speaker 3: Let's pull out your maximum because we all have these
Speaker 3: circuits and we all have neuroplasticity. So every human being
Speaker 3: has every human beings brain, as you've discussed many times,
Speaker 3: has the ability to rewire and change itself, and every
Speaker 3: human being has somewhere in though theo's circuits that allow
Speaker 3: us to do cognitive control and to escape from rumination
Speaker 3: and so on. These are all innercapacities that are hit
Speaker 3: that are within all of us, and some of them
Speaker 3: it's on the surface the highly resilient people, but in
Speaker 3: people who aren't feeling resilient, where people do have these
Speaker 3: access one disorders, it's not that they don't have that capacity,
Speaker 3: it's just it's latent, it's hiding, and we're now having
Speaker 3: a capacity by combining targeted brain stimulation with neuroplasticity enhancement,
Speaker 3: we can bring out the person's inner strengths. And I
Speaker 3: think that's something that is just would be I wish
Speaker 3: if we could have everybody listening to is just no
Speaker 3: one thing, is that all of us have these inner
Speaker 3: strengths inside us, and some of us has been hidden
Speaker 3: en dormant for a long time. But I think every
Speaker 3: one of us those abilities are there and we can
Speaker 3: bring them to the surface.
Speaker 1: That's beautiful. Let me just ask one last question I
Speaker 1: wanted to come back on, which is the influence of
Speaker 1: our social lives on resilience.
Speaker 3: That's beautiful and I'm really glad you brought that up,
Speaker 3: because up until now, everything we've been talking about with
Speaker 3: resilience is are like are like. The human atom he's
Speaker 3: just started for individuals in isolation is one human brain
Speaker 3: just by itself, a bunch of circuits inside a skull.
Speaker 3: But we don't live as little atoms. No, no human
Speaker 3: as an island.
Speaker 2: We all have.
Speaker 3: We live within a broad social fabric. And I think
Speaker 3: you can delve into any number of beautify written books
Speaker 3: on resilience, we'll talk about one of the greatest and
Speaker 3: most important things supporting a person's resilience is the social
Speaker 3: supports and fabric that they have around them. Most challenges
Speaker 3: can be faced if they're not faced alone.
Speaker 2: I think most of it.
Speaker 3: I talked to a colleague of mind, and he talked
Speaker 3: about how his favorite part of medical training was actually
Speaker 3: in medical school, which some people see is the toughest part.
Speaker 3: So but the thing is, I had these two buddies,
Speaker 3: and the three of us we did all our studying together.
Speaker 3: We worked through it was all we were these comrades,
Speaker 3: and we felt like when we faced the world, we
Speaker 3: were unstoppable. Like you know, it's a very stressful thing
Speaker 3: going through training in medical school, but as long as
Speaker 3: I have my two buddies with me, we could face anything. Yeah,
Speaker 3: and I think a lot of us have that experience.
Speaker 3: So there's been is, you know, a tremendous amount of
Speaker 3: research done on the importance of social fabric and social
Speaker 3: supports and a strong social network.
Speaker 1: Well, what would you recommend for people? What do you
Speaker 1: recommend for people in terms of building a social life.
Speaker 2: Well, it's I mean, it's tricky.
Speaker 3: I think there's certainly been a shift over the last
Speaker 3: decade in terms of, you know, how people spend their time,
Speaker 3: and if everybody else is just locked away on, you know,
Speaker 3: in solitary activities of one type or another, then it's
Speaker 3: harder and harder to go out there and find people
Speaker 3: to do social things with. But I find that the
Speaker 3: way people build social communities is often either through mutual
Speaker 3: connections or through mutual activities. So you can meet friends
Speaker 3: through other friends, and you can and so friends are
Speaker 3: good at introducing other friends, and activities are also good
Speaker 3: at introducing and connecting people.
Speaker 2: Together.
Speaker 3: So one way you can kind of get two birds
Speaker 3: of one stone is you know, running clubs have become
Speaker 3: incredibly popular, just to take one random example of ways
Speaker 3: that people have decided to sort of quit dating apps
Speaker 3: and instead of just go out and go on these
Speaker 3: big running clubs. And this is how young singles are
Speaker 3: kind of meeting each other is by finding some kind
Speaker 3: of activity in common. But whether you fall into that
Speaker 3: category or not, I think there are I think a
Speaker 3: variety of different websites and so on out there, like
Speaker 3: meetup dot com is an old one that's been around forever.
Speaker 3: I thought it was quite clever, the idea that you
Speaker 3: just have various activities and people could connect over an
Speaker 3: activity or an interest that they had in common. So
Speaker 3: I think whether it's reaching out to a faith community
Speaker 3: if you're somebody who follows a particular faith, or whether
Speaker 3: it's an interest group, or whether it's a physical activity
Speaker 3: like exercise or running, I think finding activities to connect
Speaker 3: with other people who have that common interest is a
Speaker 3: really really great way of strengthening your connections with other people.
Speaker 2: Finding common purpose among cultures.
Speaker 3: It's interesting if you go read up on the culture
Speaker 3: of Okinawa Okinawa's for various is identify as one of
Speaker 3: these blue zones where people live unusually long and so on.
Speaker 3: But one of the interesting things that they talk about
Speaker 3: is the unusual psychological resilience of people in Okinawa and
Speaker 3: the concept of which I was introduced to recently. I'm
Speaker 3: probably going to say it wrong, but eke guy is
Speaker 3: a there's a word, eke guy. I'm probably going to
Speaker 3: butcher this, but as I understand it, it is the
Speaker 3: idea of having a purpose or a calling or a
Speaker 3: cause and part of the culture there is that you know.
Speaker 3: And it could be something incredibly small, it's like literally
Speaker 3: like breaking a beach and keeping it tidy, or it
Speaker 3: could be or it could be something lars like trying
Speaker 3: to save the world from a resilience deficit.
Speaker 2: It could be anything whatsoever.
Speaker 3: But the idea that part of resilience involves in making
Speaker 3: sure that your life is imbued with meaning and that
Speaker 3: you have some kind of compass or some kind of
Speaker 3: guidance to it. And so I think if you can
Speaker 3: find that activity that you choose with the people around
Speaker 3: you to be a meaningful activity, something you find that
Speaker 3: gives you purpose and meaning in life, that carries eke guy.
Speaker 3: And if on top of that it's not just a
Speaker 3: personal meaning, but if you can then use that as
Speaker 3: a nucleus to build a community of other people around
Speaker 3: that common purpose, there incredibly resilience to be had and
Speaker 3: being a member of a community of other people, all
Speaker 3: of whom are dedicated to a common and meaningful cause.
Speaker 3: And I think if you don't have access to a
Speaker 3: TMS machine, I think that's certainly the compass that I
Speaker 3: would lean into.
Speaker 1: That was my conversation with Jonathan Downer. So what is resilience.
Speaker 1: We've long thought about it as a psychological trait. We
Speaker 1: talked about grit or determination or optimism. But what today's
Speaker 1: conversation hopefully makes clear is that resilience has a physical
Speaker 1: footprint in the brain. It's not just about what you
Speaker 1: choose to think. It's about how your networks are operating.
Speaker 1: It involves a carefully orchestrated interplay between brain areas involved
Speaker 1: in emotion and reward and control and so on. And
Speaker 1: these brain networks can dip the balance between breaking down
Speaker 1: and bouncing back. And I think this is some of
Speaker 1: the most exciting and practical work happening in neuroscience. People
Speaker 1: are identifying these circuits and they are influencing them using
Speaker 1: tools like PMS, and this can, when it works, enhance
Speaker 1: a person's ability to function across a whole spectrum of disorders.
Speaker 1: And so one lesson that emerges is that resilience isn't
Speaker 1: just something we summon after disaster strikes. It's something we
Speaker 1: can build ahead of time. It's something we can cultivate
Speaker 1: in the brain like a form of mental infrastructure, one
Speaker 1: that helps us face whatever is coming down the pike next.
Speaker 1: And as our knowledge improves and the technology improves, this
Speaker 1: all may eventually lead to a paradigm shift in mental health.
Speaker 1: Instead of treating one disorder at a time, like depression
Speaker 1: or anxiety PTSD, what if we focused upstream, What if
Speaker 1: we try to increase resilience itself across the board. Of course,
Speaker 1: biology is only part of the story. Social support, culture,
Speaker 1: personal meaning. These are all powerful factors and addressable factors
Speaker 1: when we're thinking about resilience in our lives. But it's
Speaker 1: amazing to realize that even in the hardest moments, the
Speaker 1: exact state of the networks in your brain matters for
Speaker 1: the degree to which you can be an active participant
Speaker 1: in recovery. Maybe if we come to understand resilience in
Speaker 1: the brain and psychologically and socially, we can help more
Speaker 1: people to thrive. So thanks for tuning in today. If
Speaker 1: this episode moved you or challenged you, or sparked questions,
Speaker 1: I'd love to hear from you. Pop me an email
Speaker 1: at podcast at eagleman dot com and if you ask
Speaker 1: me to, I can pass your note on to Jonathan
Speaker 1: as well. And if this episode made you think about
Speaker 1: someone in your life who embodies resilience, please share this
Speaker 1: episode with them. Science is catching up to something that
Speaker 1: people have known in their bones for a long time.
Speaker 1: The mind can bend without breaking, and sometimes in that
Speaker 1: bending it gets stronger. So until next time, take care
Speaker 1: of your brain so you can take care of each other.
Speaker 1: Go to Eagleman dot com slash podcast for more information
Speaker 1: and to find further reading, and check out and subscribe
Speaker 1: to Inner Cosmos on YouTube for videos of each episode
Speaker 1: and to leave comments. Until next time, I'm David Eagleman
Speaker 1: and this is Inner Cosmos.