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Speaker 1: What is depression and why are brains so easily able

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Speaker 1: to slip into it? Is depression detectable in animals? And

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Speaker 1: when we look across the animal kingdom do we see

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Speaker 1: options beyond fight or flight? And what does any of

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Speaker 1: this have to do with measuring depression medications in city

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Speaker 1: water supplies, or reward pathways in the brain, or the

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Speaker 1: prevalence of tuberculosis or zapping the head with magnetic stimulation.

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Speaker 1: Welcome to Inner Cosmos.

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Speaker 2: With me David Eagleman.

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Speaker 1: I'm a neuroscientist and an author at Stanford and in

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Speaker 1: these episodes we sail deeply into our three pound universe

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Speaker 1: to understand why and how our lives look the way

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Speaker 1: they do. Today's episode is about depression. We are going

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Speaker 1: to dive into the science behind it and we'll see

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Speaker 1: what new solutions are.

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Speaker 2: On the horizon. So let me start by assuming way out.

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Speaker 1: What fascinates me is not just what the brain can

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Speaker 1: accomplish in terms of our normal functioning, but also one

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Speaker 1: can't help but notice the fragility of the brain. I mean,

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Speaker 1: just think about how easy it is to lose.

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Speaker 2: Consciousness when you hit your head.

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Speaker 1: Or think about what happens when you drink alcohol and

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Speaker 1: your perception and your decision making changes, or you don't

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Speaker 1: get enough sleep, and how you behave and how you

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Speaker 1: decide these can become a little different. Or when you're

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Speaker 1: angry and you act differently, or if you consume psychedelic

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Speaker 1: drugs and your conscious experience changes entirely. What all this

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Speaker 1: tells us, I think, is that it's very easy for

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Speaker 1: the system to get knocked off its normal pathway. And

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Speaker 1: what's clear is that the brain puts an enormous amount

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Speaker 1: of effort into trying to stay operating in the normal range. Now,

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Speaker 1: given this context, one area that's fascinating and of massive

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Speaker 1: social importance is depression. This is a mood disorder. It

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Speaker 1: affects how you feel, how you think, how you handle

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Speaker 1: your daily tasks, how you eat and sleep. People with

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Speaker 1: depression feel persistently sad. They often feel empty or anxious, pessimistic, hopeless, worthless, helpless,

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Speaker 1: and they lose interest in the things that used to

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Speaker 1: bring them joy. They're slowed down in all the aspects

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Speaker 1: of their life, and often there are thoughts of suicide. Now,

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Speaker 1: almost everyone has had someone in their life who has

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Speaker 1: suffered depression at some point, whether that's recognized or not.

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Speaker 1: And generally everyone's first intuition when they have a friend

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Speaker 1: or a loved one who becomes depressed is to talk

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Speaker 1: them out of it, to say, hey, things are okay,

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Speaker 1: snap out of it, look at the bright side. And

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Speaker 1: eventually you might be tempted to say, come on, just

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Speaker 1: tough en up.

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Speaker 2: But the important lesson.

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Speaker 1: From centuries of psychiatry and more recently neuroscience is that

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Speaker 1: it's not so easy. It's a physical problem. And that's

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Speaker 1: why we talk about mental illness nowadays exactly as we

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Speaker 1: talk about a physical illness like COVID or a broken leg,

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Speaker 1: and that understanding opens the door to different approaches, because

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Speaker 1: a physical problem invites physical solutions. Now, my father was

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Speaker 1: a psychiatrist, and he was always impressed that he could

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Speaker 1: have a patient who would be suffering from clinical depression

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Speaker 1: and would lose his job and maybe lose his spouse,

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Speaker 1: and my father can make a prescription like let's say prozac,

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Speaker 1: and that patient often could get out of bed again

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Speaker 1: and then get his job back and win his spouse back. Now,

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Speaker 1: how do we understand this, Well, it's an issue that

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Speaker 1: I talk about a lot, which is that we are

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Speaker 1: made up of small pieces and parts, And the thing

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Speaker 1: to appreciate is that you are the sum total of

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Speaker 1: all those pieces and parts.

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Speaker 2: Whatever is going on.

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Speaker 1: At this microscopic level is you and your mood and

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Speaker 1: your behavior. Now, why would anybody think that crazy statement

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Speaker 1: is true. Well, there are many things that we see

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Speaker 1: in the clinics every day which teach us this lesson.

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Speaker 1: People can get damage to their brains and they can

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Speaker 1: no longer understand how to use a mirror, or they

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Speaker 1: can no longer name furry animals, or they can no

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Speaker 1: longer see colors, or understand speech, or understand music or

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Speaker 1: any We have a million other things that we think

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Speaker 1: should just come for free in the world. Now, what

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Speaker 1: this exposes is that these are functions of the brain,

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Speaker 1: and even if a little bit of the brain is damaged,

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Speaker 1: then you can't perform that function anymore.

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Speaker 2: Now, many of the sorts.

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Speaker 1: Of brain damage that you'll read about in an exciting

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Speaker 1: book about the brain, these are things that most people

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Speaker 1: won't see in their lifetimes. They won't know any friend

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Speaker 1: or relative who has these issues because they are rare

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Speaker 1: things to happen, and they usually involve damage to a

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Speaker 1: region of the brain from a tumor or a stroke

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Speaker 1: or a traumatic brain injury, and those things represent big

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Speaker 1: changes in the city of the brain, like an entire

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Speaker 1: block of New York City falling in an earthquake. But

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Speaker 1: there are much more subtle things that happen in the

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Speaker 1: brain as well, and these are changes that have to

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Speaker 1: do with the way the system runs, with its tens

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Speaker 1: of billions of neurons and trillions of synaptic connections. So

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Speaker 1: to return to the city analogy, imagine that instead of

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Speaker 1: big damage that you can see, the city still looks

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Speaker 1: the same, but parts of it are operating very subtly differently.

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Speaker 1: So the playwrights have all quit, and the city planners

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Speaker 1: have stopped planning, and the coffee shops are closing two

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Speaker 1: hours earlier, and all of this stuff impedes the city's

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Speaker 1: ability to thrive and be an active, well functioning place

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Speaker 1: for innovation and tourism. But it's all very subtle, and

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Speaker 1: if you looked at this from a drone flying over

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Speaker 1: the city, you really wouldn't see much of a difference.

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Speaker 1: It's small stuff that's happening at a small level, but

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Speaker 1: it changes.

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Speaker 2: The way that the city operates.

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Speaker 1: And again, who you are and how you see, the

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Speaker 1: world comes from the way that the city of your

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Speaker 1: brain is operating. In other words, the sum total of

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Speaker 1: what's happening under the hood your biology. And I think

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Speaker 1: the reason this is surprising is because we tend to

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Speaker 1: think of ourselves as being removed from our biology. You

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Speaker 1: are separate from it or able to ride above it.

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Speaker 1: So if you've ever known someone with depression, or had

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Speaker 1: depression yourself, you will know that you can't just say hey,

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Speaker 1: come on, cheer up, snap out of it. That doesn't

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Speaker 1: suffice to change the biology. And one of the most

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Speaker 1: pervasive and societally important examples of these kind of subtle

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Speaker 1: changes to the brain is with depression.

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Speaker 2: And so for this episode, I decided.

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Speaker 1: To call my colleague Jonathan Downer, who is an incredibly

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Speaker 1: insightful and empathic observer.

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Speaker 2: Of the brain.

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Speaker 1: He has an MD and specializes in psychiatry, and he

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Speaker 1: also has a PhD in neuroscience, and one of his

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Speaker 1: areas of expertise is depression. And as it turns out,

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Speaker 1: Jonathan and I wrote a textbook together on cognitive neuroscience

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Speaker 1: called Brain and Behavior, and this is the textbook used

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Speaker 1: at Stanford and at universities worldwide. And the textbook covers

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Speaker 1: a lot of ground, but for today, I just want

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Speaker 1: to zoom in on depression. So I rang him up

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Speaker 1: to get his perspective on this issue that is not

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Speaker 1: only neuroscientifically important and fascinating, but also, unlike the strange

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Speaker 1: deficits that you might see only in a textbook, you

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Speaker 1: almost certainly know someone with depression, perhaps someone close to you,

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Speaker 1: or perhaps yourself. It's a shockingly common challenge. So let's

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Speaker 1: dive in to understand it. So, Jonathan, how did you

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Speaker 1: get interested in studying depression?

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Speaker 3: Well, it's a bit of an interesting story, David. You'd

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Speaker 3: have to go back about years to when I was

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Speaker 3: a graduate student over at the Toronto Western Hospital. That

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Speaker 3: is a hospital that has a i guess a major

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Speaker 3: neurosurgical unit where they perform surgeries where they implant deep

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Speaker 3: brain stimulators, which are a bit like brain pacemakers, into

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Speaker 3: the brains of people with Parkinson's disease and other kinds

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Speaker 3: of neurological disorders. And in around two thousand and two,

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Speaker 3: a patient came in who was a middle aged woman

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Speaker 3: who had previously suffered from depression but no longer. She

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Speaker 3: was coming in to have the deep brain stimulators and

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Speaker 3: planted for her Parkinson's disease. They implanted the electrodes, one

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Speaker 3: on one side and one on the other, and during

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Speaker 3: the surgery they turned them on to make sure that

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Speaker 3: they are succeeding in reducing the person's hand tremors or

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Speaker 3: the other tremors in their body that they're trying to

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Speaker 3: have treated. What was interesting is when they turned on

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Speaker 3: the one on one side, the opposite hands started to

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Speaker 3: reduce in its tremor and the tremor went away, which

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Speaker 3: is exactly what they expected to happen. On the other side,

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Speaker 3: there was something very strange happened as soon as they

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Speaker 3: turned it on. Nothing high into her tremor whatsoever, and

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Speaker 3: instead she descended instantly into a deep despairing re experiencing

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Speaker 3: of her depression. It kicked him within seconds, and she

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Speaker 3: described it as a deep down, bad feeling in the

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Speaker 3: pit of my stomach. I wanted to cry, but I couldn't.

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Speaker 3: Someone could have come in to shoot me and I

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Speaker 3: wouldn't have cared. I couldn't have cared less. No, immediately

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Speaker 3: they turned the switch off again, and surprisingly, within seconds,

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Speaker 3: the sadness lifted again and they found themselves in a

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Speaker 3: very weird situation where every time they turned on this current,

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Speaker 3: the person would descend immediately within a few seconds into sadness,

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Speaker 3: and then every time they turned it off she would

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Speaker 3: be able to emerge within a few seconds. Again. It

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Speaker 3: was literally sadness at the flip of the switch.

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Speaker 2: Wow.

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Speaker 1: And so that's what's got you started in researching that.

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Speaker 2: So that's exactly it.

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Speaker 3: So at the time I was doing my PhD using

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Speaker 3: a technology called functional functional MRI, which I'm sure you've

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Speaker 3: talked about on the podcast before, which is a way

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Speaker 3: of using MRI scanners to look at the brain activity

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Speaker 3: of people as various things happen. So the neuros versions

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Speaker 3: wanted to understand what was going on, So we went

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Speaker 3: down to where the functional MRIs were being done and

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Speaker 3: they turned on and off one of the switches on

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Speaker 3: the one side that affected the tremor, and they were

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Speaker 3: able to show a particular brain pathway that was affected

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Speaker 3: controlling the motor circuits of the brain, which was the

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Speaker 3: intended effect. On the other hemisphere, though the electrode was

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Speaker 3: just a few millimeters off and as a result, it

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Speaker 3: had landed on some other pathways that projected out to

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Speaker 3: a completely different part of the frontal lobes, and every

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Speaker 3: time they turned on and off this part of the

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Speaker 3: frontal lobes, the person would instantly going out of the sadness.

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Speaker 3: Now that was happy news of the patient because they

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Speaker 3: were able to reposition the electrodes so that both electrodes

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Speaker 3: did the appropriate thing. But it got us thinking about

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Speaker 3: what this really meant about depression. All these theories at

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Speaker 3: the time that depression might be a chemical imbalance or

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Speaker 3: this or that, we really saw very directly that there

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Speaker 3: was a question of the activity of the brain and

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Speaker 3: that within seconds, one pattern of activity the brain led

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Speaker 3: to sadness, and within seconds, if that pattern of activity

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Speaker 3: could somehow be turned off, then the person's sadness would

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Speaker 3: go away. And that really got us thinking about whether

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Speaker 3: we might start being able to use things like brain

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Speaker 3: stimulation to understand what depression was about in the brain,

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Speaker 3: and maybe even to come up with a new generation

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Speaker 3: of treatments that work better than the medications and therapy

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Speaker 3: of the time.

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Speaker 2: Okay, terrific, So we'll talk about that.

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Speaker 1: Let's start with can you define depression clinical depression?

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Speaker 3: Sure? So, there are standardized definitions of depression that involve

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Speaker 3: a series of symptoms, the core of which is sad

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Speaker 3: or depressed mood most of the day most days, and

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Speaker 3: the second of which is a thing called anhedonia, which

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Speaker 3: is the inability to enjoy things or experience pleasure, a

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Speaker 3: loss of motivation, a loss of joy, a loss of

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Speaker 3: the brain's reward functions. In addition to that, there are

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Speaker 3: some standard symptoms that go along with that. Commonly, people

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Speaker 3: will have disturbances in their sleep or appetite, trouble with concentration,

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Speaker 3: They may have difficulty with their energy and fatigue levels,

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Speaker 3: and there are thoughts that come up long of self

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Speaker 3: harm and suicide that there are obviously the most concerning

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Speaker 3: parts about the depression. So that's the standard sort of

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Speaker 3: diagnostic approach by which we determine whether somebody has been

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Speaker 3: entering into a period of depression. It's unfortunately, really common.

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Speaker 3: At any given time in North America, about five percent

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Speaker 3: of people are in the middle of a depressive episode,

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Speaker 3: and at least ten percent of people, perhaps more these days,

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Speaker 3: are going to go through an episode of depression at

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Speaker 3: some point in their lifetimes. Almost everybody will have somebody

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Speaker 3: they know who has been through depression or is going

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Speaker 3: through depression or will go through depression.

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Speaker 1: So one of the things I want to talk about

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Speaker 1: is why this happens, What it is about the wiring

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Speaker 1: of the human brain that allows us to slip so

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Speaker 1: easily into that mode.

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Speaker 2: What are your thoughts on that.

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Speaker 3: It's a really fascinating question, And I think to answer that,

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Speaker 3: what we found is you can get a lot of

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Speaker 3: the clue to that looking at evolution or a biology,

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Speaker 3: because humans are not, by no means the only animals

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Speaker 3: that can go into it a spare like syndrome, I

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Speaker 3: mean depression. Most of us who have pets, and most

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Speaker 3: of us of animals who have seen situations where animals

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Speaker 3: can drop into a despair and stop eating and stop

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Speaker 3: sleeping and do all the same things and don't enjoy

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Speaker 3: the things they normally would. Something that looks a bit

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Speaker 3: like depression is detectable in dogs and cats and elephants

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Speaker 3: and zoo animals, and even in things like zebrafish, which

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Speaker 3: are tiny little vertebrates. So evolution seems to have put

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Speaker 3: a depression like mode there, you know, a very long

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Speaker 3: time ago, and it's one of the oldest circuits in

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Speaker 3: the brain. When we look at the circuitry that drives depression.

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Speaker 3: What we find is it falls into a bigger category

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Speaker 3: of circuits that help the brain to defend against threats.

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Speaker 3: And in a nutshell, for every living thing, whether you're

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Speaker 3: a fish or a raccoon or a human, there are

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Speaker 3: sort of four main categories of things you can do

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Speaker 3: if a threat comes along. So let's say you're a

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Speaker 3: fish swimming along and a shark shows up. The first

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Speaker 3: thing you can do is you can freeze and hope

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Speaker 3: the shark doesn't see you, So that's freeze mode. If

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Speaker 3: the shark sees you and start chasing you, then you

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Speaker 3: have to go beyond freeze. You have to go into

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Speaker 3: this sort of the flight mode should be the escape mode,

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Speaker 3: and if the shark corners you, we've all seen that.

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Speaker 3: There are animals, you know, if you happen to get

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Speaker 3: a possum or a raccoon in your garage, there usually

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Speaker 3: will run away, But of course if they get cornered

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Speaker 3: and they feel like there's no way out, they will

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Speaker 3: fight very fiercely, and lots of animals do that. So

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Speaker 3: there is this third mode called fight. But the brain

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Speaker 3: needs a fourth mode to deal with situations that are unwinnable.

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Speaker 3: Sometimes You've tried freezing, you've tried fleeing, you've tried fighting.

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Speaker 3: But if at some point the brain decides you're not

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Speaker 3: going to win this fight and there's no running away,

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Speaker 3: there's no escaping, and you can't just ignore the problem,

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Speaker 3: the brain taps into a fourth mode that I'll call fold,

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Speaker 3: and there's a passive threat defense mode where the instincts

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Speaker 3: are all about losing your confidence, running home and hiding

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Speaker 3: in your burrow and keeping your head down and hoping

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Speaker 3: that something changes. This is the mode that is turned

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Speaker 3: on when people are fighting off in illness or a

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Speaker 3: major injury. So if they have surgery or if they're

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Speaker 3: fighting off in illness. Some people will actually have a

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Speaker 3: drop in their mood when they have an immunization, as

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Speaker 3: their immune system fires up to sort to deal with

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Speaker 3: the infection. But in any situation where the brain decides

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Speaker 3: that it needs to be hiding doubt in recovery and

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Speaker 3: recovering and keeping its head down, it will go into

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Speaker 3: this fold mode. Now that may be necessary to keep

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Speaker 3: you out of danger until the threat goes away, or

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Speaker 3: at least hopefully until the threat goes away. But the

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Speaker 3: problem that comes up in depression is when this becomes

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Speaker 3: a self perpetuating process and the circuits that drive fold mode,

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Speaker 3: which is a normal and useful defense mechanism for the

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Speaker 3: threats we can't win against. If those circuits get stuck

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Speaker 3: in an infinite feedback loop and just keep going and going,

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Speaker 3: then the person may still be stuck in depression weeks later,

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Speaker 3: months later, maybe even years later.

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Speaker 1: You once give me an example of falling off a

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Speaker 1: ship in the middle of the night to illustrate this

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Speaker 1: fold mode.

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Speaker 3: Yeah, so that's actually a great point. So there are

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Speaker 3: situations where we're we're going into this mode is really useful,

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Speaker 3: and every once in a while we're reading the news

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Speaker 3: about somebody who falls off the back of a ship

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Speaker 3: in the middle of the night and then miraculously gets

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Speaker 3: rescued in the morning. Now, if you or I fell

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Speaker 3: off the back of a ship in the middle of

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Speaker 3: the night, like a cruise ship or something, we'd probably

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Speaker 3: swim after the ship for a while and scream for

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Speaker 3: help and try and attract his attention. But if it

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Speaker 3: was really clear that the ship was sailing away and

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Speaker 3: no one could hear us, and we're stuck in the

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Speaker 3: middle of the sea, I mean, we're in a really

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Speaker 3: bad situation. It's really risky, and this is probably not

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Speaker 3: going to work out well. But our best chance of

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Speaker 3: survival is actually to fold, to curl up into a

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Speaker 3: ball and just wait and save your energy and hope

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Speaker 3: that something about the situation changes, hope you get rescued.

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Speaker 3: That mode is the same mode that we talk about

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Speaker 3: when we talk about depression, and in fact, when pharmaceutical

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Speaker 3: companies are developing new medications for depression, one of the

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Speaker 3: ways that they'll do animal testing to see if the

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Speaker 3: molecule helps depression is whether a thing called the forced

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Speaker 3: swim test, and the forced swim test, the animal, like

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Speaker 3: the mouse or whatever, is placed inside an air a

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Speaker 3: little beaker where they have to swim around and there's

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Speaker 3: nothing to stand on. Now, mice are quite good swimmers,

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Speaker 3: and they're also quite good floaters, so they'll swim and

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Speaker 3: swim around, and eventually, at some point they'll realize that

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Speaker 3: they're not going to get out of this situation, and

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Speaker 3: so they stop swimming around and they just give up

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Speaker 3: and float. And at that point the experimenter will stop

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Speaker 3: the stop watch and see how many minutes that took.

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Speaker 3: What's interesting is that there are breeds of mice who

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Speaker 3: are prone to depression and prone too are giving up quickly,

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Speaker 3: and most antidepressants, when the mice are on the antidepressant

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Speaker 3: still actually swim for a lot longer before giving up.

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Speaker 3: And so this forced swim test, which is really just

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Speaker 3: a way of tapping into how long before the animal

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Speaker 3: switches into this mode of folding and giving up and

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Speaker 3: waiting for something to change. That approach is a long

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Speaker 3: standing and standard way that people have searched for new

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Speaker 3: antidepressant medications over the last several decades.

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Speaker 2: Okay, terrific.

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Speaker 1: And so when we look at depression in this country

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Speaker 1: or around the world, what are the rates of depression?

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Speaker 2: Like, are things going up or down?

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Speaker 3: Yeah, so it's unfortunate that, I mean, the encouraging thing

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Speaker 3: over the last few decades is that compared to say,

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Speaker 3: the nineteen eighties, in the nineteen nineties when I started

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Speaker 3: doing brain imaging research, there's a lot less stigma around

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Speaker 3: mental health than there was, and that that's certainly very encouraging.

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Speaker 3: There are a lot more people seeking treatment than before,

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Speaker 3: and people are seeking treatments with medications and with psychotherapy

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Speaker 3: more more than ever. The problem is that this hasn't

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Speaker 3: changed the numbers at all. So despite the fact that

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Speaker 3: there's less stigma, despite the fact that people are coming

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Speaker 3: forward and taking antidepressants, and that in fact, antidepressants are

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Speaker 3: being used in sex quantities that they can be detected

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Speaker 3: with spectroscopes in the water supplies of cities and so on,

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Speaker 3: so they'll actually be able to go and they can

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Speaker 3: detect trace amounts of all these medications in city water supplies.

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Speaker 3: Despite all of this, the prevalence of depression and of

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Speaker 3: suicidal acts and suicidality has not gone down at all,

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Speaker 3: And in certain populations like younger folks under age twenty

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Speaker 3: and in the early twenties, the numbers for depression, anxiety,

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Speaker 3: and suicidality are going up rather than down. So we

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Speaker 3: definitely need to put the search on to understand how

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Speaker 3: depression works in the brain and really develop a new

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Speaker 3: generation of treatments because what we're having right now is

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Speaker 3: not moving the needle.

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Speaker 2: Why do you suppose the numbers are going up?

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Speaker 3: There are a lot of different possibilities for why that is.

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Speaker 3: I think we could probably have a whole other podcast

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Speaker 3: on what that is. In a nutshell, there are more

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Speaker 3: There seem to be more situations where people feel like

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Speaker 3: the fight is unwinnable. When I see that it numbers

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Speaker 3: for depression and suicidality going up, it's sort of an

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Speaker 3: index of a number of people who feel like they

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Speaker 3: are losing it life and that there's no way out

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Speaker 3: for them. So it is a bit of a barometer

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Speaker 3: of social health in that way. Some people have also

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Speaker 3: attributed to increased stressors around social media use and so on,

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Speaker 3: and some people have even attributed to things like changes

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Speaker 3: in the composition of the bacteria that live within our guts,

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Speaker 3: some of which appear to have a protective effect against depressions.

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Speaker 3: So there are a lot of theories out there, but

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Speaker 3: I wouldn't say anyone has solved the mysteries of what

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Speaker 3: it is. There are lots of people posing everything from

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Speaker 3: social factors to psychological factors to biological factors like literally

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Speaker 3: write down to the bacteria in a person's gut.

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Speaker 1: So what do you think about the pharmaceutical treatments for depression?

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Speaker 1: Are they are they useful? Are they neutral?

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Speaker 3: Well, I would say that I can give you what

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Speaker 3: the numbers say. So if a person comes into their

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Speaker 3: family doctor with an episode of depression and they try

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Speaker 3: an antidepressant. There was a famous study about fifteen years

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Speaker 3: ago called star d Let out of the University of

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Speaker 3: Texas Southwestern and they found that about two thirds of

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Speaker 3: people could get to remission from depression after trying one

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Speaker 3: medication or two medications, or three medications or four medications

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Speaker 3: one after the other. But the numbers really drop precipit

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Speaker 3: so about one third of people would get better trying

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Speaker 3: the first medication they ever tried, only about one third

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Speaker 3: about a quarter of people would get better on the

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Speaker 3: second medication they tried. But by the time you've tried

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Speaker 3: two medications without success, the third and the fourth one

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Speaker 3: are down to, you know, around eight to twelve percent

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Speaker 3: success rates, not particularly high at all. So we're unfortunately

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Speaker 3: the situation where the medications tend to work by fairly

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Speaker 3: similar mechanisms in terms of boosting serotonin levels or boosting

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Speaker 3: nor at be inefferent levels or dobamine levels and so

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Speaker 3: on and so. Yes, you try to influence the person's

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Speaker 3: oppression by influencing these neurotransmitters in the brain, but at

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Speaker 3: least one third of people don't get any benefit from them,

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Speaker 3: and unfortunately a lot of people relapse and a very

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Speaker 3: large percentage of people, About twenty five percent of people

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Speaker 3: stop taking medications early because of side effects. So I

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Speaker 3: don't want to run down medications because the upside is that,

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Speaker 3: you know, it's in some ways, it's quite remarkable that

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Speaker 3: you can take somebody who's despairing about where their life

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Speaker 3: is going, and all you ask them to do is

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Speaker 3: take ten seconds out of their day to take a

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Speaker 3: serotonin boosting medication or a or an effort in boosing

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Speaker 3: medication just at bedtime with their toothbrush, and it is

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Speaker 3: quite remarkable that just by doing that one little thing,

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Speaker 3: a certain percentity of people will emerge from depressed, dispar

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Speaker 3: and suicidality and be able to face the world again.

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Speaker 3: So that's the upside of it. The downside is that

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Speaker 3: there's also a very large number of people who don't

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Speaker 3: get better on the medications, and a very large number

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Speaker 3: of people who can't tolerate the medications.

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Speaker 1: So tell me about recent breakthroughs that are understanding.

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Speaker 3: So we're in what I would argue is actually one

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Speaker 3: of the most exciting periods of discovery within all of

440
00:23:33,960 --> 00:23:36,920
Speaker 3: within all of medicine. So it's psychiatry, and in particular

441
00:23:36,920 --> 00:23:41,120
Speaker 3: a field called interventional psychiatry is now looking at all

442
00:23:41,160 --> 00:23:44,760
Speaker 3: the traditional disorders like depression, anxiety, and so on in

443
00:23:44,880 --> 00:23:47,280
Speaker 3: terms of brain circuitry and in terms of brain function,

444
00:23:48,400 --> 00:23:51,240
Speaker 3: and thanks to twenty five years of brain imaging research,

445
00:23:51,240 --> 00:23:54,200
Speaker 3: we're actually starting to get really lovely maps of where

446
00:23:54,359 --> 00:23:57,040
Speaker 3: stuff happens in the brain and what brain circuits are

447
00:23:57,040 --> 00:24:02,080
Speaker 3: involved in depression, anxiety, OCD, post traumatic stress disorder, or

448
00:24:02,119 --> 00:24:06,960
Speaker 3: eating disorders, pretty much most of the major categories of

449
00:24:07,119 --> 00:24:10,240
Speaker 3: mental health disorders. We are starting to get really great

450
00:24:10,280 --> 00:24:12,719
Speaker 3: maps of what areas of the brain are affected in them.

451
00:24:13,160 --> 00:24:15,399
Speaker 3: The thing that's making that knowledge useful is that we're

452
00:24:15,440 --> 00:24:18,640
Speaker 3: also starting to really take advantage now of a new

453
00:24:18,720 --> 00:24:24,119
Speaker 3: generation of brain stimulation treatments inspired by the kinds of

454
00:24:24,160 --> 00:24:26,320
Speaker 3: cases that I told you about at the beginning of

455
00:24:26,359 --> 00:24:30,280
Speaker 3: our conversation, which can go into those circuits which may

456
00:24:30,280 --> 00:24:34,520
Speaker 3: be overactive or underactive, and can actually stimulate them and

457
00:24:34,720 --> 00:24:38,959
Speaker 3: reset them back to their normal pattern of activity. So

458
00:24:39,119 --> 00:24:42,520
Speaker 3: these new generation of treatments are brain stimulation treatments, and

459
00:24:42,560 --> 00:24:46,280
Speaker 3: what's important about them is they're anatomically precise. Some of them,

460
00:24:46,400 --> 00:24:51,720
Speaker 3: as I mentioned before, involve implantable devices like deep brain stimulators,

461
00:24:51,960 --> 00:24:54,360
Speaker 3: and for the last twenty years, people have been pioneering

462
00:24:54,440 --> 00:24:56,239
Speaker 3: and starting to come up with ways that they can

463
00:24:56,240 --> 00:24:59,320
Speaker 3: actually implant little pacemakers in the brains of people who

464
00:24:59,320 --> 00:25:02,560
Speaker 3: have very serious forms of depression where nothing has worked,

465
00:25:03,080 --> 00:25:06,480
Speaker 3: and these deep brain stimulators have caused quite remarkable ability

466
00:25:06,520 --> 00:25:08,600
Speaker 3: of people to turn around and immerge from their depression.

467
00:25:09,240 --> 00:25:10,800
Speaker 3: But of course we also have the issue that not

468
00:25:10,880 --> 00:25:13,160
Speaker 3: everybody wants to have a pacemaker and plant in their brain,

469
00:25:13,240 --> 00:25:16,199
Speaker 3: and so it would be really really useful if they

470
00:25:16,200 --> 00:25:19,919
Speaker 3: could undergo a different form of treatment that was non invasive.

471
00:25:20,359 --> 00:25:22,399
Speaker 3: And so the other kind of treatment that's really taking

472
00:25:22,400 --> 00:25:25,679
Speaker 3: off right now involves a treatment approved by the FDA

473
00:25:25,920 --> 00:25:30,600
Speaker 3: in two thousand and eight called transcranial magnetic stimulation. Transcranial

474
00:25:30,640 --> 00:25:36,359
Speaker 3: magnetic stimulation involves using a powerful focus magnetic pulse generator

475
00:25:37,119 --> 00:25:39,000
Speaker 3: place it looks like a little ping pong paddle. It's

476
00:25:39,040 --> 00:25:41,680
Speaker 3: sort of placed against the scalp. You place it over

477
00:25:41,760 --> 00:25:44,520
Speaker 3: the target circuit that you want to stimulate, and with

478
00:25:44,600 --> 00:25:48,080
Speaker 3: the magnetic pulses you're able to actually stimulate and activate

479
00:25:48,119 --> 00:25:51,280
Speaker 3: target circuits in the brain without needing any surgery. They're

480
00:25:51,359 --> 00:25:53,680
Speaker 3: quite powerful, so even though they're magnetic pulses. These are

481
00:25:53,680 --> 00:25:56,760
Speaker 3: not fridge magnets. Like if you were to place this

482
00:25:57,000 --> 00:26:00,600
Speaker 3: paddle over the precise spot on your brain that moves

483
00:26:00,600 --> 00:26:03,800
Speaker 3: your thumb, and I were to press the button and

484
00:26:03,880 --> 00:26:06,160
Speaker 3: cause a couple of little pulses, you would actually see

485
00:26:06,560 --> 00:26:09,280
Speaker 3: your thumb or your hand move with every single pulse.

486
00:26:10,080 --> 00:26:12,320
Speaker 3: So these are ways of actually stimulating target reasons in

487
00:26:12,359 --> 00:26:15,320
Speaker 3: the brain. And by stimulating them over and over again

488
00:26:15,400 --> 00:26:18,280
Speaker 3: hundreds of times a day, you can gradually strengthen the

489
00:26:18,320 --> 00:26:22,240
Speaker 3: connections in areas of the brain that require strengthening, or

490
00:26:22,359 --> 00:26:24,879
Speaker 3: you can reduce the strength of the connections and areas

491
00:26:24,880 --> 00:26:28,400
Speaker 3: that I guess are overconnected. And with these two approaches,

492
00:26:28,480 --> 00:26:30,679
Speaker 3: you can try to return the brain or reset the

493
00:26:30,720 --> 00:26:34,600
Speaker 3: brain back to its normal pattern of activity that occurs

494
00:26:34,640 --> 00:26:38,440
Speaker 3: when they are not in this mode of despair and folding.

495
00:26:39,160 --> 00:26:42,960
Speaker 1: And how is this figured out? About which brain areas

496
00:26:43,080 --> 00:26:43,760
Speaker 1: to zap.

497
00:26:44,880 --> 00:26:48,040
Speaker 3: So the work on this began all the way back

498
00:26:48,040 --> 00:26:50,600
Speaker 3: in the nineteen eighties when they started using pet scanners,

499
00:26:51,040 --> 00:26:54,320
Speaker 3: which injects a radioactive dye to look at the metabolism

500
00:26:54,359 --> 00:26:56,879
Speaker 3: of the brain, and they were able to compare the

501
00:26:56,920 --> 00:27:00,760
Speaker 3: brain activity of people with depression people who are not

502
00:27:00,840 --> 00:27:03,680
Speaker 3: in depression, and so the first maps of these came

503
00:27:03,720 --> 00:27:06,280
Speaker 3: out in the late nineteen eighties and early nineteen nineties,

504
00:27:06,359 --> 00:27:09,280
Speaker 3: and they pinpointed a set of areas in the frontal

505
00:27:09,280 --> 00:27:11,840
Speaker 3: lobes and also elsewhere in the brain that seemed to

506
00:27:11,840 --> 00:27:16,320
Speaker 3: be consistently underactive in people with depression. They also pinpointed

507
00:27:16,720 --> 00:27:20,040
Speaker 3: areas of the brain that were consistently overactive in people

508
00:27:20,040 --> 00:27:23,040
Speaker 3: with depression. Those ones appear to be deeper in and

509
00:27:23,080 --> 00:27:25,520
Speaker 3: this led to a new generation of treatments where people

510
00:27:25,640 --> 00:27:29,960
Speaker 3: use the transcranial magnetic stimulation devices to target the frontal

511
00:27:29,960 --> 00:27:32,760
Speaker 3: lobe areas near the surface because the magnetic pulses could

512
00:27:32,800 --> 00:27:35,600
Speaker 3: read them. They also went to the surgeons and began

513
00:27:35,760 --> 00:27:39,240
Speaker 3: using the deep brain simulator electrodes, which despite their name

514
00:27:39,400 --> 00:27:42,600
Speaker 3: as stimulators, can actually be used to inhibit and disrupt

515
00:27:43,000 --> 00:27:45,760
Speaker 3: areas of the brain that are overactive, and so they

516
00:27:45,760 --> 00:27:47,680
Speaker 3: were able to implant these in the areas of the

517
00:27:47,680 --> 00:27:51,000
Speaker 3: brain that were deeper and overactive in depression and use

518
00:27:51,080 --> 00:27:54,840
Speaker 3: them to reset their activity. So I recently did an

519
00:27:54,840 --> 00:27:58,959
Speaker 3: episode on how brains simulate the future. This is one

520
00:27:58,960 --> 00:28:02,000
Speaker 3: of the main jobs of brains is to simulate and

521
00:28:02,000 --> 00:28:06,160
Speaker 3: evaluate possible futures. What's your interpretation of what happens when

522
00:28:06,200 --> 00:28:09,720
Speaker 3: somebody is depressed in terms of the futures that they

523
00:28:09,760 --> 00:28:15,120
Speaker 3: are simulating. So that's a fascinating question, and I think

524
00:28:15,320 --> 00:28:17,679
Speaker 3: there actually are some really lovely brain imaging studies that

525
00:28:17,720 --> 00:28:21,280
Speaker 3: we're done on this about ten years ago, led by

526
00:28:21,320 --> 00:28:24,720
Speaker 3: Adam Gazzale and some other folks over at UCSF. What

527
00:28:24,840 --> 00:28:27,920
Speaker 3: they noticed was that perhaps in your discussion you talked

528
00:28:27,920 --> 00:28:30,439
Speaker 3: about a network of areas in the brain called the

529
00:28:30,600 --> 00:28:34,760
Speaker 3: default mode network. The default mode network is named that

530
00:28:34,800 --> 00:28:36,800
Speaker 3: because it seems to be one of the most you know,

531
00:28:36,920 --> 00:28:38,320
Speaker 3: it's the area of the brain that is on by

532
00:28:38,360 --> 00:28:40,520
Speaker 3: default when we're not doing anything else. So if you

533
00:28:40,640 --> 00:28:42,440
Speaker 3: or I are sitting in a room quietly and there's

534
00:28:42,480 --> 00:28:45,320
Speaker 3: nothing going on, our default mode network turns on. And

535
00:28:45,360 --> 00:28:48,120
Speaker 3: as we've all experienced that involved what happens in our

536
00:28:48,160 --> 00:28:50,160
Speaker 3: minds is our brains start thinking about the past and

537
00:28:50,160 --> 00:28:52,720
Speaker 3: thinking about the future and making plans and thinking about

538
00:28:52,720 --> 00:28:53,560
Speaker 3: what may take place.

539
00:28:53,920 --> 00:28:55,800
Speaker 2: There are two pathways by which we do that.

540
00:28:55,840 --> 00:28:58,760
Speaker 3: There's a so called reward pathway where our brain thinks

541
00:28:58,760 --> 00:29:01,480
Speaker 3: about opportunities and things we might start to want or

542
00:29:01,520 --> 00:29:03,320
Speaker 3: desire to get us up out of our seats and

543
00:29:03,320 --> 00:29:07,000
Speaker 3: get going. But there's also a second pathway called the

544
00:29:07,080 --> 00:29:10,240
Speaker 3: non reward pathway, whose job it is entirely to think

545
00:29:10,280 --> 00:29:13,480
Speaker 3: about non rewarding outcomes. Things could go wrong, fires I

546
00:29:13,520 --> 00:29:15,360
Speaker 3: have to put out problems in my life, things that

547
00:29:15,400 --> 00:29:18,040
Speaker 3: I should be motivated to go and sort out. And

548
00:29:18,080 --> 00:29:20,160
Speaker 3: we need both of those to work in balance. So

549
00:29:20,200 --> 00:29:23,080
Speaker 3: we both need the ability to come up with ideas

550
00:29:23,080 --> 00:29:25,760
Speaker 3: for opportunities and things that we desire to do, but

551
00:29:25,800 --> 00:29:29,240
Speaker 3: we also need to be guided by all the problems

552
00:29:29,240 --> 00:29:31,280
Speaker 3: in life, all the things that we really need to

553
00:29:31,280 --> 00:29:34,360
Speaker 3: be motivated to take care of. And with a balance

554
00:29:34,360 --> 00:29:36,920
Speaker 3: between those two, we can both pursue opportunities in the future,

555
00:29:36,960 --> 00:29:40,680
Speaker 3: and we can also avoid threats and problems and resolve them.

556
00:29:41,240 --> 00:29:44,240
Speaker 3: The problem and depression occurs when this so called non

557
00:29:44,280 --> 00:29:46,760
Speaker 3: reward pathway, whose whole job is to think about all

558
00:29:46,840 --> 00:29:50,000
Speaker 3: negative consequences, things that are going wrong, things that could

559
00:29:50,000 --> 00:29:53,120
Speaker 3: screw up, It can get trapped into sort of self

560
00:29:53,160 --> 00:29:56,440
Speaker 3: perpetuating feedback loop. So the circuit in the brain is

561
00:29:56,520 --> 00:29:59,000
Speaker 3: arranged as a bit of a loop from the frontal

562
00:29:59,040 --> 00:30:02,240
Speaker 3: lobes going down into the reward and motivational structures of

563
00:30:02,240 --> 00:30:06,600
Speaker 3: the brain and as if it gets stuck in a loop.

564
00:30:06,640 --> 00:30:09,520
Speaker 3: What happens is the person experience is just finding that

565
00:30:09,720 --> 00:30:11,560
Speaker 3: even though there may be ninety nine things that are

566
00:30:11,560 --> 00:30:14,440
Speaker 3: going well in the person's life, their brain will find

567
00:30:14,480 --> 00:30:16,719
Speaker 3: the one thing that's going wrong and it will get

568
00:30:16,800 --> 00:30:18,440
Speaker 3: stuck on it, and it will just loop on it

569
00:30:18,480 --> 00:30:20,800
Speaker 3: over and over and over again. I think most of

570
00:30:20,880 --> 00:30:24,000
Speaker 3: us know somebody as family, friends, colleagues, maybe even ourselves

571
00:30:24,000 --> 00:30:25,800
Speaker 3: who tend to do that, who are always really good

572
00:30:25,840 --> 00:30:27,719
Speaker 3: at spotting the one problem and getting stuck on it.

573
00:30:28,320 --> 00:30:31,080
Speaker 3: But in depression it becomes true to a pathological extent

574
00:30:31,120 --> 00:30:33,240
Speaker 3: where they get so stuck on it that even with effort,

575
00:30:33,280 --> 00:30:38,280
Speaker 3: they cannot pull themselves out of the negative circle of thoughts,

576
00:30:38,280 --> 00:30:42,520
Speaker 3: which we call by the technical term ruminations. So in depression,

577
00:30:43,480 --> 00:30:45,920
Speaker 3: this non reward pathway has gotten stuck in a loop,

578
00:30:45,920 --> 00:30:48,800
Speaker 3: and what the person experiences is an endless circle of

579
00:30:48,880 --> 00:30:52,920
Speaker 3: ruminations and self criticism and thoughts about all the possible

580
00:30:53,000 --> 00:30:55,240
Speaker 3: futures that will go wrong and all the past things

581
00:30:55,240 --> 00:30:57,840
Speaker 3: that have gone wrong. And it just becomes very difficult

582
00:30:57,840 --> 00:30:59,880
Speaker 3: to pull yourself out of this even when you need to.

583
00:31:00,240 --> 00:31:04,560
Speaker 1: And so what is the transcranial magnetic stimulation doing when

584
00:31:04,600 --> 00:31:08,320
Speaker 1: you are hitting a particular area, is it giving a

585
00:31:08,440 --> 00:31:11,960
Speaker 1: second bite at the apple for that area to rewire?

586
00:31:12,520 --> 00:31:15,160
Speaker 1: Is it simply making the area more plastic so that

587
00:31:15,200 --> 00:31:18,640
Speaker 1: it has an opportunity to wire up in a more

588
00:31:18,680 --> 00:31:20,160
Speaker 1: beneficial way the next time around.

589
00:31:20,960 --> 00:31:23,600
Speaker 3: So I'll give you our best guess as to what's

590
00:31:23,600 --> 00:31:26,360
Speaker 3: happening right now. As with many things in psychiatry, we

591
00:31:26,440 --> 00:31:29,240
Speaker 3: discovered that these things worked long before we actually figured

592
00:31:29,280 --> 00:31:33,480
Speaker 3: out why they worked. But the original areas of the

593
00:31:33,520 --> 00:31:36,720
Speaker 3: brain that we stimulated were targeted because they just seem

594
00:31:36,760 --> 00:31:38,960
Speaker 3: to be underactive in depression. So the theory was, look,

595
00:31:38,960 --> 00:31:41,760
Speaker 3: they're underactive, let's use this brain stimulator. Let's stimulate them,

596
00:31:41,840 --> 00:31:43,800
Speaker 3: let's turn them back on, and then all will be well.

597
00:31:44,520 --> 00:31:46,800
Speaker 3: Later on, we discovered that what these areas really seem

598
00:31:46,840 --> 00:31:50,680
Speaker 3: to be associated with is courage and resilience. In other words,

599
00:31:50,760 --> 00:31:54,440
Speaker 3: people who happened just by chance to have more gray

600
00:31:54,480 --> 00:31:57,280
Speaker 3: matter or more gray matter in these areas, they're more

601
00:31:57,320 --> 00:32:00,760
Speaker 3: resilient distress. They have better ability to cope. These brain

602
00:32:00,840 --> 00:32:04,040
Speaker 3: areas in the frontal lobes are engaged every time we

603
00:32:04,080 --> 00:32:06,520
Speaker 3: do a thing called cognitive control, which is our ability

604
00:32:06,560 --> 00:32:09,200
Speaker 3: to self regulate our thoughts and our behaviors and emotions.

605
00:32:09,640 --> 00:32:12,280
Speaker 3: In fact, for those of you who've tried MINDFULSS meditation,

606
00:32:12,320 --> 00:32:14,280
Speaker 3: if you've ever sat in a chair and tried to

607
00:32:14,320 --> 00:32:17,400
Speaker 3: not ruminate and tried to focus on your breathing. Every

608
00:32:17,400 --> 00:32:20,320
Speaker 3: time you notice that your mind is wandering, and you

609
00:32:20,400 --> 00:32:23,240
Speaker 3: shut down the ruminations and come back to your breathing again,

610
00:32:23,560 --> 00:32:26,120
Speaker 3: you turn on this network of areas. It looks like

611
00:32:26,160 --> 00:32:28,360
Speaker 3: what we're doing with TMS is actually not so much

612
00:32:28,440 --> 00:32:31,680
Speaker 3: pushing happiness into the brain or pulling anxiety out, but

613
00:32:31,720 --> 00:32:35,920
Speaker 3: more generally strengthening the very same network that is activated

614
00:32:36,000 --> 00:32:39,200
Speaker 3: when you do MINDFULSS meditation. And so when I talk

615
00:32:39,320 --> 00:32:41,960
Speaker 3: to patients about what it's like for them after the

616
00:32:42,080 --> 00:32:44,680
Speaker 3: TMS has worked, they talk a lot about how something

617
00:32:44,720 --> 00:32:47,000
Speaker 3: stressful happen this week, and normally it would have ruined

618
00:32:47,040 --> 00:32:49,080
Speaker 3: my whole week, but I noticed that I just got

619
00:32:49,080 --> 00:32:50,959
Speaker 3: over it. I kind of thought about it and realized

620
00:32:51,000 --> 00:32:52,800
Speaker 3: it wasn't as bad as and I was able to

621
00:32:52,840 --> 00:32:55,640
Speaker 3: kind of cope with it. They describe it as having

622
00:32:55,680 --> 00:32:58,400
Speaker 3: more coping capacity, And so it looks like the effects

623
00:32:58,440 --> 00:33:01,040
Speaker 3: of TMS on depression, at least with the standard areas

624
00:33:01,120 --> 00:33:03,840
Speaker 3: might be somewhat indirect. You're not so much pushing happiness

625
00:33:03,840 --> 00:33:07,120
Speaker 3: in or taking anxiety out, but you are strengthening a

626
00:33:07,160 --> 00:33:10,320
Speaker 3: sort of mental muscle for cognitive control. And as a result,

627
00:33:10,360 --> 00:33:13,800
Speaker 3: people just generally get better at self regulating their thoughts

628
00:33:13,840 --> 00:33:16,360
Speaker 3: and behaviors and emotions, and they can cope with more stress.

629
00:33:16,760 --> 00:33:19,000
Speaker 3: So things don't feel quite as defeating, things don't look

630
00:33:19,040 --> 00:33:19,560
Speaker 3: quite as bad.

631
00:33:20,760 --> 00:33:24,120
Speaker 1: I've been sort of playing with a different interpretation slightly

632
00:33:24,160 --> 00:33:28,600
Speaker 1: about it, which is that you are, to phrase it colloquially,

633
00:33:28,640 --> 00:33:32,200
Speaker 1: you're sort of loosening up a network that has found

634
00:33:32,200 --> 00:33:37,920
Speaker 1: itself getting into a particular way, a particular structure, and

635
00:33:37,960 --> 00:33:41,560
Speaker 1: what you're doing is reintroducing plasticity to that area so

636
00:33:41,720 --> 00:33:45,560
Speaker 1: that you have a chance of things running correctly through there.

637
00:33:46,000 --> 00:33:50,240
Speaker 1: And with TMS, as we know, sometimes the first treatment

638
00:33:50,400 --> 00:33:53,880
Speaker 1: doesn't work, but the second treatment does. My view on

639
00:33:53,920 --> 00:33:57,120
Speaker 1: that is that it's possible that after the first time,

640
00:33:57,520 --> 00:34:04,240
Speaker 1: the system reconverges in to some pathological wiring, and then

641
00:34:04,320 --> 00:34:06,280
Speaker 1: you know, if you do it again, you're getting another

642
00:34:06,440 --> 00:34:09,960
Speaker 1: chance to have it find better wiring.

643
00:34:11,000 --> 00:34:13,160
Speaker 3: Yeah. I'm really glad you brought that up, because I

644
00:34:13,239 --> 00:34:15,759
Speaker 3: think that actually lines up really well with a very

645
00:34:15,760 --> 00:34:21,120
Speaker 3: recent discovery that's still quite new about what is happening

646
00:34:21,400 --> 00:34:25,120
Speaker 3: for people who are trying a second form of OURTMS

647
00:34:25,120 --> 00:34:27,359
Speaker 3: that kicks in when the first one doesn't work. So

648
00:34:27,640 --> 00:34:32,600
Speaker 3: when I start rTMS repetitive transcranial magnetic stimulation, it's effectively

649
00:34:32,640 --> 00:34:35,680
Speaker 3: TMS treatment but using these repetitive pulses. So some people

650
00:34:35,719 --> 00:34:38,040
Speaker 3: will call it rTMS, and some people will simply just

651
00:34:38,480 --> 00:34:41,080
Speaker 3: abbreviate it to TMS. But we're talking about using this

652
00:34:41,160 --> 00:34:43,960
Speaker 3: non invasive stimulation. So when a person goes through and

653
00:34:43,960 --> 00:34:46,920
Speaker 3: does the treatment using the standard parameters that I talked about,

654
00:34:47,200 --> 00:34:49,080
Speaker 3: sometimes it works, and yet there is a percentage of

655
00:34:49,120 --> 00:34:51,879
Speaker 3: people where it doesn't work. What we've noticed that those

656
00:34:51,880 --> 00:34:55,480
Speaker 3: people tend to have higher scales on rumination negative ruminations

657
00:34:55,480 --> 00:34:58,440
Speaker 3: ABAD life, and a lovely study came out by a

658
00:34:58,480 --> 00:35:00,840
Speaker 3: group led by Andy Lukter at You where he was

659
00:35:00,880 --> 00:35:04,720
Speaker 3: able to identify that these people have higher rumination scores.

660
00:35:06,239 --> 00:35:08,640
Speaker 3: They then move the coil to a different area, so

661
00:35:08,680 --> 00:35:10,920
Speaker 3: instead of stimulating the first area they talk about, they

662
00:35:10,960 --> 00:35:14,160
Speaker 3: go to a different brain area which actually sits within

663
00:35:14,239 --> 00:35:17,040
Speaker 3: this non reward circuit that we were talking about before,

664
00:35:17,520 --> 00:35:20,439
Speaker 3: and instead of trying to stimulate and strengthen it. Sure enough.

665
00:35:20,440 --> 00:35:22,880
Speaker 3: What they do is they try and inhibit and disrupt

666
00:35:22,920 --> 00:35:25,279
Speaker 3: the activity of this area. So they are trying to

667
00:35:25,400 --> 00:35:28,719
Speaker 3: disrupt and break up the feedback loop that they call

668
00:35:28,800 --> 00:35:32,560
Speaker 3: the non reward attractor state. It's in fact a professor

669
00:35:32,640 --> 00:35:35,320
Speaker 3: named Edmund Rolls out of Cambridge by the way just described,

670
00:35:35,440 --> 00:35:37,319
Speaker 3: he came up with a theory of depression which is

671
00:35:37,400 --> 00:35:39,200
Speaker 3: very similar to what you describe. He called it the

672
00:35:39,640 --> 00:35:43,560
Speaker 3: non reward attractor theory of depression. That non reward circuit.

673
00:35:43,880 --> 00:35:46,280
Speaker 3: The more it runs and the more it dwells on things,

674
00:35:46,280 --> 00:35:48,640
Speaker 3: the more it strengthens the connections in and of itself,

675
00:35:48,719 --> 00:35:51,920
Speaker 3: so it becomes self strengthening, self perpetuating, and you're just

676
00:35:51,960 --> 00:35:54,359
Speaker 3: going to get stuck in this so called attractor state

677
00:35:54,520 --> 00:35:56,360
Speaker 3: and not be able to get out of it. The

678
00:35:56,400 --> 00:35:59,240
Speaker 3: solution with TMS would be to put the coil over

679
00:35:59,480 --> 00:36:02,279
Speaker 3: those areas is and apply some pulses of stimulation, not

680
00:36:02,320 --> 00:36:04,319
Speaker 3: to strengthen the pathway that's not what we want, but

681
00:36:04,400 --> 00:36:08,839
Speaker 3: to disrupt and weaken the connections through a neuroplasticity to

682
00:36:08,880 --> 00:36:11,120
Speaker 3: the point where the person can now pull themselves out again.

683
00:36:11,640 --> 00:36:15,840
Speaker 1: That's your interpretation of what transcrinal meganing stimulation does, right.

684
00:36:15,800 --> 00:36:17,840
Speaker 3: Yeah, so we're still figuring this out. But what we

685
00:36:17,880 --> 00:36:20,160
Speaker 3: think is that for some people, when you strengthen the

686
00:36:20,200 --> 00:36:24,480
Speaker 3: first circuit and they regain their cognitive control, that circuit

687
00:36:24,560 --> 00:36:26,920
Speaker 3: is connected to the non reward circuit, so they can

688
00:36:26,960 --> 00:36:29,600
Speaker 3: then use their cognitive control to do this work themselves

689
00:36:29,640 --> 00:36:32,640
Speaker 3: of popping themselves out at this tractor state. In other people,

690
00:36:32,719 --> 00:36:35,680
Speaker 3: for whatever reason, these two pathways aren't really very well connected,

691
00:36:35,719 --> 00:36:38,160
Speaker 3: so they kind of operate independently. So you strengthen the

692
00:36:38,160 --> 00:36:41,080
Speaker 3: first pathway, they get more coping capacity, but the problem

693
00:36:41,080 --> 00:36:43,960
Speaker 3: is they're still stuck in these negative terminations. Then you

694
00:36:44,000 --> 00:36:46,440
Speaker 3: bring them back again, you move the stimulator over to

695
00:36:46,480 --> 00:36:49,480
Speaker 3: this other pathway. I actually had a patient who described

696
00:36:49,520 --> 00:36:51,920
Speaker 3: as saying this for your first treatment didn't work, but

697
00:36:51,960 --> 00:36:54,800
Speaker 3: the second one you gave me over this non reward pathway.

698
00:36:55,480 --> 00:36:57,680
Speaker 3: He said, I'm definitely one of those people you talked

699
00:36:57,680 --> 00:37:00,399
Speaker 3: about who always finds the one negative thing the room,

700
00:37:00,440 --> 00:37:02,919
Speaker 3: and if I see it, it's like a negative he said,

701
00:37:02,960 --> 00:37:05,640
Speaker 3: it's like an escalator. I'm forcing it on the escalator

702
00:37:05,680 --> 00:37:08,000
Speaker 3: and ride it down, down, down, all the way to

703
00:37:08,040 --> 00:37:09,879
Speaker 3: the bottom, and then I'm just stuck there. I could

704
00:37:09,880 --> 00:37:12,520
Speaker 3: be stuck there for days or weeks. And after I

705
00:37:12,560 --> 00:37:15,520
Speaker 3: finished the course of treatment, something really horrible happened, and

706
00:37:15,560 --> 00:37:17,120
Speaker 3: I thought, oh boy, here we go. I'm going to

707
00:37:17,120 --> 00:37:19,600
Speaker 3: be dragged down the escalator. And it just didn't happen.

708
00:37:19,880 --> 00:37:21,919
Speaker 3: I noticed the way he said it. He says, it's

709
00:37:22,000 --> 00:37:23,920
Speaker 3: like I walked up to the top of this escalator,

710
00:37:23,960 --> 00:37:26,000
Speaker 3: I saw where it was going, and I realized I

711
00:37:26,040 --> 00:37:28,160
Speaker 3: didn't want to go down there, and so my brain

712
00:37:28,239 --> 00:37:31,520
Speaker 3: just kept going. And I think what's interesting on the

713
00:37:31,520 --> 00:37:33,719
Speaker 3: brain imaging studies, of course, is if you scan people

714
00:37:33,760 --> 00:37:36,160
Speaker 3: before and after, what you find is exactly what you described,

715
00:37:36,440 --> 00:37:40,200
Speaker 3: that the connections between within this circuit are actually getting

716
00:37:40,200 --> 00:37:43,360
Speaker 3: disrupted and weakened. So the circuit's still there and functioning,

717
00:37:43,360 --> 00:37:45,960
Speaker 3: but it's not getting stuck in this attractor state or

718
00:37:46,000 --> 00:37:48,359
Speaker 3: this loop. So I think it actually lines up really

719
00:37:48,400 --> 00:37:50,880
Speaker 3: well with the account you just described. In the one case,

720
00:37:51,000 --> 00:37:53,960
Speaker 3: plasticity being used to strengthen the person's ability to control

721
00:37:54,000 --> 00:37:56,799
Speaker 3: their thoughts. But if that doesn't work in the other case,

722
00:37:56,840 --> 00:37:59,319
Speaker 3: you can then go directly to the area that's stuck

723
00:37:59,320 --> 00:38:01,800
Speaker 3: in a loop in the first place and use another

724
00:38:01,840 --> 00:38:04,800
Speaker 3: form of plasticity to weaken those connections and loosen them

725
00:38:04,920 --> 00:38:06,480
Speaker 3: so the person can come out of it again.

726
00:38:24,440 --> 00:38:28,040
Speaker 1: This is very cool because originally with depression, I mean,

727
00:38:28,040 --> 00:38:30,280
Speaker 1: I think it's always been this way historically, that people,

728
00:38:30,480 --> 00:38:33,000
Speaker 1: let's say loved ones who are with somebody who's depressed,

729
00:38:33,360 --> 00:38:35,399
Speaker 1: feel like, hey, we should just be able to talk

730
00:38:35,440 --> 00:38:37,080
Speaker 1: to the person out of this, just say hey, look

731
00:38:37,120 --> 00:38:38,120
Speaker 1: at the bright side and so on.

732
00:38:38,520 --> 00:38:39,840
Speaker 2: That doesn't work.

733
00:38:40,520 --> 00:38:44,360
Speaker 1: And so this idea of being able to help somebody

734
00:38:45,520 --> 00:38:49,359
Speaker 1: buy let's say, loosening up circuits in the brain, doing

735
00:38:49,400 --> 00:38:51,480
Speaker 1: other things, you know, getting someone out of an attractor

736
00:38:51,560 --> 00:38:57,880
Speaker 1: state non invasively is so promising. What do you predict

737
00:38:58,000 --> 00:39:00,759
Speaker 1: is going to be the field in forty years from

738
00:39:00,840 --> 00:39:02,480
Speaker 1: now when you're elderly.

739
00:39:03,360 --> 00:39:06,719
Speaker 3: Oh wow, that's really interesting. I'll get to that in

740
00:39:06,760 --> 00:39:09,120
Speaker 3: a moment, but I want to just come back and

741
00:39:09,200 --> 00:39:11,040
Speaker 3: highlight that I think you've really hit the nail on

742
00:39:11,080 --> 00:39:13,759
Speaker 3: the head with this, that every one of us has

743
00:39:13,800 --> 00:39:16,560
Speaker 3: tried to talk someone who's despairing out of the respair.

744
00:39:16,600 --> 00:39:19,440
Speaker 3: We've all tried to do it, and we've all been

745
00:39:19,520 --> 00:39:22,000
Speaker 3: sort of signed and frustrated, going, why are you fighting

746
00:39:22,040 --> 00:39:24,040
Speaker 3: us on this? I keep trying to tell you all

747
00:39:24,080 --> 00:39:25,600
Speaker 3: the things that are good in life and reminds you

748
00:39:25,600 --> 00:39:27,319
Speaker 3: of them, and it's almost like you want your brain

749
00:39:27,400 --> 00:39:29,160
Speaker 3: wants to just go to the one negative thing and

750
00:39:29,239 --> 00:39:31,720
Speaker 3: stuck there. You've had that experience in talking to somebody.

751
00:39:31,719 --> 00:39:34,960
Speaker 3: I'm sure we all have, and it comes back to

752
00:39:35,080 --> 00:39:38,840
Speaker 3: exactly that lesson that depression is a kind of motivated state.

753
00:39:38,920 --> 00:39:41,680
Speaker 3: It's the brain is turning this on because it thinks

754
00:39:41,719 --> 00:39:43,759
Speaker 3: that it needs to be in this survival mechanism of

755
00:39:43,800 --> 00:39:46,000
Speaker 3: just folding and giving up. It thinks that that's its

756
00:39:46,000 --> 00:39:49,000
Speaker 3: best chance of survival. And so it's a highly motivated state.

757
00:39:49,040 --> 00:39:50,759
Speaker 3: And you will not be able to talk somebody out

758
00:39:50,800 --> 00:39:55,160
Speaker 3: of it because their motivational circuitry literally has been hijacked

759
00:39:55,200 --> 00:39:58,160
Speaker 3: by the depression, and so just talking people out of

760
00:39:58,160 --> 00:40:00,000
Speaker 3: it doesn't work terribly well. But as you say, now

761
00:40:00,000 --> 00:40:04,040
Speaker 3: now that we know where this motivational cerguit lives, now

762
00:40:04,040 --> 00:40:06,719
Speaker 3: that we know where this non reward circuit lives, we

763
00:40:06,760 --> 00:40:10,000
Speaker 3: can do all kinds of interventions. And you asked, what's

764
00:40:10,000 --> 00:40:11,839
Speaker 3: it going to look like in forty years. I don't

765
00:40:11,840 --> 00:40:15,600
Speaker 3: think there's going to be any one treatment that is

766
00:40:15,680 --> 00:40:18,760
Speaker 3: just universally what people use I'll give you an example

767
00:40:18,760 --> 00:40:21,160
Speaker 3: of that. So recently, a couple of years ago, a

768
00:40:21,200 --> 00:40:24,960
Speaker 3: team that you see San Francisco, led by Catherine Scangos

769
00:40:24,960 --> 00:40:27,839
Speaker 3: and colleagues. They were able to go to this non

770
00:40:27,880 --> 00:40:31,040
Speaker 3: reward circuit in the brain that I talked about, and

771
00:40:31,120 --> 00:40:33,319
Speaker 3: they took people who had very severe depression and they

772
00:40:33,320 --> 00:40:35,759
Speaker 3: did something that I think is very kind of futuristic.

773
00:40:36,239 --> 00:40:38,840
Speaker 3: First of all, they brought them into a special monitoring

774
00:40:39,160 --> 00:40:42,319
Speaker 3: ward in the hospital and they implanted little electrodes in

775
00:40:42,320 --> 00:40:44,200
Speaker 3: their brain and let them stay in the hospital for

776
00:40:44,239 --> 00:40:47,080
Speaker 3: several days or weeks. Normally, that's what you'll do in

777
00:40:47,160 --> 00:40:49,680
Speaker 3: epilepsy patients if you were trying to find the source

778
00:40:49,680 --> 00:40:51,880
Speaker 3: of the epilepsy within the brain. You'll put electrodes all

779
00:40:51,920 --> 00:40:53,400
Speaker 3: over the brain and you'll let them sit and you

780
00:40:53,400 --> 00:40:55,120
Speaker 3: wait for them to have seizures, and then you go

781
00:40:55,239 --> 00:40:57,480
Speaker 3: back and reconstruct where they came from so you can

782
00:40:57,520 --> 00:41:00,680
Speaker 3: perform a surgery. And this guy, they said, well, you

783
00:41:00,719 --> 00:41:03,080
Speaker 3: know the folks of depression, these folks are really depressed.

784
00:41:03,120 --> 00:41:06,120
Speaker 3: They can't function, their suicidal you know, they really need

785
00:41:06,120 --> 00:41:08,239
Speaker 3: something just as drastic as this. So they brought them in,

786
00:41:08,640 --> 00:41:11,000
Speaker 3: they implanted the electrodes but instead of waiting for seizures,

787
00:41:11,000 --> 00:41:13,440
Speaker 3: they just let them have negative thoughts and using a

788
00:41:13,440 --> 00:41:16,120
Speaker 3: little app on their tablet, they could constantly rate what

789
00:41:16,160 --> 00:41:19,000
Speaker 3: their brain was thinking about, and so you could see

790
00:41:19,080 --> 00:41:21,000
Speaker 3: what kind of brain activity was going on when they

791
00:41:21,040 --> 00:41:24,800
Speaker 3: were having positive thoughts or negative thoughts. And by doing

792
00:41:24,840 --> 00:41:27,320
Speaker 3: that and using a machine learning algorithm, they were able

793
00:41:27,320 --> 00:41:31,480
Speaker 3: to detect the electrodes that showed particular pattern of abnormal

794
00:41:31,520 --> 00:41:34,600
Speaker 3: activity that was present when the brain got sucked into

795
00:41:34,600 --> 00:41:37,440
Speaker 3: those negative ruminations. When they did that, they were then

796
00:41:37,480 --> 00:41:40,719
Speaker 3: able to implant a deep brain stimulator in that and

797
00:41:40,760 --> 00:41:42,880
Speaker 3: it was a closed loop system, so it was attached

798
00:41:42,880 --> 00:41:46,200
Speaker 3: to a tiny little computer that would that would detect

799
00:41:46,320 --> 00:41:49,000
Speaker 3: when the brain had gone into this abnormal rhythm of

800
00:41:49,040 --> 00:41:51,480
Speaker 3: negative thoughts and it would just disrupt the activity with

801
00:41:51,520 --> 00:41:53,520
Speaker 3: about five or six seconds of stimulation. So we just

802
00:41:53,520 --> 00:41:55,479
Speaker 3: flip thelip the lip, just to like when you tap

803
00:41:55,480 --> 00:41:57,440
Speaker 3: on a microphone to break a feedback loop. It was

804
00:41:57,480 --> 00:41:59,719
Speaker 3: literally just tapping on that microphone and saying, hey, stop it.

805
00:42:00,680 --> 00:42:02,759
Speaker 3: We've used this approach in the heart for a long time.

806
00:42:02,800 --> 00:42:06,279
Speaker 3: So people have heart rhythm problems, can wear things called implantable,

807
00:42:06,440 --> 00:42:09,839
Speaker 3: have a surgery to have an implantable a cardiac defibrillator,

808
00:42:10,000 --> 00:42:13,080
Speaker 3: so something like the defibrillator padals that you might see

809
00:42:13,080 --> 00:42:15,200
Speaker 3: in the airport, but this is actually implanted inside. So

810
00:42:15,239 --> 00:42:17,520
Speaker 3: if their heart ever gets stuck in an abnormal rhythm

811
00:42:17,760 --> 00:42:21,360
Speaker 3: that might be fatal, the device will automatically detect that

812
00:42:21,400 --> 00:42:23,239
Speaker 3: the heart's in that rhythm and just give a few

813
00:42:23,280 --> 00:42:26,680
Speaker 3: blips to reset it. So interestingly, they were doing the

814
00:42:26,680 --> 00:42:28,920
Speaker 3: same thing in the brain, these folks that effectively created

815
00:42:28,920 --> 00:42:32,480
Speaker 3: an implantable brain defibrillator, and so it was detecting when

816
00:42:32,520 --> 00:42:34,920
Speaker 3: this abnormal pattern comes along, they blip it for a

817
00:42:34,920 --> 00:42:35,600
Speaker 3: few seconds.

818
00:42:36,640 --> 00:42:37,160
Speaker 2: And there's a.

819
00:42:37,080 --> 00:42:38,719
Speaker 3: Lovely article in The New York Times a couple of

820
00:42:38,760 --> 00:42:40,759
Speaker 3: years ago where they interviewed the patient describe what it

821
00:42:40,840 --> 00:42:43,239
Speaker 3: was like, and they talked about it as being a

822
00:42:43,320 --> 00:42:45,600
Speaker 3: sort of you're about to get sucked down into these

823
00:42:45,640 --> 00:42:48,600
Speaker 3: negative thoughts, and she said, suddenly the rational side of

824
00:42:48,600 --> 00:42:51,680
Speaker 3: you comes on and those negative emotions can be separated

825
00:42:51,719 --> 00:42:55,080
Speaker 3: from your real situation. What was encouraging is that this

826
00:42:55,320 --> 00:42:58,319
Speaker 3: seems to this process of implanting these stimulators seems to

827
00:42:58,320 --> 00:43:01,200
Speaker 3: work even in people who've had depression for decades and

828
00:43:01,239 --> 00:43:05,239
Speaker 3: have tried every other treatment available, multiple medications therapies TMS,

829
00:43:05,280 --> 00:43:08,839
Speaker 3: even electric convulsive therapy, all kinds of things. So people

830
00:43:08,920 --> 00:43:11,880
Speaker 3: have really gotten nowhere with the other treatments using this

831
00:43:11,960 --> 00:43:15,239
Speaker 3: targeted intelligent approach. I think that really is sort of

832
00:43:15,239 --> 00:43:17,000
Speaker 3: the prototype of what the future looks like.

833
00:43:17,520 --> 00:43:19,640
Speaker 1: Yeah, I think one of the most amazing things about

834
00:43:19,640 --> 00:43:23,040
Speaker 1: this Many listeners will already sort of be aware of

835
00:43:23,080 --> 00:43:27,880
Speaker 1: this research, but generally we think of ourselves and our

836
00:43:27,920 --> 00:43:32,280
Speaker 1: personalities and our thoughts and our emotions as something different

837
00:43:32,440 --> 00:43:35,120
Speaker 1: from let's say our heart and how is our heart functioning,

838
00:43:35,160 --> 00:43:37,640
Speaker 1: And you can defibrillate the heart, but the brain it

839
00:43:37,680 --> 00:43:41,120
Speaker 1: feels like, well, that's me, that's just who I am,

840
00:43:41,160 --> 00:43:44,239
Speaker 1: and so on. And it's sort of an amazing revelation

841
00:43:44,480 --> 00:43:46,879
Speaker 1: that many people have when they start seeing this sort

842
00:43:46,880 --> 00:43:51,120
Speaker 1: of data to understand that we are physical creatures and

843
00:43:51,160 --> 00:43:55,360
Speaker 1: when you do things to change the physical structure, that

844
00:43:55,440 --> 00:43:57,040
Speaker 1: changes who you are in that moment.

845
00:43:58,320 --> 00:44:00,360
Speaker 3: I think that's spot on, And that comes back to

846
00:44:00,360 --> 00:44:02,279
Speaker 3: the story we told at the beginning of why it

847
00:44:02,320 --> 00:44:04,120
Speaker 3: was so interesting for me as a as a young

848
00:44:04,160 --> 00:44:08,000
Speaker 3: researcher that you know, at that time many years ago,

849
00:44:08,040 --> 00:44:10,640
Speaker 3: we really there were the default idea was this thing

850
00:44:10,680 --> 00:44:13,719
Speaker 3: called the serotonin bought. Thisis a depression where you know,

851
00:44:14,200 --> 00:44:16,319
Speaker 3: serotonin had something to do with your mood, and if

852
00:44:16,320 --> 00:44:18,360
Speaker 3: your mood was low, it was maybe because your serotonin

853
00:44:18,400 --> 00:44:20,360
Speaker 3: was low. You you know, didn't have enough serotonin in

854
00:44:20,400 --> 00:44:23,080
Speaker 3: your soup. So we should get out a serotonin shaker

855
00:44:23,080 --> 00:44:24,960
Speaker 3: and we should shake some put some more serotonin into

856
00:44:24,960 --> 00:44:26,880
Speaker 3: your soup, and that will somehow just you know, make

857
00:44:26,920 --> 00:44:29,839
Speaker 3: your mood get better. But it turns out, of course,

858
00:44:29,840 --> 00:44:32,520
Speaker 3: it's not as simple as that, the serotonin is not mood.

859
00:44:32,560 --> 00:44:35,760
Speaker 3: Serotonin in you know, in your in your GI tract

860
00:44:35,800 --> 00:44:38,239
Speaker 3: will will cause your you know, to have U to

861
00:44:38,400 --> 00:44:41,960
Speaker 3: have GI emotions in the brain, stomach can regulate nausea,

862
00:44:42,000 --> 00:44:44,080
Speaker 3: and the visual cortex it can do visual things. And

863
00:44:44,120 --> 00:44:47,279
Speaker 3: so there's no such thing as it really where mood

864
00:44:47,360 --> 00:44:49,160
Speaker 3: is just boiled down to not having enough of a

865
00:44:49,160 --> 00:44:52,560
Speaker 3: molecule in place. But when we looked at those cases,

866
00:44:52,600 --> 00:44:55,040
Speaker 3: as you said, where people who had been depressed for

867
00:44:55,080 --> 00:44:56,640
Speaker 3: so long that they thought it was just part of

868
00:44:56,680 --> 00:44:59,520
Speaker 3: who they were, they then have this experience where you

869
00:44:59,560 --> 00:45:03,080
Speaker 3: literally just take a circuit in the brain and blip

870
00:45:03,120 --> 00:45:06,359
Speaker 3: it and reset it, and the person immediately in their

871
00:45:06,360 --> 00:45:09,480
Speaker 3: thoughts is no longer getting stuck in the negative thoughts

872
00:45:09,480 --> 00:45:12,080
Speaker 3: and can look past the one thing that's going wrong

873
00:45:12,160 --> 00:45:13,960
Speaker 3: to the other ninety nine things that are going right

874
00:45:14,360 --> 00:45:17,200
Speaker 3: through that clear sort of logical way, And you're right,

875
00:45:17,239 --> 00:45:20,000
Speaker 3: people do really find it as a revelation, and people

876
00:45:20,040 --> 00:45:22,960
Speaker 3: who improve on these they often find that because they've

877
00:45:22,960 --> 00:45:26,080
Speaker 3: been depressed for twenty years, you know that they don't

878
00:45:26,360 --> 00:45:27,960
Speaker 3: It can be actually quite a lot of work to

879
00:45:28,000 --> 00:45:29,680
Speaker 3: sit down with a person and figure out how to

880
00:45:29,760 --> 00:45:32,680
Speaker 3: reconstruct their life based on the premise that they actually

881
00:45:32,719 --> 00:45:34,360
Speaker 3: get up every day and feel good and ready to

882
00:45:34,400 --> 00:45:37,120
Speaker 3: do things. They have spent twenty years building a life

883
00:45:37,120 --> 00:45:40,759
Speaker 3: around disability, so it's not something where so there often

884
00:45:40,760 --> 00:45:42,239
Speaker 3: can be quite a lot of work done over months

885
00:45:42,320 --> 00:45:44,280
Speaker 3: or years to try and figure out how the person

886
00:45:44,600 --> 00:45:46,480
Speaker 3: will adapt to a life that has hope in it.

887
00:45:46,520 --> 00:45:50,520
Speaker 1: Again, Yeah, so you once told me how you see

888
00:45:50,640 --> 00:45:54,319
Speaker 1: the battle against depression in the twenty first century from

889
00:45:54,320 --> 00:45:59,160
Speaker 1: a historical point of view. Yeah, so, I mean, let's

890
00:45:59,200 --> 00:46:01,480
Speaker 1: come back to those we talked about earlier on where

891
00:46:01,560 --> 00:46:04,759
Speaker 1: we said that there's the prevalence of depression over the

892
00:46:04,760 --> 00:46:07,279
Speaker 1: lifetime is maybe ten percent, and the prevalence at any

893
00:46:07,280 --> 00:46:08,680
Speaker 1: given time is about five percent.

894
00:46:09,239 --> 00:46:12,120
Speaker 3: Now. There are lots of diseases in the history of

895
00:46:12,120 --> 00:46:15,279
Speaker 3: medicine where the prevalence has come down a lot, So

896
00:46:15,400 --> 00:46:17,960
Speaker 3: people used to be a lot of people. Tuberculosis, that's

897
00:46:18,000 --> 00:46:20,920
Speaker 3: come down a lot, and we're now making progress against malaria.

898
00:46:20,960 --> 00:46:24,399
Speaker 3: We're making progress against various forms of hepatitis. We're making

899
00:46:24,440 --> 00:46:27,880
Speaker 3: progress against stomach alsers that used to sometimes be fatal

900
00:46:27,920 --> 00:46:29,719
Speaker 3: if they progress. And for each of these things we

901
00:46:29,760 --> 00:46:32,680
Speaker 3: now have effective treatments and the prevalence has come down.

902
00:46:32,719 --> 00:46:36,839
Speaker 3: Even for HIV, something that was once untreatable and uncontrollable

903
00:46:36,920 --> 00:46:39,239
Speaker 3: is now turned into something that is controllable, and that

904
00:46:39,320 --> 00:46:41,439
Speaker 3: over time we may be able to get the prevalences down.

905
00:46:42,320 --> 00:46:44,120
Speaker 3: So the dream for us, I think for the twenty

906
00:46:44,120 --> 00:46:46,440
Speaker 3: first century would be that we would like, you know,

907
00:46:46,880 --> 00:46:48,799
Speaker 3: at the end of our careers forty years from now,

908
00:46:48,800 --> 00:46:50,640
Speaker 3: as you said, we'd like to be able to look

909
00:46:50,680 --> 00:46:54,200
Speaker 3: back at the prevalence of depression and anxiety and other

910
00:46:54,320 --> 00:46:57,120
Speaker 3: mental health disorders and say, look at that we used

911
00:46:57,120 --> 00:46:59,000
Speaker 3: to be at five or ten percent, and look how

912
00:46:59,080 --> 00:47:02,680
Speaker 3: much numbers come down since then. Millions of people who

913
00:47:03,239 --> 00:47:07,000
Speaker 3: had no pathway forward now see. Depression is something that

914
00:47:07,080 --> 00:47:11,359
Speaker 3: is treatable, and employers no longer look at depression as

915
00:47:11,400 --> 00:47:14,040
Speaker 3: something that would disqualify you from being hired for a job.

916
00:47:14,400 --> 00:47:16,120
Speaker 3: Oh you have depression, that's okay, not the end of

917
00:47:16,160 --> 00:47:17,799
Speaker 3: the world. Just go in and get the course of

918
00:47:17,800 --> 00:47:19,440
Speaker 3: treatment and we'll see you. We'll see you back in

919
00:47:19,440 --> 00:47:22,120
Speaker 3: a week or two. So you know, this will help

920
00:47:22,160 --> 00:47:24,319
Speaker 3: to erode the stigma, and I think we'll really get

921
00:47:24,320 --> 00:47:26,600
Speaker 3: to see the numbers coming down on this. Are we

922
00:47:26,640 --> 00:47:28,799
Speaker 3: going to get those millions of people better with deep

923
00:47:28,800 --> 00:47:31,359
Speaker 3: brain stimulators alone? No, of course not. We're not going

924
00:47:31,400 --> 00:47:33,920
Speaker 3: to be implanting millions and millions of deep brain stimulators

925
00:47:33,960 --> 00:47:36,000
Speaker 3: and everybody, not everybody wants them and just throw our

926
00:47:36,120 --> 00:47:39,080
Speaker 3: up sersons to do that. But I think we do

927
00:47:39,160 --> 00:47:42,400
Speaker 3: have a real opportunity using the non invasive forms of

928
00:47:42,440 --> 00:47:46,040
Speaker 3: brain stimulation like TMS, which are getting you know, very

929
00:47:46,120 --> 00:47:49,719
Speaker 3: very good as well. So your colleague over at over

930
00:47:49,800 --> 00:47:52,360
Speaker 3: at Stanford are one of my good friends. Nolan Williams

931
00:47:52,719 --> 00:47:56,400
Speaker 3: was instrumental in developing a radical new form of TMS

932
00:47:56,440 --> 00:47:59,759
Speaker 3: treatment that could take a person from severe depression on

933
00:47:59,760 --> 00:48:01,920
Speaker 3: money day all the way down to being in remission

934
00:48:01,960 --> 00:48:06,040
Speaker 3: in literally five days. The secret was to do two things.

935
00:48:06,040 --> 00:48:07,880
Speaker 3: The verse was not to do a treatment once a

936
00:48:07,960 --> 00:48:11,200
Speaker 3: day traditionally, but to do up to ten treatments a day,

937
00:48:11,239 --> 00:48:12,840
Speaker 3: so that a person can have thirty or forty or

938
00:48:12,880 --> 00:48:15,720
Speaker 3: fifty treatments in a week and that's definitely enough TMS

939
00:48:15,719 --> 00:48:17,880
Speaker 3: sessions to get them better. The second part of their

940
00:48:17,880 --> 00:48:20,120
Speaker 3: trick was actually performed some brain imaging in the person

941
00:48:20,239 --> 00:48:22,319
Speaker 3: so you could see what pathways to be targeting and

942
00:48:22,360 --> 00:48:25,520
Speaker 3: then fine tune and personalized where the coil is. Through

943
00:48:26,320 --> 00:48:28,239
Speaker 3: some combination of those two things, they seem to be

944
00:48:28,320 --> 00:48:31,320
Speaker 3: hitting very high success rates that are north of fifty percent.

945
00:48:31,840 --> 00:48:35,040
Speaker 3: So we have a tool now with TMS that if

946
00:48:35,080 --> 00:48:38,440
Speaker 3: you know someone who has struggled with depression or anxiety

947
00:48:38,800 --> 00:48:41,399
Speaker 3: and has not done well on therapy or medications, that's

948
00:48:41,400 --> 00:48:43,680
Speaker 3: a lot of people. They can go anywhere in the

949
00:48:43,760 --> 00:48:46,239
Speaker 3: United States right now to a TMS clinic and they

950
00:48:46,239 --> 00:48:49,960
Speaker 3: can undergo a course of transcradial magnetic simulation. And with

951
00:48:50,520 --> 00:48:54,200
Speaker 3: the most recent FD protocols, we believe that we can

952
00:48:54,239 --> 00:48:56,359
Speaker 3: get more than fifty percent of people to remission even

953
00:48:56,400 --> 00:48:59,400
Speaker 3: if nothing else has worked. So we do think we

954
00:48:59,440 --> 00:49:02,080
Speaker 3: have a tool that is now capable of treating most

955
00:49:02,080 --> 00:49:04,960
Speaker 3: people with depression and getting at least half of them

956
00:49:05,120 --> 00:49:07,920
Speaker 3: out of depression, maybe more. The trick is going to

957
00:49:07,960 --> 00:49:10,279
Speaker 3: be to scale that. So it's scaling up so that

958
00:49:10,320 --> 00:49:12,400
Speaker 3: everyone in the country will have access to this treatment.

959
00:49:12,640 --> 00:49:16,440
Speaker 3: Once we're there, I think we will absolutely see improvements

960
00:49:16,520 --> 00:49:18,240
Speaker 3: in the prevalence in our lifetimes.

961
00:49:18,440 --> 00:49:22,080
Speaker 1: It's great, Hey, just dig into one more thing, because

962
00:49:22,120 --> 00:49:25,000
Speaker 1: you had talked. I've heard you talk before about tuberculosis

963
00:49:25,040 --> 00:49:26,960
Speaker 1: and the parallel there.

964
00:49:28,400 --> 00:49:32,239
Speaker 3: Yeah, so that's an interesting thing. It is possible. I

965
00:49:32,239 --> 00:49:34,319
Speaker 3: guess that our battle against depression in the twenty first

966
00:49:34,320 --> 00:49:36,880
Speaker 3: century is really a little bit like the battle against

967
00:49:37,080 --> 00:49:40,759
Speaker 3: tuberculosis in the nineteenth and the twentieth century. One of

968
00:49:40,760 --> 00:49:45,040
Speaker 3: the pioneers of modern medicine the nineteenth century physician Sir

969
00:49:45,080 --> 00:49:48,920
Speaker 3: William Osler. He, of course saw many patients in his

970
00:49:48,960 --> 00:49:51,839
Speaker 3: career with tuberculosis coming from the poorer areas of town,

971
00:49:51,920 --> 00:49:55,200
Speaker 3: the overcrowded areas and so on, the places where living

972
00:49:55,239 --> 00:49:58,360
Speaker 3: conditions were terrible, where sanitation was terrible, and as a result,

973
00:49:58,400 --> 00:50:03,360
Speaker 3: he described tuberculosis as is primarily quote a social disease

974
00:50:03,800 --> 00:50:06,719
Speaker 3: with a medical aspect. In other words, yes, we can

975
00:50:06,760 --> 00:50:09,759
Speaker 3: treat it medically, but Fundamentally, tuberculosis isn't going to go

976
00:50:09,800 --> 00:50:12,439
Speaker 3: away until people have better living conditions, until you don't

977
00:50:12,440 --> 00:50:15,120
Speaker 3: have eight people living in one room, until people aren't

978
00:50:15,160 --> 00:50:16,200
Speaker 3: with bad food, and all.

979
00:50:16,120 --> 00:50:16,560
Speaker 2: The rest of it.

980
00:50:16,640 --> 00:50:20,080
Speaker 3: So in fact, although tuberculosis drugs were developed in the

981
00:50:20,080 --> 00:50:23,000
Speaker 3: twentieth century and save millions of lives when they're invented,

982
00:50:23,480 --> 00:50:26,800
Speaker 3: the reality is that the rates of tuberculosis were coming

983
00:50:26,840 --> 00:50:29,960
Speaker 3: down decades before any of these drugs were ever ruled

984
00:50:30,000 --> 00:50:33,920
Speaker 3: out to reach people, and the prevalence of tuberculosis improved

985
00:50:33,920 --> 00:50:37,520
Speaker 3: because people's lives improved, you know, better food, cleaner water,

986
00:50:37,800 --> 00:50:43,040
Speaker 3: less crowded living conditions, less dire poverty, less desperation, And

987
00:50:43,200 --> 00:50:45,040
Speaker 3: I think we're going to see that a very similar

988
00:50:45,040 --> 00:50:46,480
Speaker 3: thing is happening here. It's not that we won't be

989
00:50:46,480 --> 00:50:49,399
Speaker 3: able to use new technologies like brain stimulation to pull

990
00:50:49,400 --> 00:50:52,120
Speaker 3: people out of despair, but it's also possible that a

991
00:50:52,200 --> 00:50:53,920
Speaker 3: key to getting people out of despair will be to

992
00:50:54,000 --> 00:50:57,640
Speaker 3: understand depression also as to some degree a social disease

993
00:50:57,680 --> 00:51:00,080
Speaker 3: with a medical aspect. If we go back to the

994
00:51:00,120 --> 00:51:02,640
Speaker 3: idea that depression is the thing that happens when the

995
00:51:02,640 --> 00:51:05,120
Speaker 3: brain has decided it's in a battle for survival that

996
00:51:05,160 --> 00:51:07,960
Speaker 3: it's not going to win. Then we look at the

997
00:51:07,960 --> 00:51:09,960
Speaker 3: prevalence of depression is a number of people who look

998
00:51:10,000 --> 00:51:12,480
Speaker 3: around at their lives and concluded that they are in

999
00:51:12,520 --> 00:51:16,160
Speaker 3: an unwinnable situation. And I believe in the same way

1000
00:51:16,200 --> 00:51:18,960
Speaker 3: that we part of the pathway to getting people out

1001
00:51:19,000 --> 00:51:22,200
Speaker 3: of depression and reducing its prevalence will be improving the

1002
00:51:22,200 --> 00:51:25,360
Speaker 3: conditions of people's lives. They're the degree to which they

1003
00:51:25,400 --> 00:51:27,160
Speaker 3: feel secure, a degree to which they don't feel like

1004
00:51:27,200 --> 00:51:29,200
Speaker 3: they're going to lose their housing or to be under

1005
00:51:29,239 --> 00:51:32,040
Speaker 3: threat of violence. The first places in the world to

1006
00:51:32,080 --> 00:51:35,960
Speaker 3: overcome depression will be the ones that don't just develop

1007
00:51:36,520 --> 00:51:40,320
Speaker 3: better technologies to reset the brain, but also develop stronger

1008
00:51:40,360 --> 00:51:43,839
Speaker 3: societies in which we just have fewer percentages of people

1009
00:51:43,880 --> 00:51:46,160
Speaker 3: who are trapped and fights for survival that they feel

1010
00:51:46,160 --> 00:51:49,800
Speaker 3: it can never seem to win. And I guess that's maybe.

1011
00:51:50,520 --> 00:51:54,000
Speaker 3: There is a concept which one of my colleagues introduced

1012
00:51:54,000 --> 00:51:56,160
Speaker 3: me to from the history of Judaism, and it's a

1013
00:51:56,200 --> 00:51:58,640
Speaker 3: lovely phrase that I guess really carry around with me

1014
00:51:58,800 --> 00:52:02,680
Speaker 3: all day. It's the phrase is to kun olam, and

1015
00:52:03,360 --> 00:52:05,600
Speaker 3: it has been described to me as a religious injunction

1016
00:52:05,760 --> 00:52:07,480
Speaker 3: to repair the world.

1017
00:52:08,120 --> 00:52:08,839
Speaker 2: Yeah I can't.

1018
00:52:09,000 --> 00:52:10,440
Speaker 3: I think you and I have also discussed this in

1019
00:52:10,440 --> 00:52:14,279
Speaker 3: the past as well. Yeah, so yeah, when we talk

1020
00:52:14,320 --> 00:52:16,640
Speaker 3: about resetting the brain, I think that falls within the

1021
00:52:16,719 --> 00:52:19,200
Speaker 3: larser of battles to try and improve the lot of

1022
00:52:19,280 --> 00:52:23,480
Speaker 3: humanity and reduce and reduce despair everywhere. And so when

1023
00:52:23,520 --> 00:52:26,560
Speaker 3: I think about the pathway to takun Olam and what

1024
00:52:26,760 --> 00:52:29,879
Speaker 3: neuroscience can contribute to it, and what you know brain

1025
00:52:29,920 --> 00:52:33,239
Speaker 3: stimulation can contribute to it, I think it has an

1026
00:52:33,360 --> 00:52:37,719
Speaker 3: essential role in reducing the number of people who face

1027
00:52:37,760 --> 00:52:39,800
Speaker 3: the world in despair, and that will be an essential

1028
00:52:39,840 --> 00:52:42,600
Speaker 3: component of this much larger injunction to repair the world,

1029
00:52:42,640 --> 00:52:44,000
Speaker 3: which I think we can all relate to.

1030
00:52:48,960 --> 00:52:52,600
Speaker 1: I spend many of these episodes talking about the extraordinary

1031
00:52:52,719 --> 00:52:56,520
Speaker 1: things that the brain does well, but it's equally important

1032
00:52:56,880 --> 00:52:59,799
Speaker 1: to talk about what happens when the brain gets off,

1033
00:53:00,760 --> 00:53:04,200
Speaker 1: because some percentage of your friends and loved ones are

1034
00:53:04,239 --> 00:53:07,680
Speaker 1: going to have to battle depression at some point, and

1035
00:53:07,719 --> 00:53:11,320
Speaker 1: it might be a slightly higher percentage than you think.

1036
00:53:11,920 --> 00:53:16,560
Speaker 1: The brain is incredible, but fragile, and what we see

1037
00:53:16,800 --> 00:53:20,480
Speaker 1: from depression is that it's relatively easy for it to

1038
00:53:20,680 --> 00:53:26,680
Speaker 1: slip out of its optimal operating range. Happily, neuroscience labs

1039
00:53:26,760 --> 00:53:30,600
Speaker 1: all over the world are working to understand this, and

1040
00:53:30,760 --> 00:53:36,279
Speaker 1: researchers and companies are generating new approaches, as with transcranial

1041
00:53:36,320 --> 00:53:41,439
Speaker 1: magnetic stimulation, such that as we move forward, we will

1042
00:53:41,440 --> 00:53:46,520
Speaker 1: have increasingly better ways to get things back on track.

1043
00:53:50,520 --> 00:53:53,840
Speaker 1: Go to Eagleman dot com slash podcast for more information

1044
00:53:53,960 --> 00:53:57,200
Speaker 1: and to find further reading. Send me an email at

1045
00:53:57,280 --> 00:54:00,799
Speaker 1: podcasts at eagleman dot com with questions or discus, and

1046
00:54:00,880 --> 00:54:03,520
Speaker 1: I'll be making monthly episodes in which I address those

1047
00:54:04,520 --> 00:54:07,920
Speaker 1: and check out and subscribe to Inner Cosmos on YouTube

1048
00:54:08,000 --> 00:54:11,560
Speaker 1: for videos of each episode and to leave comments until

1049
00:54:11,560 --> 00:54:15,480
Speaker 1: next time. I'm David Eagleman, and this is Inner Cosmos.