Ep 48: Why do brains become depressed? | INNER COSMOS WITH DAVID EAGLEMAN

00:53:52
https://www.youtube.com/watch?v=Yf0cTXbfkvQ

概要

TLDRNeste episódio de "Inner Cosmos", David Eagleman, neurocientista e autor, examina a depressão, suas causas e efeitos, ao lado de novas abordagens para seu tratamento. Eagleman discute como o estado mental relacionado à depressão não é apenas um problema emocional, mas também físico, relacionado a alterações específicas no cérebro. Ele explora a ideia de que a depressão é uma resposta evolutiva a ameaças irreversíveis e como essa resposta pode se tornar uma armadilha mental. Eagleman entrevista especialistas que detalham experimentos, como o uso de estimuladores cerebrais para aliviar sintomas de Parkinson, que inesperadamente evidenciaram a relação entre estímulos cerebrais e sintomas de depressão. É discutido o uso inovador de tecnologias como a estimulação magnética transcraniana (TMS) e dispositivos implantáveis que prometem novas esperanças para aqueles que não respondem bem a medicamentos tradicionais. Há uma ênfase em entender a depressão não apenas como uma doença social, mas uma com raízes biológicas concretas e como intervenções tecnológicas podem revolucionar seu tratamento.

収穫

  • 🧠 A depressão envolve mudanças específicas no funcionamento cerebral.
  • 🐶 Sintomas de depressão podem ser observados em vários animais.
  • ⚖️ Equilíbrio químico cerebral é crucial para evitar a depressão.
  • 💊 Medicamentos nem sempre são eficazes para todos os pacientes.
  • 🔦 Novas opções de tratamento como TMS estão sendo exploradas.
  • 🧬 A depressão é tanto um problema social como biológico.
  • ✨ TMS é promissor devido à sua precisão não invasiva.
  • 🔁 A neuroplasticidade tem papel central no tratamento da depressão.
  • 🧩 Intervenções tecnológicas podem oferecer novas soluções.
  • 🔍 Compreender a depressão a partir de múltiplas perspectivas é essencial.

タイムライン

  • 00:00:00 - 00:05:00

    David Eagleman investiga a depressão, focando na facilidade do cérebro em escorregar para essa condição. Ele explica que a depressão é um problema físico, semelhante a doenças físicas como a COVID-19. O cérebro é composto por pequenas peças e qualquer alteração pode alterar o humor e comportamento de uma pessoa.

  • 00:05:00 - 00:10:00

    Danos sutis ao cérebro, que não são visíveis externamente, podem alterar seu funcionamento. Eagleman compara isso a um bloco da cidade de Nova York que caiu. Ele conversa com Jonathan Downer, um especialista, para entender como esses pequenos ajustes cerebrais impactam a depressão.

  • 00:10:00 - 00:15:00

    Downer compartilha um caso de estudo em que a estimulação cerebral profunda alterou rapidamente o humor de uma paciente com depressão. A pesquisa sugere que a depressão pode estar ligada a padrões específicos de atividade no cérebro, fornecendo insights valiosos sobre novos tratamentos.

  • 00:15:00 - 00:20:00

    Downer explica a depressão como um mecanismo de defesa cerebral contra ameaças invencíveis, semelhante ao comportamento de animais em situações de perigo. Essa perspectiva é um ponto de partida para novas abordagens de tratamento.

  • 00:20:00 - 00:25:00

    David e Jonathan discutem o aumento da depressão e possíveis razões sociais, psicológicas e biológicas. A incidência crescente sugere desafios contínuos na saúde mental e a necessidade de novos tratamentos.

  • 00:25:00 - 00:30:00

    Os tratamentos farmacêuticos para depressão, embora úteis, não são 100% eficazes, com muitos pacientes não respondendo aos medicamentos tradicionais. Discussões sobre novas abordagens, como a estimulação cerebral, se mostram promissoras.

  • 00:30:00 - 00:35:00

    Jonathan discute recentes avanços na compreensão cerebral e tratamentos, como a estimulação magnética transcraniana. Eles estão mapeando circuitos cerebrais associados a transtornos mentais, oferecendo novos caminhos terapêuticos.

  • 00:35:00 - 00:40:00

    Estudos explicam como a depressão afeta as simulações futuras do cérebro, focando em resultados negativos. Intervenções cerebrais visam liberar circuitos presos, expandindo a plasticidade cerebral para novos padrões.

  • 00:40:00 - 00:45:00

    Tratamentos avançados visam reconfigurar a plasticidade cerebral, quebrando loops de ruminação negativa. Essa estratégia mostra como novos tratamentos podem alterar o curso da depressão.

  • 00:45:00 - 00:53:52

    O futuro do tratamento da depressão pode envolver uma combinação de avanços médicos e melhorias nas condições sociais. A abordagem colaborativa poderia reduzir significativamente a prevalência de depressão, assim como ocorreu com outras doenças no passado.

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よくある質問

  • Quem é David Eagleman?

    David Eagleman é um neurocientista e autor, conhecido por explorar diversos aspectos do cérebro e suas funções.

  • O que é depressão?

    Depressão é um transtorno de humor que afeta como a pessoa se sente, pensa e lida com atividades diárias, muitas vezes resultando em sentimentos persistentes de tristeza e desesperança.

  • A depressão é detectável em animais?

    Sim, sinais de depressão podem ser observados em animais como cães, gatos, elefantes e até peixes-zebra.

  • Como o cérebro entra em estado de depressão?

    O cérebro pode entrar em depressão devido a desequilíbrios químicos e mudanças na atividade cerebral, muitas vezes resultando em uma resposta de defesa passiva a ameaças.

  • Que tratamentos farmacêuticos para depressão estão disponíveis?

    Existem medicamentos que aumentam os níveis de serotonina, norepinefrina ou dopamina, mas eles não funcionam para todos e podem ter efeitos colaterais.

  • O que é estimulação magnética transcraniana (TMS)?

    TMS é um tratamento que usa pulsos magnéticos para estimular áreas específicas do cérebro, ajudando a aliviar os sintomas de depressão.

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  • 00:00:00
    what is depression and why are brains so
  • 00:00:03
    easily able to slip into it is
  • 00:00:06
    depression detectable in animals and
  • 00:00:09
    when we look across the animal kingdom
  • 00:00:11
    do we see options Beyond fight or flight
  • 00:00:15
    and what is any of this have to do with
  • 00:00:17
    measuring depression medications in City
  • 00:00:20
    Water Supplies or reward Pathways in the
  • 00:00:23
    brain or the prevalence of tuberculosis
  • 00:00:26
    or zapping the head with magnetic
  • 00:00:28
    stimulation
  • 00:00:32
    welcome to Inner Cosmos with me David
  • 00:00:34
    Eagleman I'm a neuroscientist and an
  • 00:00:36
    author at Stanford and in these episodes
  • 00:00:39
    we sail deeply into our three pound
  • 00:00:41
    Universe to understand why and how our
  • 00:00:45
    lives look the way they
  • 00:00:46
    [Laughter]
  • 00:00:54
    do today's episode is about depression
  • 00:00:58
    we are going to dive into the science
  • 00:01:01
    behind it and we'll see what new
  • 00:01:03
    Solutions are on the horizon so let me
  • 00:01:06
    start by zooming way out what fascinates
  • 00:01:09
    me is not just what the brain can
  • 00:01:12
    accomplish in terms of our normal
  • 00:01:14
    functioning but also one can't help but
  • 00:01:17
    notice the fragility of the brain I mean
  • 00:01:20
    just think about how easy it is to lose
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    Consciousness when you hit your head or
  • 00:01:26
    think about what happens when you drink
  • 00:01:29
    alcohol and your perception and your
  • 00:01:31
    decision-making changes or you don't get
  • 00:01:34
    enough sleep and how you behave and how
  • 00:01:36
    you decide these can become a little
  • 00:01:38
    different or when you're hangry and you
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    act differently or if you consume
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    psychedelic drugs and your conscious
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    experience changes entirely what all
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    this tells us I think is that it's very
  • 00:01:51
    easy for the system to get knocked off
  • 00:01:53
    its normal pathway and what's clear is
  • 00:01:56
    that the brain puts an enormous amount
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    of effort into trying to stay operating
  • 00:02:02
    in the normal
  • 00:02:04
    range now given this context one area
  • 00:02:08
    that's fascinating and of massive social
  • 00:02:11
    importance is depression this is a mood
  • 00:02:15
    disorder it affects how you feel how you
  • 00:02:18
    think how you handle your daily tasks
  • 00:02:21
    how you eat and sleep people with
  • 00:02:23
    depression feel persistently sad they
  • 00:02:27
    often feel empty or
  • 00:02:30
    anxious pessimistic hopeless worthless
  • 00:02:34
    helpless and they lose interest in the
  • 00:02:37
    things that used to bring them Joy they
  • 00:02:40
    are slowed down in all the aspects of
  • 00:02:42
    their life and often there are thoughts
  • 00:02:45
    of suicide now almost everyone has had
  • 00:02:49
    someone in their life who has suffered
  • 00:02:51
    depression at some point whether that's
  • 00:02:53
    recognized or not and generally
  • 00:02:56
    everyone's first intuition when they
  • 00:02:59
    have a friend or a loved one who becomes
  • 00:03:01
    depressed is to talk them out of it to
  • 00:03:04
    say hey things are okay snap out of it
  • 00:03:08
    look at the bright side and eventually
  • 00:03:10
    you might be tempted to say come on just
  • 00:03:13
    toughen up but the important lesson from
  • 00:03:16
    centuries of Psychiatry and more
  • 00:03:18
    recently Neuroscience is that it's not
  • 00:03:21
    so easy it's a physical problem and
  • 00:03:24
    that's why we talk about mental illness
  • 00:03:27
    nowadays exactly as we talk about a
  • 00:03:29
    physical illness like covid or a broken
  • 00:03:32
    leg and that understanding opens the
  • 00:03:36
    door to different approaches because a
  • 00:03:39
    physical problem invites physical
  • 00:03:43
    Solutions now my father was a
  • 00:03:46
    psychiatrist and he was always impressed
  • 00:03:48
    that he could have a patient who would
  • 00:03:51
    be suffering from clinical depression
  • 00:03:53
    and would lose his job and maybe lose
  • 00:03:56
    his spouse and my father could make a
  • 00:03:57
    prescription like let's say Prozac and
  • 00:04:01
    that patient often could get out of bed
  • 00:04:03
    again and then get his job back and win
  • 00:04:06
    his spouse back now how do we understand
  • 00:04:09
    this well it's an issue that I talk
  • 00:04:11
    about a lot which is that we are made up
  • 00:04:14
    of small pieces and parts and the thing
  • 00:04:17
    to appreciate is that you are the sum
  • 00:04:20
    total of all those pieces and parts
  • 00:04:22
    whatever is going on at this microscopic
  • 00:04:24
    level is you and your mood and your
  • 00:04:28
    behavior now why would anybody think
  • 00:04:31
    that crazy statement is true well there
  • 00:04:33
    are many things that we see in the
  • 00:04:35
    clinics every day which teach us this
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    lesson people can get damaged to their
  • 00:04:41
    brains and they can no longer understand
  • 00:04:43
    how to use a mirror or they can no
  • 00:04:46
    longer name furry animals or they can no
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    longer see colors or understand speech
  • 00:04:53
    or understand music or any of a million
  • 00:04:56
    other things that we think should just
  • 00:04:58
    come for free in the world world now
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    what this exposes is that these are
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    functions of the brain and even if a
  • 00:05:05
    little bit of the brain is damaged then
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    you can't perform that function anymore
  • 00:05:11
    now many of the sorts of brain damage
  • 00:05:13
    that you'll read about in an exciting
  • 00:05:16
    book about the brain these are things
  • 00:05:17
    that most people won't see in their
  • 00:05:20
    lifetimes they won't know any friend or
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    relative who has these issues because
  • 00:05:25
    they are rare things to happen and they
  • 00:05:28
    usually involve Dam Dage to a region of
  • 00:05:31
    the brain from a tumor or a stroke or a
  • 00:05:33
    traumatic brain injury and those things
  • 00:05:36
    represent big changes in the city of the
  • 00:05:39
    brain like an entire block of New York
  • 00:05:41
    City falling in an earthquake but there
  • 00:05:44
    are much more subtle things that happen
  • 00:05:46
    in the brain as well and these are
  • 00:05:48
    changes that have to do with the way the
  • 00:05:51
    system runs with its tens of billions of
  • 00:05:54
    neurons and trillions of synaptic
  • 00:05:57
    connections so to return to the City
  • 00:05:59
    analogy imagine that instead of big
  • 00:06:01
    damage that you can see the city still
  • 00:06:05
    looks the same but parts of it are
  • 00:06:07
    operating very subtly differently so the
  • 00:06:11
    playwrights have all quit and the city
  • 00:06:14
    planners have stopped planning and the
  • 00:06:17
    coffee shops are closing 2 hours earlier
  • 00:06:20
    and all of this stuff impedes the city's
  • 00:06:23
    ability to thrive and be an active
  • 00:06:27
    well-functioning place for Innovation
  • 00:06:29
    and tourism but it's all very subtle and
  • 00:06:32
    if you looked at this from a drone
  • 00:06:34
    flying over the city you really wouldn't
  • 00:06:36
    see much of a difference it's small
  • 00:06:39
    stuff that's happening at a small level
  • 00:06:42
    but it changes the way that the city
  • 00:06:46
    operates and again who you are and how
  • 00:06:49
    you see the world comes from the way
  • 00:06:52
    that the city of your brain is operating
  • 00:06:55
    in other words the sum total of what's
  • 00:06:57
    Happening under the hood your
  • 00:07:00
    biology and I think the reason this is
  • 00:07:02
    surprising is because we tend to think
  • 00:07:05
    of ourselves as being removed from our
  • 00:07:09
    biology or separate from it or able to
  • 00:07:12
    ride above
  • 00:07:14
    it so if you've ever known someone with
  • 00:07:17
    depression or had depression yourself
  • 00:07:19
    you will know that you can't just say
  • 00:07:22
    hey come on cheer up snap out a bit that
  • 00:07:25
    doesn't suffice to change the
  • 00:07:28
    biology
  • 00:07:30
    and one of the most pervasive and
  • 00:07:32
    Society important examples of these kind
  • 00:07:36
    of subtle changes to the brain is with
  • 00:07:39
    depression and so for this episode I
  • 00:07:42
    decided to call my colleague Jonathan
  • 00:07:43
    Downer who is an incredibly insightful
  • 00:07:47
    and empathic Observer of the brain he
  • 00:07:50
    has an MD and specializes in Psychiatry
  • 00:07:53
    and he also has a PHD in neuroscience
  • 00:07:56
    and one of his areas of expertise is
  • 00:07:58
    depression and as it turns out Jonathan
  • 00:08:01
    and I wrote a textbook together on
  • 00:08:03
    cognitive Neuroscience called brain and
  • 00:08:05
    behavior and this is the textbook used
  • 00:08:08
    at Stanford and at universities
  • 00:08:10
    worldwide and the textbook covers a lot
  • 00:08:12
    of ground but for today I just want to
  • 00:08:15
    zoom in on depression so I rang him up
  • 00:08:18
    to get his perspective on this issue
  • 00:08:21
    that is not only neuroscientifically
  • 00:08:23
    important and fascinating but also
  • 00:08:27
    unlike the strange deficits that you
  • 00:08:28
    might see only in a textbook you almost
  • 00:08:31
    certainly know someone with depression
  • 00:08:33
    perhaps someone close to you or perhaps
  • 00:08:35
    yourself it's a shockingly common
  • 00:08:39
    challenge so let's dive in to understand
  • 00:08:46
    it so Jonathan how did you get
  • 00:08:48
    interested in studying
  • 00:08:50
    depression well it's a a bit of an
  • 00:08:52
    interesting story David um you'd have to
  • 00:08:54
    go back about 20 years to when I was a
  • 00:08:57
    graduate student over at the Toronto
  • 00:08:59
    Western Hospital that is a hospital that
  • 00:09:01
    has a uh I guess a major Neurosurgical
  • 00:09:04
    unit where they perform surgeries where
  • 00:09:07
    they implant deep brain stimulators uh
  • 00:09:09
    which are a bit like brain pacemakers
  • 00:09:11
    into the brains of people with
  • 00:09:13
    Parkinson's disease and other kinds of
  • 00:09:14
    neurological disorders uh and around
  • 00:09:17
    2002 a patient came in uh who was a
  • 00:09:20
    middle-aged woman who had previously
  • 00:09:22
    suffered from depression but no longer
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    and she was coming in to have the deep
  • 00:09:25
    brain simulators implanted for her
  • 00:09:27
    Parkinson's disease they imp the
  • 00:09:29
    electrodes one on one side and one on
  • 00:09:31
    the other and uh during the surgery they
  • 00:09:33
    turned them on to make sure that they
  • 00:09:35
    are succeeding in reducing the person's
  • 00:09:37
    hand tremors or the other Tremors in
  • 00:09:39
    their body that uh that they're trying
  • 00:09:41
    to have treated what was interesting is
  • 00:09:43
    when they turned on the one on one side
  • 00:09:45
    the opposite hand started to reduce in
  • 00:09:48
    its Tremor and the Tremor went away
  • 00:09:49
    which is exactly what they expected to
  • 00:09:51
    happen on the other side though
  • 00:09:53
    something very strange happened as soon
  • 00:09:54
    as they turned it on nothing happened to
  • 00:09:56
    her Tremor whatsoever and instead she
  • 00:09:58
    descended instantly into a deep
  • 00:10:02
    despairing reexperiencing of her
  • 00:10:05
    depression it kicked in within seconds
  • 00:10:07
    and she described it as a deep down bad
  • 00:10:09
    feeling in the pit of my stomach I
  • 00:10:11
    wanted to cry but I couldn't uh someone
  • 00:10:14
    could have come in to shoot me and I
  • 00:10:15
    wouldn't have cared I couldn't have
  • 00:10:16
    cared less now immediately they turned
  • 00:10:19
    the switch off again and surprisingly
  • 00:10:21
    within seconds the sadness lifted again
  • 00:10:24
    and they found themselves in a very
  • 00:10:26
    weird situation where every time they
  • 00:10:27
    turned on this current the person would
  • 00:10:30
    descend immediately within a few seconds
  • 00:10:32
    into sadness and then every time they
  • 00:10:33
    turned it off she would be able to
  • 00:10:35
    emerge within a few seconds again it was
  • 00:10:37
    literally sadness of the flip of a
  • 00:10:40
    switch wow and so that's what got you
  • 00:10:42
    started in researching that so that's
  • 00:10:45
    exactly it so at the time I was doing my
  • 00:10:48
    PhD using a technology called functional
  • 00:10:51
    functional MRI which I'm sure you've
  • 00:10:52
    talked about uh on on the podcast before
  • 00:10:55
    which is a way of using MRI scanners to
  • 00:10:57
    look at the brain activity of people as
  • 00:10:59
    various things happen so the
  • 00:11:01
    neurosurgeons wanted to understand what
  • 00:11:03
    was going on so we went down to where
  • 00:11:05
    the functional MRIs were being done and
  • 00:11:07
    uh they turned on and off one of the
  • 00:11:10
    switches on the one side that affected
  • 00:11:11
    the Tremor and they were able to show a
  • 00:11:13
    particular brain pathway that was
  • 00:11:14
    affected controlling the motor circuits
  • 00:11:16
    of the brain which is the intended
  • 00:11:18
    effect on the other hemisphere though
  • 00:11:20
    the electrode was just a few millimeters
  • 00:11:22
    off and as a resulted it landed on some
  • 00:11:24
    other Pathways that projected out to a
  • 00:11:26
    completely different part of the frontal
  • 00:11:28
    loopes and every time they turned on and
  • 00:11:30
    off this part of the frontal loopes the
  • 00:11:31
    person would instantly go in and out of
  • 00:11:33
    the sadness now that was happy news for
  • 00:11:35
    the patient because they were able to
  • 00:11:36
    reposition the electrodes so that both
  • 00:11:38
    electrodes did the appropriate thing but
  • 00:11:40
    it got us thinking about what this
  • 00:11:43
    really meant about depression um all
  • 00:11:45
    these theories at the time that
  • 00:11:46
    depression might be a chemical imbalance
  • 00:11:48
    or this or that uh we really saw very
  • 00:11:50
    directly that there was a question of
  • 00:11:52
    the activity of the brain and that
  • 00:11:53
    within seconds one pattern of activity
  • 00:11:55
    in the brain led to sadness and within
  • 00:11:57
    seconds if that pattern of activity
  • 00:11:59
    could somehow be turned off then the
  • 00:12:01
    person's sadness would go away and that
  • 00:12:03
    really got us thinking about whether we
  • 00:12:05
    might start being able to use things
  • 00:12:06
    like brain stimulation to understand
  • 00:12:09
    what uh Depression was about in the
  • 00:12:10
    brain and maybe even to come up with a
  • 00:12:12
    new generation of treatments that work
  • 00:12:13
    better than the medications and therapy
  • 00:12:15
    of the time okay terrific so we'll talk
  • 00:12:18
    about that um let's start with can you
  • 00:12:20
    define depression clinical depression
  • 00:12:23
    sure um so there are standardized
  • 00:12:25
    definitions of depression that involve a
  • 00:12:27
    series of symptoms the core of which is
  • 00:12:29
    sad or depressed mood most of the day
  • 00:12:31
    most days and the second of which is a
  • 00:12:33
    thing called anhedonia which is the
  • 00:12:35
    inability to enjoy things or experience
  • 00:12:37
    pleasure a loss of motivation a loss of
  • 00:12:39
    Joy a loss of the brain's reward
  • 00:12:41
    functions uh in addition to that there
  • 00:12:43
    are some standard symptoms that go along
  • 00:12:45
    with that commonly people will have
  • 00:12:47
    disturbances in their sleep or appetite
  • 00:12:49
    trouble with concentration uh they may
  • 00:12:51
    have difficulty with their energy and
  • 00:12:53
    fatigue levels uh and there are thoughts
  • 00:12:55
    that come along of self harm and suicide
  • 00:12:57
    that are that are obviously the most
  • 00:12:58
    concerning Parts uh about the depression
  • 00:13:01
    so that's the standard sort of
  • 00:13:02
    diagnostic approach by which we
  • 00:13:04
    determine whether somebody has been
  • 00:13:06
    entering into a a period of depression
  • 00:13:08
    it's unfortunately really common at any
  • 00:13:10
    given time in North America about 5% of
  • 00:13:13
    people uh are in the middle of a
  • 00:13:15
    depressive episode and at least 10% of
  • 00:13:17
    people perhaps more these days are going
  • 00:13:19
    to go through an episode of depression
  • 00:13:21
    at some point in their lifetimes almost
  • 00:13:23
    everybody will have somebody they know
  • 00:13:26
    who has been through depression or is
  • 00:13:27
    going through depression or will go
  • 00:13:29
    through depression so one of the things
  • 00:13:31
    I want to talk about is why this happens
  • 00:13:33
    what it is about the wiring of the human
  • 00:13:35
    brain that allows us to slip so easily
  • 00:13:38
    into that mode what are your thoughts on
  • 00:13:41
    that it's it's a really fascinating
  • 00:13:43
    question uh and I think to answer that
  • 00:13:46
    what we found is you can get a lot of
  • 00:13:48
    the clue to that looking at Evolution or
  • 00:13:50
    biology um because humans are not by no
  • 00:13:52
    means the only animals that can go into
  • 00:13:54
    a dispair like syndrome I mean
  • 00:13:55
    depression most of us who have pets and
  • 00:13:57
    most of us have animals who have seen
  • 00:13:58
    seen uh situations where animals can
  • 00:14:01
    drop into a Despair and stop eating and
  • 00:14:03
    stop sleeping and do all the same things
  • 00:14:04
    and don't enjoy the things they normally
  • 00:14:06
    would uh something that looks a bit like
  • 00:14:08
    depression is is detectable in dogs and
  • 00:14:10
    cats and elephants and zoo animals and
  • 00:14:13
    even even in things like zebra fish
  • 00:14:15
    which are you know tiny little
  • 00:14:16
    vertebrates so Evolution seems to have
  • 00:14:19
    put a depression-like mode there you
  • 00:14:21
    know a very long time ago and it's one
  • 00:14:23
    of the oldest circuits in the brain when
  • 00:14:26
    we look at the circuitry that drives
  • 00:14:27
    depression what we find is it falls into
  • 00:14:29
    a bigger category of circuits that help
  • 00:14:32
    the brain to defend against threats uh
  • 00:14:34
    and in a nutshell for every living thing
  • 00:14:36
    whether you're a fish or a raccoon or a
  • 00:14:38
    human there are sort of four main
  • 00:14:40
    categories of things you can do if a
  • 00:14:42
    threat comes along so let's say you're a
  • 00:14:43
    fish swimming along and and a shark
  • 00:14:45
    shows up the first thing you can do is
  • 00:14:47
    you can freeze and hope the shark
  • 00:14:49
    doesn't see you so that's freeze mode if
  • 00:14:51
    the shark sees you and starts chasing
  • 00:14:52
    you then you have to go beyond freeze
  • 00:14:53
    you have to go into the sort of the
  • 00:14:54
    flight mode which would be the Escape
  • 00:14:56
    mode uh and if the shark Corners you uh
  • 00:14:59
    we've all seen that there animals you
  • 00:15:01
    know if you happen to get a psum or a
  • 00:15:02
    raccoon in your garage um they usually
  • 00:15:05
    will run away but of course if they get
  • 00:15:06
    cornered and they feel like there's no
  • 00:15:07
    way out they will fight very fiercely
  • 00:15:09
    and lots of animals do that so there is
  • 00:15:12
    this third Mode called fight but the
  • 00:15:14
    brain needs a fourth mode to deal with
  • 00:15:16
    situations that are unwinable sometimes
  • 00:15:18
    you've tried freezing you've tried
  • 00:15:20
    fleeing you've tried fighting but if at
  • 00:15:22
    some point the brain decides you're not
  • 00:15:23
    going to win this fight and there's no
  • 00:15:24
    running away there's no escaping and you
  • 00:15:26
    can't just ignore the problem the brain
  • 00:15:28
    Taps into a fourth mode that I'll call
  • 00:15:30
    fold it's a passive threat defense mode
  • 00:15:33
    where the instincts are all about losing
  • 00:15:35
    your confidence running home and hiding
  • 00:15:37
    in your burrow and keeping your head
  • 00:15:38
    down and hoping that something changes
  • 00:15:41
    this is the mode that is turned on when
  • 00:15:43
    people are fighting off an illness or a
  • 00:15:45
    major injury so if they have surgery or
  • 00:15:46
    if they're fighting off an illness some
  • 00:15:48
    people will actually have a drop in
  • 00:15:49
    their mood when they have an
  • 00:15:50
    immunization as their immune system
  • 00:15:52
    fires up to sort of to deal with the
  • 00:15:54
    infection um but in any situation where
  • 00:15:56
    the brain decides that it needs to be
  • 00:15:58
    hiding doubt in recovery and recovering
  • 00:16:01
    and keeping its head down it will go
  • 00:16:03
    into this fold mode um now that may be
  • 00:16:06
    necessary to keep you out of danger uh
  • 00:16:09
    until the threat goes away or at least
  • 00:16:10
    hopefully until the threat goes away but
  • 00:16:12
    the problem that comes up in depression
  • 00:16:14
    is when this becomes a self-perpetuating
  • 00:16:16
    process and the circuits that drive fold
  • 00:16:19
    mode which is a normal and useful
  • 00:16:21
    defense mechanism for the threats we
  • 00:16:23
    can't win against if those circuits get
  • 00:16:25
    stuck in in an infinite feedback loop
  • 00:16:26
    and just keep going and going then the
  • 00:16:28
    person may still be stuck in depression
  • 00:16:30
    Weeks Later months later maybe even
  • 00:16:32
    years later you once gave me an example
  • 00:16:34
    of uh falling off a ship in the middle
  • 00:16:37
    of the night to illustrate this fold
  • 00:16:39
    mode yeah so I want that's actually a
  • 00:16:41
    great Point um so there are situations
  • 00:16:44
    where you we're we're doing we're going
  • 00:16:46
    into this mode is really useful and uh
  • 00:16:48
    the every once in a while we're reading
  • 00:16:50
    the news about somebody who falls off
  • 00:16:51
    the back of a ship in the middle of the
  • 00:16:53
    night and then miraculously gets rescued
  • 00:16:55
    in the morning now if you or I fell off
  • 00:16:57
    the back of a ship in the middle of the
  • 00:16:58
    night like a cruise ship or something
  • 00:16:59
    we'd probably swim after the ship for a
  • 00:17:01
    while and scream for help and try and
  • 00:17:03
    attract his attention but if it was
  • 00:17:04
    really clear that the ship was sailing
  • 00:17:06
    away and no one could hear us and we
  • 00:17:07
    were stuck in the middle of the sea I
  • 00:17:10
    mean we're in a really bad situation
  • 00:17:11
    it's really risky and this is probably
  • 00:17:12
    not going to work out well but our best
  • 00:17:14
    chance of survival is actually to to
  • 00:17:17
    fold to curl up into a ball and just
  • 00:17:20
    wait and save your energy and hope that
  • 00:17:22
    something about the situation changes
  • 00:17:24
    hope you get rescued that mode is the
  • 00:17:26
    same mode that we talk about when we
  • 00:17:28
    talk about depression and in fact when
  • 00:17:31
    pharmaceutical companies are developing
  • 00:17:32
    new medications for depression one of
  • 00:17:34
    the ways that they'll do animal testing
  • 00:17:36
    to see if the molecule help suppression
  • 00:17:38
    is with the thing called the forced swim
  • 00:17:39
    test in the forc swim test the animal
  • 00:17:42
    like the mouse or whatever uh is placed
  • 00:17:44
    inside an air a little Beaker where they
  • 00:17:46
    have to swim around and there's nothing
  • 00:17:48
    to stand on now mice are quite good
  • 00:17:49
    swimmers and they're also quite good
  • 00:17:50
    floaters so they'll swim and swim around
  • 00:17:53
    and eventually at some point they'll
  • 00:17:54
    realize that they're not going to get
  • 00:17:55
    out of this situation and so they stop
  • 00:17:57
    swimming around and they just give up
  • 00:17:58
    and float uh and at that point the
  • 00:18:00
    experiment will stop the stopwatch and
  • 00:18:02
    see how many minutes that took what's
  • 00:18:04
    interesting is that uh there are breeds
  • 00:18:07
    of mice who are prone to depression and
  • 00:18:08
    prone to sort of giving up quickly um
  • 00:18:11
    and most anti-depressants when the mice
  • 00:18:13
    are on the antidepressant they'll
  • 00:18:14
    actually swim for a lot longer before
  • 00:18:16
    giving up and so this Force swim test uh
  • 00:18:19
    which is really just a way of tapping
  • 00:18:20
    into how long before the animal switches
  • 00:18:22
    into this mode of folding and giving up
  • 00:18:24
    and waiting for something to change um
  • 00:18:27
    that approach is a a long-standing and
  • 00:18:30
    standard way that people have searched
  • 00:18:31
    for uh new anti-depressant medications
  • 00:18:34
    over the last several decades okay
  • 00:18:37
    terrific and so when we look at
  • 00:18:40
    depression in this country or or uh
  • 00:18:43
    around the world um what are the rates
  • 00:18:46
    of depression like are things going up
  • 00:18:48
    or down yeah so it's unfortunate that uh
  • 00:18:52
    I mean the encouraging thing over the
  • 00:18:53
    last few decades is that compared to say
  • 00:18:56
    the 1980s or the 1990s when I started
  • 00:18:58
    doing brain Imaging research there's a
  • 00:19:00
    lot less stigma of Remnant Al Health
  • 00:19:02
    than there was and that that's certainly
  • 00:19:03
    very encouraging there are a lot more
  • 00:19:05
    people seeking treatment than before and
  • 00:19:07
    people are seeking treatments with
  • 00:19:08
    medications and uh and with
  • 00:19:10
    Psychotherapy more more than ever the
  • 00:19:13
    problem is that this hasn't changed the
  • 00:19:14
    numbers at all so despite the fact that
  • 00:19:17
    there's less stigma despite the fact
  • 00:19:19
    that people are coming forward and
  • 00:19:20
    taking anti-depressants and that in fact
  • 00:19:22
    antidepressant are being used in sex
  • 00:19:23
    quantities that they can be detected
  • 00:19:25
    with spectroscopes um in the in the
  • 00:19:28
    Water Supplies of of cities and so on so
  • 00:19:30
    they'll actually be able to go and they
  • 00:19:32
    can detect Trace Amounts of all these
  • 00:19:34
    medications um in City Water Supplies
  • 00:19:37
    despite all of this the prevalence of
  • 00:19:39
    depression and of suicidal acts and
  • 00:19:42
    suicidality has not gone down at all and
  • 00:19:44
    in certain populations like younger
  • 00:19:47
    folks uh under age 20 and in the early
  • 00:19:49
    20s the numbers for depression anxiety
  • 00:19:51
    and suicidality are going up rather than
  • 00:19:53
    down so we definitely need uh to put the
  • 00:19:56
    search on to understand how how
  • 00:19:58
    depression works in the brain and really
  • 00:19:59
    develop a new generation of treatments
  • 00:20:02
    uh because what we're having right now
  • 00:20:03
    is not moving the needle why do you
  • 00:20:05
    suppose the numbers are going
  • 00:20:07
    up there are a lot of different uh
  • 00:20:09
    possibilities for why that is there I I
  • 00:20:11
    think we could probably have a whole
  • 00:20:13
    other podcast on what that is in a
  • 00:20:15
    nutshell there are more there seem to be
  • 00:20:17
    more situations where people feel like
  • 00:20:19
    the fight is unwinable uh when I see
  • 00:20:21
    that it numbers for depression and
  • 00:20:22
    suicidality going up it's sort of an
  • 00:20:24
    index of number of people who feel like
  • 00:20:26
    they are losing at life and uh that
  • 00:20:28
    there's no way out for them so it is a
  • 00:20:30
    bit of a barometer of of social health
  • 00:20:32
    in that way uh some people have also
  • 00:20:34
    attributed to increased stressors around
  • 00:20:37
    social media use and so on and some
  • 00:20:38
    people have even attributed to things
  • 00:20:40
    like changes in the composition of the
  • 00:20:42
    bacteria that live within our guts some
  • 00:20:44
    of which appear to have a protective
  • 00:20:46
    effect against depression so um there
  • 00:20:48
    are a lot of theories out there but I
  • 00:20:49
    wouldn't say anyone has solved the
  • 00:20:51
    mystery as of what it is there are uh
  • 00:20:52
    lots of people prosing everything from
  • 00:20:54
    social factors to uh psychological
  • 00:20:57
    factors to biolog olcal factors like uh
  • 00:20:59
    literally right down to the bacteria in
  • 00:21:00
    a person's gut ah so so what do you
  • 00:21:03
    think about the pharmaceutical
  • 00:21:04
    treatments for depression are they are
  • 00:21:07
    they useful are they
  • 00:21:09
    neutral well I would say that I can give
  • 00:21:11
    you what the numbers say so if a person
  • 00:21:13
    comes into their family doctor with an
  • 00:21:15
    episode of depression and they try an
  • 00:21:17
    anti-depressant uh there was a famous
  • 00:21:19
    study about 15 years ago called stard D
  • 00:21:22
    LED out of the University of Texas
  • 00:21:23
    Southwestern and they found that uh
  • 00:21:26
    about 2third of people people could get
  • 00:21:29
    to remission from depression after
  • 00:21:32
    trying one medication or two medications
  • 00:21:34
    or three medications or four medications
  • 00:21:36
    one after the other but the numbers
  • 00:21:38
    really Dro precipitously so about
  • 00:21:39
    one-third of people would get better at
  • 00:21:41
    trying the first medication they ever
  • 00:21:42
    tried only about onethird about a
  • 00:21:44
    quarter of people would get better on
  • 00:21:46
    the second medication they tried but by
  • 00:21:48
    the time you've tried two medications
  • 00:21:50
    without success the third and the fourth
  • 00:21:51
    one are down to you know around 8 to 12%
  • 00:21:55
    success rates not particularly high at
  • 00:21:57
    all so so we're unfortunately a
  • 00:21:59
    situation where the medications tend to
  • 00:22:01
    work by fairly similar mechanisms in
  • 00:22:03
    terms of boosting serotonin levels or
  • 00:22:04
    boosting norrine levels or or dopamine
  • 00:22:07
    levels and so on and so yes you try to
  • 00:22:10
    influence the person's depression by
  • 00:22:11
    influencing these neurotransmitters in
  • 00:22:13
    the brain but at least onethird of
  • 00:22:15
    people don't get any benefit from them
  • 00:22:17
    and unfortunately a lot of people
  • 00:22:18
    relapse and uh a very large percentage
  • 00:22:21
    of people about 25% of people stop
  • 00:22:23
    taking medications early because of side
  • 00:22:25
    effects so I don't want to run down
  • 00:22:27
    medic
  • 00:22:28
    because the upside is that you know it's
  • 00:22:31
    in some ways it's quite remarkable that
  • 00:22:32
    you can take somebody who's despairing
  • 00:22:34
    about where their life is going and all
  • 00:22:36
    you ask them to do is take 10 seconds
  • 00:22:38
    out of their day to take a serotonin
  • 00:22:40
    boosting medication or a norepinephrine
  • 00:22:42
    boosting medication just at bedtime with
  • 00:22:43
    their toothbrush and it is quite
  • 00:22:45
    remarkable that just by doing that one
  • 00:22:47
    little thing a certain percentage of
  • 00:22:48
    people will emerge from depress spare
  • 00:22:50
    and suicidality and be able to face the
  • 00:22:52
    world again so that's the upside of it
  • 00:22:54
    the downside is that there's also a very
  • 00:22:56
    large number of people who don't get
  • 00:22:57
    better on the medications and a very
  • 00:22:59
    large number of people who can't
  • 00:23:00
    tolerate the medications so tell me
  • 00:23:01
    about recent breakthroughs in our
  • 00:23:05
    understanding so we're in what I would
  • 00:23:08
    argue is actually one of the most
  • 00:23:09
    exciting periods of Discovery within all
  • 00:23:12
    of uh within all of medicine so
  • 00:23:14
    psychiatry in particular a field called
  • 00:23:16
    Interventional Psychiatry is now looking
  • 00:23:19
    at all the traditional disorders like
  • 00:23:22
    depression anxiety and so on in terms of
  • 00:23:24
    brain circuitry and in terms of brain
  • 00:23:26
    function uh and thanks to 25 years of
  • 00:23:29
    brain Imaging research we're actually
  • 00:23:30
    starting to get really lovely maps of
  • 00:23:33
    where stuff happens in the brain and
  • 00:23:35
    what brain circuits are involved in
  • 00:23:36
    depression anxiety OCD post-traumatic
  • 00:23:40
    stress disorder Eating Disorders pretty
  • 00:23:42
    much most of the of the major categories
  • 00:23:46
    of mental health disorders we are
  • 00:23:48
    starting to get really great maps of
  • 00:23:50
    what areas of the brain are affected in
  • 00:23:51
    them the thing that's making that
  • 00:23:53
    knowledge useful is that we're also
  • 00:23:55
    starting to really take advantage now of
  • 00:23:57
    a new generation of brain stimulation
  • 00:24:00
    treatments um inspired by the kinds of
  • 00:24:03
    cases that I told you about at the
  • 00:24:05
    beginning of our conversation uh which
  • 00:24:07
    can go into those circuits which may be
  • 00:24:09
    overactive or underactive and can
  • 00:24:12
    actually stimulate them and reset them
  • 00:24:14
    back to their normal pattern of
  • 00:24:17
    activity so these new generation of of
  • 00:24:19
    treatments are brain stimulation
  • 00:24:21
    treatments and what's important about
  • 00:24:22
    them is they're anatomically precise
  • 00:24:24
    some of them as I mentioned before
  • 00:24:26
    involve implantable devices like deep
  • 00:24:29
    brain stimulators and for the last 20
  • 00:24:32
    years people have been pioneering and
  • 00:24:33
    starting to come up with ways that they
  • 00:24:35
    can actually implant little Pacemakers
  • 00:24:37
    in the brains of people who have very
  • 00:24:39
    serious forms of depression where
  • 00:24:40
    nothing has worked and uh these deep
  • 00:24:43
    brain stimulators have caused quite
  • 00:24:44
    remarkable ability of people to turn
  • 00:24:46
    around and immerse from their depression
  • 00:24:48
    but of course we also have the issue
  • 00:24:49
    that not everybody wants to have a
  • 00:24:51
    pacemaker implant in their brain and so
  • 00:24:52
    it would be really really useful if they
  • 00:24:55
    could undergo a different form of
  • 00:24:57
    treatment that was noninvasive and so
  • 00:24:59
    the other kind of treatment that's
  • 00:25:01
    really taking off right now uh involves
  • 00:25:03
    a treatment approved by the FDA in 2008
  • 00:25:05
    called transcranial magnetic stimulation
  • 00:25:09
    transcranial magnetic stimulation
  • 00:25:10
    involves using a powerful Focus magnetic
  • 00:25:14
    pulse generator uh placed it looks like
  • 00:25:17
    a little pingpong paddle it's sort of
  • 00:25:18
    placed against the scalp uh you place it
  • 00:25:20
    over the target circuit that you want to
  • 00:25:22
    stimulate and with the magnetic pulses
  • 00:25:24
    you're able to actually stimulate and
  • 00:25:26
    activate targets circuits in the brain
  • 00:25:28
    without needing any surgery they're
  • 00:25:30
    quite powerful so even though they're
  • 00:25:31
    magnetic pulses these are not you know
  • 00:25:33
    fridge magnets like if you were to place
  • 00:25:35
    this uh this paddle over the precise
  • 00:25:38
    spot on your brain that moves your thumb
  • 00:25:40
    and I were to press the button and cause
  • 00:25:43
    a couple of little pulses you would
  • 00:25:44
    actually see your your thumb or your
  • 00:25:46
    hand move with every single pulse uh so
  • 00:25:49
    these are ways of actually stimulating
  • 00:25:50
    Target regions in the brain and by
  • 00:25:52
    stimulating them over and over again
  • 00:25:54
    hundreds of times a day you can
  • 00:25:56
    gradually strengthen the con Connections
  • 00:25:58
    in areas of the brain that require
  • 00:26:00
    strengthening or you can reduce the
  • 00:26:02
    strength of the connections in areas
  • 00:26:04
    that I guess are overc connected and
  • 00:26:06
    with these two approaches you can try to
  • 00:26:08
    return the brain or reset the brain back
  • 00:26:11
    to its normal pattern of activity that
  • 00:26:13
    occurs when they are not in this mode of
  • 00:26:16
    Despair and folding and how did uh how
  • 00:26:19
    was this figured out about which brain
  • 00:26:21
    areas to
  • 00:26:23
    zap so the uh the work on this began all
  • 00:26:26
    the way back and then I 1980s when they
  • 00:26:28
    started using pet scanners uh which
  • 00:26:30
    inject a radioactive die to look at the
  • 00:26:32
    metabolism of the brain and they were
  • 00:26:35
    able to compare the brain activity of
  • 00:26:37
    people with depression and people who
  • 00:26:39
    were not in depression um and so the
  • 00:26:41
    first maps of these came out in the late
  • 00:26:43
    1980s and early 1990s and they
  • 00:26:45
    pinpointed a set of areas in the frontal
  • 00:26:48
    loes and also elsewhere in the brain
  • 00:26:50
    that seem to be consistently underactive
  • 00:26:52
    in people with depression they also
  • 00:26:54
    pinpointed areas of the brain that were
  • 00:26:57
    consistently overactive in people with
  • 00:26:59
    depression those ones appear to be
  • 00:27:01
    deeper in and this led to a new
  • 00:27:03
    generation of treatments where people us
  • 00:27:05
    the transcranial magnetic simulation
  • 00:27:07
    devices to Target the frontal o areas
  • 00:27:09
    near the surface because the magnetic
  • 00:27:11
    pulses could read them they also went to
  • 00:27:13
    the surgeons and began using the deep
  • 00:27:15
    brain simulator electrodes which despite
  • 00:27:18
    their name as stimulators can actually
  • 00:27:20
    be used to inhibit and disrupt areas of
  • 00:27:22
    the brain that are overactive and so
  • 00:27:24
    they were able to implant these in the
  • 00:27:26
    areas of the brain that were deeper and
  • 00:27:28
    overactive in depression and use them to
  • 00:27:31
    reset their activity so I recently did
  • 00:27:33
    an episode on uh how brains simulate the
  • 00:27:37
    future this is one of the main jobs of
  • 00:27:39
    brains is to simulate and evaluate
  • 00:27:42
    possible Futures what's your
  • 00:27:43
    interpretation of what happens when
  • 00:27:45
    somebody is depressed in terms of the
  • 00:27:47
    Futures that they are simulating so
  • 00:27:51
    that's that's a fascinating question um
  • 00:27:53
    and I I think there actually are some
  • 00:27:55
    really lovely brain Imaging studies that
  • 00:27:56
    were done on this
  • 00:27:58
    about 10 years ago led by Adam gazale
  • 00:28:01
    and some other folks over at UCSF what
  • 00:28:04
    they noticed was that uh perhaps in your
  • 00:28:06
    discussion you talked about a a set a
  • 00:28:08
    network of areas in the brain called the
  • 00:28:09
    default mode network uh the default mode
  • 00:28:12
    Network seems is name that because it
  • 00:28:14
    seems to be one of the most uh you know
  • 00:28:16
    it's the area of the brain that is on by
  • 00:28:17
    default when we're not doing anything
  • 00:28:18
    else so if you or I are sitting in a
  • 00:28:20
    room quietly and there's nothing going
  • 00:28:22
    on our default mode Network turns on and
  • 00:28:24
    as we've all experienced that involve
  • 00:28:26
    what happens in our mind as our brains
  • 00:28:28
    start thinking about the past and
  • 00:28:29
    thinking about the future and making
  • 00:28:30
    plans and thinking about what may take
  • 00:28:32
    place there are two Pathways by which we
  • 00:28:34
    do that there's a so-called reward
  • 00:28:36
    pathway where our brain thinks about
  • 00:28:38
    opportunities and things we might start
  • 00:28:40
    to want or desire to get us up out of
  • 00:28:42
    our seats and get going but there's also
  • 00:28:44
    a second pathway uh called the
  • 00:28:46
    non-reward pathway whose job it is
  • 00:28:48
    entirely to think about non-rewarding
  • 00:28:50
    outcomes things that could go wrong
  • 00:28:52
    fires I have to put out problems in my
  • 00:28:54
    life things that I should be motivated
  • 00:28:55
    to go and sort out uh and we we need
  • 00:28:57
    both of those to work in Balance so we
  • 00:28:59
    both need the ability to come up with
  • 00:29:01
    ideas for opportunities and things that
  • 00:29:03
    we desire to do but we also need to be
  • 00:29:06
    guided by all the problems in life all
  • 00:29:08
    the things that we really need to be
  • 00:29:10
    motivated to take care of and with a
  • 00:29:13
    balance between those two we can both
  • 00:29:14
    pursue opportunities in the future and
  • 00:29:16
    we can also avoid threats and problems
  • 00:29:18
    and uh and resolve them the problem in
  • 00:29:21
    depression occurs when this so-called
  • 00:29:23
    non-reward pathway whose whole job is to
  • 00:29:25
    think about all negative consequences
  • 00:29:27
    things that are going wrong things could
  • 00:29:28
    that could screw up um it can get
  • 00:29:30
    trapped in a sort of self-perpetuating
  • 00:29:32
    feedback loop so the circuit in the
  • 00:29:35
    brain is rrang as a bit of a loop um
  • 00:29:37
    from the frontal loes going down into
  • 00:29:39
    the the reward and motivational
  • 00:29:40
    structures of the brain and as uh if it
  • 00:29:44
    gets stuck in a loop what happens is the
  • 00:29:46
    person experiences just finding that
  • 00:29:48
    even though there may be 99 things that
  • 00:29:50
    are going well in the person's life
  • 00:29:52
    their brain will find the one thing
  • 00:29:54
    that's going wrong and it will get stuck
  • 00:29:56
    on it and it will just Loop on it over
  • 00:29:57
    and over and over again I think most of
  • 00:30:00
    us know somebody as family friends
  • 00:30:01
    colleagues maybe even ourselves who tend
  • 00:30:03
    to do that who are always really good at
  • 00:30:05
    spotting the one problem and getting
  • 00:30:06
    stuck on it uh but in depression it
  • 00:30:08
    becomes true to a pathological extent
  • 00:30:10
    where they get so stuck on it that even
  • 00:30:11
    with effort they cannot pull themselves
  • 00:30:13
    out of the negative circle of thoughts
  • 00:30:17
    which we call by the technical term
  • 00:30:19
    ruminations so in depression um this
  • 00:30:22
    non-reward pathway has gotten stuck in a
  • 00:30:24
    loop and what the person experiences is
  • 00:30:26
    an endless circle of ruminations and
  • 00:30:29
    self-criticism and thoughts about all
  • 00:30:31
    the possible Futures that will go wrong
  • 00:30:33
    and all the past things that have gone
  • 00:30:34
    wrong and it just becomes very difficult
  • 00:30:37
    to pull yourself out of this even when
  • 00:30:38
    you need to and so what is the
  • 00:30:40
    transcranial magnetic stimulation doing
  • 00:30:43
    when you are hitting a particular area
  • 00:30:45
    is it giving a second bite at the Apple
  • 00:30:49
    for that area to rewire is it simply
  • 00:30:52
    making the area more plastic so that it
  • 00:30:54
    has an opportunity to wire up um in a
  • 00:30:57
    more beneficial way the next time around
  • 00:31:00
    so I'll give you our best guess as to
  • 00:31:02
    what's happening right now as with many
  • 00:31:04
    things in psychiaty we discovered that
  • 00:31:06
    these things worked long before we
  • 00:31:07
    actually figured out why they worked um
  • 00:31:10
    but the the original areas of the brain
  • 00:31:12
    that we stimulated were were targeted
  • 00:31:15
    because they just seem to be underactive
  • 00:31:16
    in depression so the theory was look
  • 00:31:18
    they're underactive let's use this brain
  • 00:31:19
    stimulator let's stimulate them let's
  • 00:31:21
    turn them back on and then all will be
  • 00:31:22
    well later on we discovered that what
  • 00:31:25
    these areas really seem to be associated
  • 00:31:26
    with is courage and resilience in other
  • 00:31:29
    words people who happen just by chance
  • 00:31:32
    to have more gray matter or born with
  • 00:31:34
    more gray matter in these areas they're
  • 00:31:36
    more resilient to stress they have
  • 00:31:37
    better ability to cope these brain areas
  • 00:31:40
    in the frontal lobes are in are engaged
  • 00:31:42
    every time we do a thing called
  • 00:31:44
    cognitive control which is our ability
  • 00:31:45
    to self-regulate our thoughts and our
  • 00:31:47
    behaviors and emotions in fact for those
  • 00:31:49
    of you who've tried mindfulness
  • 00:31:51
    meditation if you've ever sat in a chair
  • 00:31:53
    and tried to not ruminate and tried to
  • 00:31:54
    focus on your breathing uh every time
  • 00:31:56
    you notice that your mind is wandering
  • 00:31:59
    and you shut down the ruminations and
  • 00:32:01
    come back to your breathing again you
  • 00:32:02
    turn on this network of areas it looks
  • 00:32:05
    like what we're doing with TMS is
  • 00:32:06
    actually not so much pushing happiness
  • 00:32:08
    into the brain or pulling anxiety out
  • 00:32:10
    but more generally strengthening the
  • 00:32:12
    very same network that is activated when
  • 00:32:15
    you do mindfulness meditation uh and so
  • 00:32:17
    when I talk to patients about what it's
  • 00:32:20
    like for them after the TMS has worked
  • 00:32:22
    they talk a lot about how something
  • 00:32:23
    stressful happened this week and
  • 00:32:25
    normally it would have ruined my whole
  • 00:32:26
    week but noticed that I just got over it
  • 00:32:28
    I kind of thought about it and realized
  • 00:32:30
    it wasn't as bad as and I was able to
  • 00:32:32
    kind of cope with it they describe it as
  • 00:32:34
    as having more coping capacity and so it
  • 00:32:36
    looks like the effects of TMS on
  • 00:32:38
    depression at least with the sander
  • 00:32:40
    areas might be somewhat indirect you're
  • 00:32:41
    not so much pushing happiness in or
  • 00:32:43
    taking anxiety out but you are
  • 00:32:45
    strengthening a sort of mental muscle
  • 00:32:47
    for cognitive control and as a result
  • 00:32:49
    people just generally get better at
  • 00:32:51
    self-regulating their thoughts and
  • 00:32:53
    behaviors and emotions and they can cope
  • 00:32:54
    with more stress so things don't feel
  • 00:32:56
    quite quite as defeating things don't
  • 00:32:58
    look quite as bad I I I've been sort of
  • 00:33:01
    playing with a different interpretation
  • 00:33:02
    slightly about it which is that you are
  • 00:33:06
    uh to phrase it colloquially you're sort
  • 00:33:08
    of loosening up a Network that has found
  • 00:33:12
    itself getting into a particular way um
  • 00:33:16
    a particular structure and what you're
  • 00:33:17
    doing is reintroducing plasticity to
  • 00:33:20
    that area so that you have a chance of
  • 00:33:23
    things running correctly through there
  • 00:33:25
    and with TMS is as we know sometimes the
  • 00:33:29
    first treatment doesn't work but the
  • 00:33:31
    second treatment does my view on that is
  • 00:33:34
    that it's you know possible that after
  • 00:33:36
    the first time the system Recon
  • 00:33:39
    converges into some
  • 00:33:42
    pathological wiring and then you know if
  • 00:33:44
    you do it again you're getting another
  • 00:33:46
    chance to have it find uh better
  • 00:33:49
    wiring yeah I'm really glad you brought
  • 00:33:52
    that up because I think that actually
  • 00:33:53
    lines up really well with a very recent
  • 00:33:56
    discovery that's still quite new um uh
  • 00:33:59
    about what is happening for people who
  • 00:34:01
    are trying um a second form of rtms that
  • 00:34:05
    kicks in when the first one doesn't work
  • 00:34:06
    so when I say rtms I'm it's repetitive
  • 00:34:09
    transcranial magnetic stimulation it's
  • 00:34:11
    effectively TMS treatment but you're
  • 00:34:13
    using these repetitive pulses so some
  • 00:34:15
    people will call it rtms and some people
  • 00:34:17
    will simply just abbreviate it to TMS
  • 00:34:19
    but we're talking about using this
  • 00:34:20
    non-invasive stimulation so when a
  • 00:34:22
    person goes through and does the
  • 00:34:23
    treatment using the standard parameters
  • 00:34:25
    that I talked about sometimes it works
  • 00:34:27
    and yet there's a percentage of people
  • 00:34:29
    where it doesn't work what we've noticed
  • 00:34:31
    that those people tend to have higher
  • 00:34:32
    scales on rumination negative
  • 00:34:34
    ruminations about life uh and a lovely
  • 00:34:37
    study came out by a group led by Andy
  • 00:34:39
    luer at UCLA where he was able to
  • 00:34:41
    identify that these people have higher
  • 00:34:43
    rumination scores um they then move the
  • 00:34:46
    coil to a different area so instead of
  • 00:34:48
    stimulating the first area that I talk
  • 00:34:50
    about they go to a different brain area
  • 00:34:52
    which actually sits within this
  • 00:34:54
    non-reward circuit that we were talking
  • 00:34:56
    about before and instead of trying to
  • 00:34:58
    stimulate and strengthen it uh sure
  • 00:34:59
    enough what they do is they try and
  • 00:35:01
    inhibit and disrupt the activity of this
  • 00:35:03
    area so they are trying to disrupt and
  • 00:35:06
    break up the feedback loop that they
  • 00:35:08
    call the non-reward attractor State uh
  • 00:35:11
    it's in fact a professor named Edmund
  • 00:35:12
    rolles that of Cambridge by the way just
  • 00:35:14
    described he came up with a theory of
  • 00:35:16
    depression which is very similar to what
  • 00:35:17
    you describe he called it the non-reward
  • 00:35:20
    attractor theory of depression that
  • 00:35:22
    non-reward circuit the more it runs and
  • 00:35:24
    the more it dwells on things the more it
  • 00:35:26
    strength the connections in and of
  • 00:35:28
    itself so it becomes self strengthening
  • 00:35:29
    self-perpetuating and just you're just
  • 00:35:31
    going to get stuck in this so-called
  • 00:35:33
    attractor State and not be able to get
  • 00:35:35
    out of it the solution with TMS would be
  • 00:35:37
    to put the coil over those areas and
  • 00:35:40
    apply some pulses of stimulation not to
  • 00:35:42
    strengthen the pathway that's not what
  • 00:35:43
    we want but to disrupt and weaken the
  • 00:35:45
    connections through uh neuroplasticity
  • 00:35:48
    to the point where the person can now
  • 00:35:49
    pull themselves out again that's your
  • 00:35:51
    interpretation of what trans cranial
  • 00:35:53
    magnetic stimulation does right yeah so
  • 00:35:56
    we're still fig figuring this out but
  • 00:35:57
    what we think is that for some people
  • 00:35:58
    when you strengthen the first circuit
  • 00:36:01
    and they regain their cognitive control
  • 00:36:03
    that circuit is is connected to the
  • 00:36:05
    non-reward Circuit so they can then use
  • 00:36:07
    their cognitive control to do this work
  • 00:36:08
    themselves of popping themselves out of
  • 00:36:10
    this attractor state for in other people
  • 00:36:12
    for whatever reason these two Pathways
  • 00:36:14
    aren't really very well connected so
  • 00:36:15
    they kind of operate independently so
  • 00:36:17
    you strengthen the first pathway they
  • 00:36:19
    get more coping capacity but the problem
  • 00:36:21
    is they're still stuck in these negative
  • 00:36:22
    ruminations then you bring them back
  • 00:36:24
    again you move the stimulator over to
  • 00:36:26
    this other pathway I actually had a
  • 00:36:28
    patient who described it saying this F
  • 00:36:30
    your first treatment didn't work but the
  • 00:36:32
    second one you gave me over this
  • 00:36:33
    non-reward pathway I he said I'm
  • 00:36:36
    definitely one of those people you
  • 00:36:37
    talked about who always finds the one
  • 00:36:39
    negative thing in the room and if I see
  • 00:36:41
    it it's like a neg he said it's like an
  • 00:36:43
    escalator I'm forced to get on the
  • 00:36:45
    escalator and ride it down down down all
  • 00:36:47
    the way to the bottom and then I'm just
  • 00:36:49
    stuck there I could be stuck there for
  • 00:36:50
    days or weeks and after I finished the
  • 00:36:53
    course of treatment something really
  • 00:36:54
    horrible happened and I thought oh boy
  • 00:36:56
    here we go go I'm going to be dragged
  • 00:36:57
    down the escalator and it just didn't
  • 00:36:59
    happen I noticed the way he said it he
  • 00:37:01
    says it's like I walked up to the top of
  • 00:37:03
    this escalator I saw where it was going
  • 00:37:05
    and I realized I didn't want to go down
  • 00:37:06
    there and so my brain just kept going
  • 00:37:09
    and I think what's interesting on the
  • 00:37:11
    brain Imaging study is of course if you
  • 00:37:13
    scan people before and after what you
  • 00:37:14
    find is exactly what you described that
  • 00:37:16
    the connections between within this
  • 00:37:19
    circuit are actually getting disrupted
  • 00:37:20
    and weaken so uh the circuit's still
  • 00:37:22
    there and functioning but it's not
  • 00:37:23
    getting stuck in this attractor state or
  • 00:37:26
    this Loop so I think it actually lines
  • 00:37:28
    up really well with the account you just
  • 00:37:29
    described in the one case plasticity
  • 00:37:31
    being used to strengthen the person's
  • 00:37:33
    ability to control their thoughts but if
  • 00:37:35
    that doesn't work in the other case you
  • 00:37:37
    can then go directly to the area that's
  • 00:37:39
    stuck in a loop in the first place and
  • 00:37:41
    use another form of plasticity to weaken
  • 00:37:43
    those connections and loosen them so the
  • 00:37:45
    person can come out of it again yeah and
  • 00:37:47
    this is very cool because originally
  • 00:37:50
    with depression I mean I think it's
  • 00:37:51
    always been this way historically that
  • 00:37:53
    people let's say loved ones who are with
  • 00:37:55
    somebody who's depressed feel like hey
  • 00:37:57
    we should just be able to talk The
  • 00:37:59
    person out of this just say hey look at
  • 00:38:00
    the bright side and so on that that
  • 00:38:02
    doesn't work and so this idea of being
  • 00:38:06
    able to help
  • 00:38:08
    somebody by let's say loosening up
  • 00:38:11
    circuits in the brain doing other thing
  • 00:38:13
    you know getting someone out of an
  • 00:38:14
    attractor State uh
  • 00:38:17
    non-invasively is is so promising uh
  • 00:38:20
    what do you predict is going to be the
  • 00:38:22
    field in in 40 years from now when
  • 00:38:24
    you're when you're elderly oh wow that's
  • 00:38:28
    that's really interesting I I I'll get
  • 00:38:29
    to that in a moment I but I I want to
  • 00:38:31
    just come back and highlight that I
  • 00:38:33
    think you really hit the nail on the
  • 00:38:34
    head with this that uh every one of us
  • 00:38:37
    has tried to talk someone who's
  • 00:38:38
    despairing out of their despair we've
  • 00:38:40
    all tried to do it and we've all been
  • 00:38:42
    sort of SED and frustrated going why are
  • 00:38:44
    you fighting us on this like we I keep
  • 00:38:46
    trying to tell you all the things that
  • 00:38:47
    are good in life and reminds you of them
  • 00:38:49
    and it's almost like you want your brain
  • 00:38:50
    wants to just go to the one negative
  • 00:38:52
    thing and stuck there you've had that
  • 00:38:54
    experience in talking to somebody I'm
  • 00:38:55
    sure we all have um and it comes back to
  • 00:38:58
    exactly that lesson that depression is a
  • 00:39:01
    kind of motivated State it's the the
  • 00:39:02
    brain is turning this on because it
  • 00:39:04
    thinks that it needs to be in this
  • 00:39:06
    survival mechanism of just folding and
  • 00:39:08
    giving up it thinks that that's its best
  • 00:39:09
    chance of survival and so it's a highly
  • 00:39:11
    motivated State and you will not be able
  • 00:39:13
    to talk somebody out of it because their
  • 00:39:15
    their motivational circuitry literally
  • 00:39:17
    has been hijacked by the depression uh
  • 00:39:20
    and so just talking people out of it
  • 00:39:21
    doesn't work terribly well but as you
  • 00:39:23
    say now that we know where this
  • 00:39:25
    motivational lives now that we know
  • 00:39:27
    where this non-reward circuit lives we
  • 00:39:30
    can do all kinds of interventions and
  • 00:39:32
    you asked what's it going to look like
  • 00:39:34
    in 40 years I don't think there's going
  • 00:39:35
    to be any one treatment that is just
  • 00:39:39
    universally what people use uh I'll give
  • 00:39:41
    you an example of that so recently A
  • 00:39:43
    couple of years ago a team at UC San
  • 00:39:45
    Francisco led by uh Katherine scango and
  • 00:39:48
    colleagues they were able to go to this
  • 00:39:51
    non-reward circuit in the brain that I
  • 00:39:52
    talked about uh and they took people who
  • 00:39:55
    had very severe depression and they did
  • 00:39:57
    something that I think is very kind of
  • 00:39:58
    futuristic first of all they brought
  • 00:40:00
    them into a special monitoring ward in
  • 00:40:03
    the hospital and they implanted little
  • 00:40:05
    electrodes in their brain and let them
  • 00:40:06
    stay in the hospital for several days or
  • 00:40:08
    weeks normally that's what you'll do in
  • 00:40:10
    epilepsy patients if you were trying to
  • 00:40:12
    find the source of the epilepsy within
  • 00:40:14
    the brain you'll put electrodes all over
  • 00:40:15
    the brain and you'll let them sit and
  • 00:40:16
    you wait for them to have seizures and
  • 00:40:18
    then you go back and reconstruct where
  • 00:40:20
    they came from so you can perform a
  • 00:40:21
    surgery and this case they said well you
  • 00:40:24
    know the folks with depression these
  • 00:40:25
    folks are really they can't function
  • 00:40:27
    they're suicidal you know they really
  • 00:40:29
    need something just as drastic as this
  • 00:40:30
    so they brought them in they implanted
  • 00:40:32
    the electrodes but instead of waiting
  • 00:40:33
    for seizures they just let them have
  • 00:40:35
    negative thoughts and using a little app
  • 00:40:37
    on their tablet they could constantly
  • 00:40:39
    rate what their brain was thinking about
  • 00:40:40
    and so you could see what kind of brain
  • 00:40:43
    activity was going on when they were
  • 00:40:44
    having positive thoughts or negative
  • 00:40:46
    thoughts um and by doing that and using
  • 00:40:48
    a machine learning algorithm they were
  • 00:40:50
    able to detect the electrodes that
  • 00:40:52
    showed particular pattern of abnormal
  • 00:40:55
    activity that was present when the brain
  • 00:40:57
    got sucked into those negative
  • 00:40:58
    ruminations when they did that they were
  • 00:41:00
    then able to implant a deep brain
  • 00:41:02
    stimulator in that uh and it was a
  • 00:41:04
    closed loop system so it was attached to
  • 00:41:06
    a tiny little computer that would uh
  • 00:41:08
    that would detect when the brain had
  • 00:41:10
    gone into this abnormal rhythm of
  • 00:41:12
    negative thoughts and it would just
  • 00:41:13
    disrupt the activity with about five or
  • 00:41:15
    six seconds of stimulation so it just
  • 00:41:17
    flip just to like when you tap on a
  • 00:41:19
    microphone to break a feedback loop it
  • 00:41:20
    was literally just tapping on that
  • 00:41:22
    microphone and saying hey stop it um
  • 00:41:24
    we've used this approach in the heart
  • 00:41:25
    for a long time so people have heart
  • 00:41:27
    rhythm problems can wear things called
  • 00:41:29
    implantable have a surgery to have an
  • 00:41:31
    implantable cardiac defibrillator so
  • 00:41:34
    something like the defibrillator paddles
  • 00:41:35
    that you might see in the airport but
  • 00:41:37
    this is actually implanted inside so if
  • 00:41:38
    their heart ever gets stuck in an
  • 00:41:40
    abnormal Rhythm that might be fatal the
  • 00:41:42
    device will automatically detect that
  • 00:41:44
    the heart's in that Rhythm and just give
  • 00:41:46
    a few blips to reset it so interestingly
  • 00:41:49
    they were doing the same thing in the
  • 00:41:50
    brain these folks had effectively
  • 00:41:52
    created an implantable brain
  • 00:41:53
    defibrillator and so it was detecting
  • 00:41:55
    when this abnormal pattern comes along
  • 00:41:57
    they blip it for a few seconds um and
  • 00:42:00
    there's a lovely article in the New York
  • 00:42:01
    Times a couple of years ago where they
  • 00:42:02
    interviewed the patient describe what it
  • 00:42:04
    was like and they talked about it as
  • 00:42:06
    being a sort of you're about to get
  • 00:42:08
    sucked down into these negative thoughts
  • 00:42:09
    and she said suddenly the rational side
  • 00:42:11
    of you comes on and those negative
  • 00:42:13
    emotions can be separated from your real
  • 00:42:16
    situation what was encouraging is that
  • 00:42:18
    this seems to this process of implanting
  • 00:42:20
    these stimulators seems to work even in
  • 00:42:22
    people who have had depression for
  • 00:42:24
    decades and have tried every other
  • 00:42:25
    treatment avail multiple medications
  • 00:42:27
    therapies TMS even electrc convulsive
  • 00:42:29
    therapy all kinds of things so people
  • 00:42:32
    have really gotten nowhere with the
  • 00:42:33
    other treatments uh using this targeted
  • 00:42:36
    intelligent approach I think that really
  • 00:42:38
    is sort of the Prototype of what the
  • 00:42:39
    future looks like yeah I think one of
  • 00:42:41
    the most amazing things about this U
  • 00:42:44
    many many listeners will already sort of
  • 00:42:45
    be aware of this research but generally
  • 00:42:49
    we think of ourselves and our
  • 00:42:51
    personalities and our thoughts and our
  • 00:42:53
    emotions as something different from
  • 00:42:56
    let's say our heart and how is our heart
  • 00:42:58
    functioning and you can defibrillate the
  • 00:42:59
    heart but the brain it feels like well
  • 00:43:02
    that's me that's just who I am and so on
  • 00:43:05
    and it's uh sort of an amazing
  • 00:43:07
    Revelation that that many people have
  • 00:43:09
    when they start seeing this sort of data
  • 00:43:11
    to understand that we are physical
  • 00:43:13
    creatures and when you um do things to
  • 00:43:17
    change the physical structure that
  • 00:43:18
    changes who you are in that moment I I
  • 00:43:21
    think that's spot on and that comes back
  • 00:43:23
    to the story we told at the beginning
  • 00:43:25
    why it was so interesting for me as a as
  • 00:43:27
    a young researcher um that you know at
  • 00:43:30
    that time many years ago we really there
  • 00:43:32
    were the default idea was this thing
  • 00:43:34
    called the serotonin hypothesis of
  • 00:43:36
    depression where you know serotonin had
  • 00:43:38
    something to do with your mood and if
  • 00:43:39
    your mood was low it was maybe because
  • 00:43:41
    your serotonin was low you you know
  • 00:43:42
    didn't have enough serotonin in your
  • 00:43:44
    soup so we should get out a serotonin
  • 00:43:46
    Shaker and we shake some put some more
  • 00:43:47
    serotonin into your soup and that will
  • 00:43:49
    somehow just you know make your mood get
  • 00:43:50
    better but uh it turns out of course
  • 00:43:53
    it's not as simple as that the serotonin
  • 00:43:55
    is not mood serotonin in you know in
  • 00:43:57
    your in your GI tract will will cause
  • 00:44:00
    your you know to have uh to have gi
  • 00:44:02
    motions uh in the brain stem it can
  • 00:44:04
    regulate nausea and the visual cortex it
  • 00:44:06
    can do visual things and so there's no
  • 00:44:08
    such thing as a really where just mood
  • 00:44:10
    is just boiled down to not having enough
  • 00:44:12
    of a molecule in place but when we
  • 00:44:15
    looked at those cases as you said were
  • 00:44:16
    people who had been depressed for so
  • 00:44:18
    long that they thought it was just part
  • 00:44:20
    of who they were uh they then have this
  • 00:44:22
    experience where you literally just take
  • 00:44:24
    a circuit in the brain and blip it and
  • 00:44:27
    reset it and the person immediately in
  • 00:44:29
    their thoughts is no longer getting
  • 00:44:31
    stuck in the negative thoughts and can
  • 00:44:33
    look past the one thing that's going
  • 00:44:35
    wrong to the other 9 things that are
  • 00:44:37
    going right through that clear sort of
  • 00:44:39
    logical way uh and you're right people
  • 00:44:40
    do really find it as a res as a
  • 00:44:42
    revelation and people who improve on
  • 00:44:44
    these they often find that because
  • 00:44:46
    they've been depressed for 20 years you
  • 00:44:47
    know they uh they don't it can be
  • 00:44:50
    actually quite a lot of work to sit down
  • 00:44:51
    with a person and figure out how to
  • 00:44:53
    reconstruct their life uh based on the
  • 00:44:55
    premise that they actually get up every
  • 00:44:56
    day and feel good and ready to do things
  • 00:44:58
    they have spent 20 years building a life
  • 00:45:00
    around disability so it's not something
  • 00:45:03
    where so there often can be quite a lot
  • 00:45:04
    of work done over months or years to try
  • 00:45:06
    and figure out how the person will adapt
  • 00:45:08
    to a life that has hope in it again yeah
  • 00:45:12
    so so you once told me how you see the
  • 00:45:14
    uh the battle against depression in the
  • 00:45:16
    21st century from a historical point of
  • 00:45:20
    view yeah so I mean I let's come back to
  • 00:45:23
    those numbers we talked about earlier on
  • 00:45:24
    where we said that there's a the
  • 00:45:26
    prevalence of depression over the
  • 00:45:28
    lifetime is maybe 10% and the prevalence
  • 00:45:30
    at any given time is about 5% now there
  • 00:45:33
    are lots of diseases uh in the history
  • 00:45:35
    of medicine where the prevalence uh has
  • 00:45:37
    come down a lot so people used there
  • 00:45:39
    used to be a lot of people with
  • 00:45:40
    tuberculosis that's come down a lot and
  • 00:45:42
    we're now making progress against
  • 00:45:43
    malaria we're making progress against
  • 00:45:45
    various forms of hepatitis we're making
  • 00:45:48
    progress against uh stomach ulcers that
  • 00:45:50
    used to sometimes be fatal if they
  • 00:45:51
    progress and for each of these things we
  • 00:45:53
    now have effective treatments and the
  • 00:45:55
    prevalence is coming down even for HIV
  • 00:45:57
    uh something that was once untreatable
  • 00:45:59
    and uncontrollable is now turned into
  • 00:46:01
    something that is controllable and that
  • 00:46:02
    over time we may be able to get the
  • 00:46:04
    prevalences down uh so the dream for us
  • 00:46:06
    I think for the 21st century would be
  • 00:46:08
    that we would like you know at the end
  • 00:46:10
    of our careers 40 years from now as you
  • 00:46:12
    said we'd like to be able to look back
  • 00:46:14
    at the prevalence of depression and
  • 00:46:16
    anxiety and other mental health
  • 00:46:18
    disorders and say look at that we used
  • 00:46:20
    to be at 5 or 10% and look how much
  • 00:46:22
    numbers have come down since then
  • 00:46:25
    millions of people who were had no
  • 00:46:27
    pathway forward uh now see depression as
  • 00:46:30
    something that is treatable um and
  • 00:46:32
    employers no longer look at depression
  • 00:46:34
    as something that would disqualify you
  • 00:46:36
    from being hired for a job oh you have
  • 00:46:38
    depression that's okay not the end of
  • 00:46:39
    the world just go in and get the course
  • 00:46:41
    of treatment and we'll see you we'll see
  • 00:46:42
    you back in a week or two so you know
  • 00:46:45
    this will help to erode the stigma and I
  • 00:46:46
    think we'll really get to see the
  • 00:46:48
    numbers coming down on this are we going
  • 00:46:50
    to get those millions of people better
  • 00:46:51
    with deep brain simulators alone no of
  • 00:46:53
    course not um we're not going to be
  • 00:46:55
    implanting Millions millions and
  • 00:46:56
    millions of deep brain simulators and
  • 00:46:57
    everybody not everybody wants them and
  • 00:46:59
    just there aren't off servic to do that
  • 00:47:01
    um but I think we do have a real
  • 00:47:03
    opportunity using the non-invasive forms
  • 00:47:05
    of brain stimulation like TMS which are
  • 00:47:08
    getting you know very very good as well
  • 00:47:10
    so your colleague over at uh over at
  • 00:47:13
    Stanford one of my good friends Nolan
  • 00:47:15
    Williams uh was instrumental in
  • 00:47:17
    developing a radical new form of TMS
  • 00:47:19
    treatment uh that could take a person
  • 00:47:22
    from severe depression on Monday all the
  • 00:47:24
    way down to being in remission in
  • 00:47:25
    literally 5 days uh the secret was to do
  • 00:47:29
    two things the first was not to do a
  • 00:47:30
    treatment once a day traditionally but
  • 00:47:32
    to do up to 10 treatments a day so that
  • 00:47:35
    a person can have 30 or 40 or 50
  • 00:47:36
    treatments in a week and that's
  • 00:47:38
    definitely enough TMS sessions to get
  • 00:47:39
    them better the second part of their
  • 00:47:41
    trick was actually perform some brain
  • 00:47:42
    Imaging in the person so you could see
  • 00:47:44
    what Pathways to be targeting and then F
  • 00:47:46
    tune and personalize where the coil is
  • 00:47:48
    through some combination of those two
  • 00:47:51
    things they seem to be hitting very high
  • 00:47:52
    success rates that are you know north of
  • 00:47:54
    50% so we have a tool now with TMS that
  • 00:47:58
    if you know someone who has struggled
  • 00:48:00
    with depression or anxiety and has not
  • 00:48:02
    done well on therapy or medications
  • 00:48:04
    that's a lot of people uh they can go
  • 00:48:06
    anywhere in the United States right now
  • 00:48:08
    to a TMS clinic and they can undergo a
  • 00:48:10
    course of transcranial magnetic
  • 00:48:12
    simulation and with the most recent FDA
  • 00:48:15
    approved protocols you we believe that
  • 00:48:17
    we can get more than 50% of people to
  • 00:48:19
    remission even if nothing else has
  • 00:48:20
    worked so we do think we have a tool
  • 00:48:23
    that is now capable of treating most
  • 00:48:25
    people with depression and getting at
  • 00:48:27
    least half of them out of depression
  • 00:48:29
    maybe more the trick is going to be to
  • 00:48:31
    scale that so just scaling up so that
  • 00:48:33
    everyone in the country will have access
  • 00:48:35
    to this treatment once we're there we I
  • 00:48:37
    think we will absolutely see
  • 00:48:39
    improvements in the prevalence in our
  • 00:48:41
    lifetimes it's great hey just dig into
  • 00:48:44
    one more thing because you talked I've
  • 00:48:46
    heard you talk before about tuberculosis
  • 00:48:48
    and the uh the the parallel
  • 00:48:51
    there yeah so that's an interesting
  • 00:48:53
    thing um it is possible I guess that our
  • 00:48:56
    battle against oppression in the 21st
  • 00:48:57
    century is really a little bit like the
  • 00:48:59
    battle against you know tuberculosis in
  • 00:49:01
    the 19th and TW and the 20th century um
  • 00:49:04
    one of the pioneers of modern medicine
  • 00:49:06
    the 19th century physician Sir William
  • 00:49:09
    Osler um he of course saw many patients
  • 00:49:12
    in his career with tuberculosis coming
  • 00:49:14
    from the poor areas of town the
  • 00:49:15
    overcrowded areas and so on uh the
  • 00:49:18
    places where living conditions were
  • 00:49:19
    terrible where sanitation was terrible
  • 00:49:21
    and as a result he described
  • 00:49:22
    tuberculosis as primarily quote a social
  • 00:49:26
    disease with a medical aspect in other
  • 00:49:29
    words yes we can treat it medically but
  • 00:49:31
    fundamentally tuberculosis isn't going
  • 00:49:33
    to go away until people have better
  • 00:49:34
    living conditions until you don't have
  • 00:49:36
    eight people living in one room and
  • 00:49:38
    until people aren't with bad food and
  • 00:49:39
    all the rest of it so in fact although
  • 00:49:42
    tuberculosis drugs were developed in the
  • 00:49:44
    20th century and saved millions of lives
  • 00:49:46
    when they invented the reality is that
  • 00:49:48
    the rates of tuberculosis were coming
  • 00:49:50
    down decades before any of these drugs
  • 00:49:53
    were ever rolled out to reach people and
  • 00:49:55
    the prevalence of tuberculosis improved
  • 00:49:57
    because people's lives improved you know
  • 00:49:59
    better food cleaner water less crowded
  • 00:50:02
    living conditions less dire poverty less
  • 00:50:05
    desperation and I think we're going to
  • 00:50:07
    see that a very similar thing is
  • 00:50:09
    happening here it's not that we won't be
  • 00:50:10
    able to use new technologies like brain
  • 00:50:12
    stimulation to pull people out of
  • 00:50:13
    Despair but it's also possible that a
  • 00:50:16
    key to getting people out of Despair
  • 00:50:17
    will be to understand depression also as
  • 00:50:19
    to some degree a social disease with a
  • 00:50:21
    medical aspect if we go back to the idea
  • 00:50:24
    that depression is the thing that
  • 00:50:26
    happens when the brain has decided it's
  • 00:50:27
    in a battle for survival that it's not
  • 00:50:29
    going to win then we look at the
  • 00:50:31
    prevalence of depression as a number of
  • 00:50:33
    people who look around at their lives
  • 00:50:34
    and included that they are in an
  • 00:50:36
    unwinable
  • 00:50:37
    situation and I believe in the same way
  • 00:50:40
    that we part of the pathway to getting
  • 00:50:42
    people out of depression and reducing
  • 00:50:44
    its prevalence will be improving the
  • 00:50:46
    conditions of people's lives their the
  • 00:50:48
    degree to which they feel secure the
  • 00:50:50
    degree to which they don't feel like
  • 00:50:51
    they're going to lose their housing or
  • 00:50:53
    to be under threat of violence the first
  • 00:50:55
    first places in the world to overcome
  • 00:50:57
    depression will be the ones that don't
  • 00:50:59
    just develop you know better
  • 00:51:01
    Technologies to reset the brain but also
  • 00:51:03
    develop stronger Societies in which we
  • 00:51:06
    just have fewer percentages of people
  • 00:51:08
    who are trapped in fights for survival
  • 00:51:09
    that they feel like and never seem to
  • 00:51:11
    win and I guess that's maybe there is a
  • 00:51:15
    concept which one of my uh colleagues
  • 00:51:17
    introduced me to from the history of
  • 00:51:19
    Judaism and it's it's a lovely phrase
  • 00:51:21
    that I just really carry around with me
  • 00:51:23
    all day it's a the phrase is
  • 00:51:26
    uh and it has been described to me as
  • 00:51:29
    the religious injunction to repair the
  • 00:51:31
    world yeah I can't I think you and I
  • 00:51:34
    have also discussed this in the past as
  • 00:51:35
    well yeah so yeah when we talk about
  • 00:51:39
    resetting the brain I think that falls
  • 00:51:40
    within the larger of battle to try and
  • 00:51:42
    improve the lot of humanity and reduce
  • 00:51:44
    them reduce despair everywhere and uh so
  • 00:51:47
    when I think about the pathway to tun
  • 00:51:49
    Alam and what neuros signs can
  • 00:51:52
    contribute to it and what uh you know
  • 00:51:54
    brain stimulation can can can contribute
  • 00:51:56
    to it I think it has an essential um
  • 00:51:59
    role in reducing the number of people
  • 00:52:01
    who face the world in Despair and that
  • 00:52:03
    will be an essential component of this m
  • 00:52:05
    arure injunction to repair the world
  • 00:52:07
    which I think we can all relate
  • 00:52:10
    [Music]
  • 00:52:12
    to I spend many of these episodes
  • 00:52:15
    talking about the extraordinary things
  • 00:52:17
    that the brain does well but it's
  • 00:52:20
    equally important to talk about what
  • 00:52:22
    happens when the brain gets off track
  • 00:52:25
    because some percentage of your friends
  • 00:52:27
    and loved ones are going to have to
  • 00:52:29
    battle depression at some point and it
  • 00:52:32
    might be a slightly higher percentage
  • 00:52:35
    than you think the brain is incredible
  • 00:52:38
    but fragile and what we see from
  • 00:52:41
    depression is that it's relatively easy
  • 00:52:44
    for it to slip out of its optimal
  • 00:52:46
    operating range happily Neuroscience
  • 00:52:50
    Labs all over the world are working to
  • 00:52:53
    understand this and researchers and
  • 00:52:56
    companies are generating new approaches
  • 00:52:59
    as with trans cranial magnetic
  • 00:53:01
    stimulation such that as we move forward
  • 00:53:05
    we will have increasingly better ways to
  • 00:53:08
    get things back on
  • 00:53:13
    track go to eagan.mn
  • 00:53:22
    with questions or discussion and I'll be
  • 00:53:25
    making monthly episodes in which I
  • 00:53:27
    address those and check out and
  • 00:53:29
    subscribe to Inner Cosmos on YouTube for
  • 00:53:32
    videos of each episode and to leave
  • 00:53:34
    comments until next time I'm David
  • 00:53:37
    Eagleman and this is inner
  • 00:53:51
    Cosmos
タグ
  • depressão
  • neurociência
  • tratamento
  • David Eagleman
  • estimulação cerebral
  • TMS
  • evolução da depressão