Putting the Mental Back into Mental Disorders

November 18, 2022

YCSC Grand Rounds November 15, 2022

Joseph LeDoux, PhD
Director, The Emotional Brain Institute, NYU
Professor of Neural Science and Psychology, NYU
Professor of Psychiatry and Child & Adolescent Psychiatry, NYU Langone

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00:00Doctor Ledoux his work is
00:02focused on focuses on the brain
00:04mechanisms of memory and emotion.
00:07He is author of several books
00:08including the emotional brain,
00:09the synaptic self, anxious,
00:10and most recently the
00:11deep History of Ourselves,
00:13the 4 billion year story of
00:15how we got conscious brains.
00:16Doctor Ladue has received numerous
00:18awards including the William James Award,
00:20the American Psychological
00:23side from Excuse Me,
00:24the Association for Psychological Science,
00:26the Karl Spencer Lashley Award from the
00:28American Psychological Philosophical Society.
00:30The fission international prize in
00:33cognitive science and many others.
00:35Doctor Do is the fellow of the
00:38American Academy of Arts and Sciences,
00:40the New York Academy of Sciences,
00:41the American Association for
00:43Advancement of Science.
00:44And he is a member of the
00:45National Academy of Sciences,
00:46and he's also a lead singer of the amyloids.
00:51And I think this is the he is
00:53the first actual rock star we've
00:54had give rounds to the center.
00:57So without further ado,
00:58I give you Doctor Ladon.
01:05Thank you very much. Yeah.
01:08So the amygdaloid ads, you know, we.
01:11Play around every now and then,
01:13but during COVID we haven't had many chances,
01:15but hopefully we'll start again.
01:18So today I'm going to talk about what
01:19happened to the middle and middle disorders.
01:24So I'm going to start with kind of giving
01:27you a bookmark of something that happened
01:30and bookmarked this topic by talking about
01:33something that happened in 1917 and 2018.
01:36So in 1917, Freud said there's no question
01:39that the problem with anxiety is a Riddle
01:42whose solution would bound to throw a
01:45floodlight on our whole mental existence.
01:48And in 2018, my colleague Michael
01:51Fanselow and his student Zachary.
01:54Pennington said, returning to an emphasis
01:56on subjective mental experience.
01:58Something I had been arguing for would
02:00put us back well over a century to what
02:03was truly the dark ages of psychiatry.
02:05So that's what I want to talk about,
02:07what's going on in the middle
02:09of these two events.
02:11So here's a very short story,
02:13a version of this story and
02:15of course behaviorist bands,
02:16mental States and psychology.
02:18In the early 20th century,
02:20the mental approach of psychoanalysis
02:22was uninfluenced by all of this,
02:24by behaviorism and thrived in Europe.
02:27And then before and during World War Two,
02:29psychoanalyst mini Jewish fled to
02:31London and the Americas, at the time
02:34the medical model of mental illness,
02:35using medications to treat.
02:37Fighting disease states was emerging to
02:39help psychiatry become more scientific.
02:41That is, less priority and less objective.
02:44But instead of distancing
02:45the feel from Freud,
02:46subjective experience was
02:48generally marginalized.
02:49Some success has resulted from
02:51clinical studies of medications,
02:52but often from incidental findings.
02:55To improve the efficiency of drug discovery,
02:57pharmaceutical companies hired behaviors to
02:59test new medicinal treatments in animals.
03:01The assumption was that mental states
03:03are quaint fictions, and the changing
03:05behavior will make any lingering.
03:07Problem disappear.
03:08And that was the essence
03:11of the fanselow argument.
03:13Now few few efficacious agents
03:16were discovered the after 50
03:19years of disappointing results,
03:20big forma began reducing funding
03:22to find new treatments.
03:24But researchers and universities
03:25equipped with better and better T
03:27techniques like optogenetics and all
03:29sorts of genetic tools persisted in
03:31studies using animal behavior to try
03:33and discover treatments for mental suffering.
03:35Assuming that the magic bullet
03:37bullet was just waiting to be found.
03:39It still doesn't exist in
03:41Mill suffering continues.
03:42So the conclusion of all this
03:44is that people often seek help,
03:46the help of therapists because they
03:48feel bad subjectively drugs based on
03:50animal behavior appropriate for changing
03:52behavioral and physiological symptoms,
03:53but not for treating troubling mental states.
03:56If every change is avoidance
03:58and physiological arousal,
03:59but doesn't help with
04:01the subjective symptoms,
04:02the patient will continue to suffer mentally.
04:04This doesn't mean that Troy was completely
04:06right and behaviors were completely wrong.
04:08Subjective and objective symptoms
04:10must both be treated,
04:12but they depend on.
04:13Different brain circuits and have
04:14to be treated separately now if you
04:16need to go anywhere or leave early,
04:17now would be a time because I've
04:20summarized everything I'm going to say.
04:22But let's get into the details.
04:24So I want to use the science of fear to
04:26illustrate what I see as the problems here.
04:27And I'm not a psychiatrist or a clinician,
04:30so in some ways I have no
04:32business talking about this.
04:33But I'm talking about it from the
04:35perspective of someone who studied
04:36the brain for decades, many decades,
04:38and I'm just going to add my perspective
04:42on what I think might be useful.
04:45Doesn't mean it's completely correct,
04:46but I hope it's useful.
04:48So why is she screaming?
04:51Well, the obvious answer is.
04:56OK, so now everything is out of whack here.
04:59OK, I obviously answered that too.
05:01Why she's screaming is that she's
05:02afraid I have two monitors here.
05:04They're not quite sync, right?
05:07So, but the question is,
05:09is her fear the cause of her screen?
05:12And that is the fundamental
05:14topic I want to address here.
05:15So the main theme of this lecture is
05:18that conflation of subjective experience,
05:20the subjective experience of fear,
05:22with behavioral and physiological correlates
05:24of fear has led to the false premise that
05:27if the objective response are treated,
05:29the mental part will come along for the ride.
05:31So it's a it's a truism, really.
05:34You know that the mental health is first
05:37and foremost about a healthy mind.
05:39If we don't have a healthy mind,
05:40it doesn't matter if our body
05:43is responding properly.
05:44So I want to talk about all this
05:46through my 40 year adventure in
05:48studying emotional consciousness.
05:49And this goes back to my PhD thesis in 1978,
05:53which I studied conscious and unconscious
05:55processing and split brain patients.
05:57So that's me on the left and that's
05:59like the zanaga on the right.
06:01My mentor.
06:03We did a lot of studies
06:06that that were you know,
06:07Mike had been involved in the early
06:09days of Split brain research in the
06:1260s at Caltech with Rogers Barrett and
06:14all the basic kind of findings were
06:16uncovered at that point about you know the.
06:20The If you put information in
06:21the right hemisphere,
06:22the left hand can pull it out of a bag,
06:24but the right can hand can't hand it,
06:27the right can't,
06:27right hand can't pull it out of the bag,
06:30and so on.
06:31But what we wanted to do was ask more
06:34fundamental questions about what does it
06:36mean for the actual living human being,
06:40not just for what are the implications
06:42for understanding split brain patients?
06:44What does it mean for our middle existence
06:47that we can do these dissociations?
06:51Split brain patients.
06:52So we did this one study that
06:54got a lot of a lot of attention.
06:56So the patient,
06:57you know as you probably know
06:59the and split brain patients,
07:01the two hemispheres are separated by
07:04cutting the connections between them
07:06in an effort to relieve intractable
07:09epilepsy and in these patients.
07:12Left the left hemisphere,
07:14typically, as in most people,
07:16has the ability to speak
07:17and comprehend language,
07:18and the right hemisphere has
07:21much more limited capacities.
07:22Doesn't have all of the human equipment,
07:25lacking significant amounts
07:28of language there.
07:30So we had what we did was we put a
07:33stimulus into the left hemisphere.
07:36In other words, the right visual feel,
07:38the chicken claw goes to the left hemisphere.
07:42Left visual field goes to the
07:44right hemisphere.
07:45Just the way the visual system is organized.
07:47If you flash stimulate to the right.
07:50Right it goes to the left hemisphere,
07:52flush to the left it goes to
07:54the right and so.
07:55The left hand immediately
07:56pops out and points to
07:58a shovel in the right hand to the chicken.
08:01So we ask the patient, why did you do that?
08:03Now we're talking to the left
08:05hemisphere because only the left
08:07hemisphere can talk back to us.
08:08So the left Timbers left,
08:10left Hemisphere says. Well, I saw.
08:14I saw chicken claw, so I picked a chicken.
08:17And you need a shovel to
08:19clean out the chicken shed.
08:20So the left hemisphere had no idea why
08:23the left hand had pointed to the shovel,
08:26but it spun a narrative, a tale,
08:29a story that made its behavior makes sense.
08:32So what we concluded from all this was that.
08:35You know, our conscious minds typically
08:38believe that we have free will,
08:40that, you know,
08:40we're in charge of our body and
08:42it's very disturbing if your body
08:44is producing behaviors all the
08:45time that you aren't in charge of.
08:47So in order to protect mental unity,
08:49our idea was that the human brain
08:52developed some kind of capacity
08:54for explaining behavior.
08:56So you, you know,
08:57you say something stupid in a conversation
08:59or in a fight with your spouse,
09:01and you regret it.
09:02And so you, you might at the moment say,
09:04I'm sorry, I should have said that.
09:06Or you might become very defensive
09:08and and try to compensate for it.
09:11But in each case you're getting a new
09:13narrative of the of what you did.
09:16So Mike was a good friend of
09:18Leon Festinger's at the time.
09:20And so we've interpreted all this
09:21in terms of cognitive dissonance,
09:23that it's disturbing.
09:24It's it's dissonance inducing
09:26for your behavior to be produced
09:28in a way that you aren't.
09:29You don't think you're in charge of you,
09:31not that your body did,
09:33but you consciously didn't do and that.
09:36When we spend these narratives,
09:38that's a dissonance reducing
09:40kind of activity, so.
09:46That night we would these these patients
09:48were all at Dartmouth Medical School.
09:50They operate on the Dartmouth and lived up in
09:53the rural areas of Vermont, New Hampshire.
09:55And so we drive up to and then we have
09:59this kind of yellow or pink was orange van
10:02that we pulled a camper trailer behind.
10:05We'd set up a testing lab and and so
10:07we then we go hang out at the bar and
10:09talk about what we had discovered
10:11or or observed during the day.
10:14And we talked about how emotion systems
10:16might be the kinds of systems that
10:19would generate behaviors that demand
10:21these dissonance reducing narratives.
10:24So at that point, Mike said,
10:27you know, there's not much research
10:29on emotion these days.
10:30I said, well, yeah, OK, maybe I'll try that.
10:33And so I decided that, you know, I did,
10:36I wasn't going to have split brain patients
10:38to work with after I left Mikes Lab.
10:40I mean that was his thing, not mine.
10:41And so I had to find something
10:43else to do and I decided that.
10:45But I would work on.
10:47Was the study of.
10:51How these what might be, how these
10:54emotions systems might be generated,
10:56these kinds of behavioral and physiological
10:58responses that might demand this kind
11:01of dissonance reduction activity.
11:03So before I did any research I have
11:05Mike asked me to write a chapter for
11:08this book he was editing and so I wrote
11:11this generated this hypothesis based
11:13on our split brain research about what
11:15how emotion might work in the brain.
11:17So we have an emotional stimulus
11:19goes to a sensory system.
11:21The sensory system feeds into the brain.
11:24It goes to cortical circuits to
11:26generate these conscious feelings
11:28that we have the emotions,
11:29but it goes to subcortical areas to
11:32automatically produce the responses.
11:34Just as in the split brain patient,
11:37you've got these automatic responses
11:39being generated unconsciously.
11:40And then because it's disturbing to you
11:43for these behaviors to be coming out,
11:45you generate a narrative or conscious
11:48interpretation that becomes the
11:49basis of the feeling now.
11:51It was all kind of very poorly
11:53conceived at the time because it was,
11:55you know, I was just making it up.
11:57But this has guided my whole set
12:00of research and and all my books
12:03and so forth over the years.
12:05So the idea was that fear was a
12:08cognitive interpretation or narration,
12:09and the the innate emotional
12:12behaviors and physiological responses
12:14that that come along for the ride
12:17are a different thing altogether.
12:19So I turned to rats to do all of this,
12:22to understand these circuits
12:24that might demand these kinds of
12:26narrative inducing just dissonance,
12:30reducing narratives.
12:32And I used the procedure called
12:33Pavlovian fear conditioning as
12:35a model of emotional behavior.
12:36And I would that's called fear
12:38conditioning because that's been
12:39the assumption of how it works.
12:41I mean,
12:42the behaviors got rid of mental state terms,
12:44sort of mental states,
12:45but they didn't get rid of
12:47mental state terms.
12:48So fear became the relationship
12:50between a stimulus and a response.
12:53It was just a functional relationship.
12:55It had nothing to do with subjectivity
12:58but the rest of the world.
12:59When you call something fear,
13:01thinks you're talking about the
13:03subjective experience of fear.
13:04So that was a bit of a problem.
13:07So but this,
13:08this was an appealing procedure technically,
13:10because you take a simple stimulus
13:13that generates a very reliable
13:16stereotyped response that occurs
13:18in every rat that you tested in,
13:21and it's kind of ideal for tracing
13:24circuits from sensory to motor neurons,
13:26which had been done in invertebrates.
13:29Eric Candell and others were doing that,
13:31but it wasn't really commonly.
13:34Pursued in invertebrates in
13:36mammals because it was thought
13:37that the brain was too complicated.
13:40But you know,
13:40if you have a good stimulus
13:42and a good response,
13:43then you can go a long way
13:45with this kind of stuff.
13:46So I had,
13:47I wrote this NIH NIMH application to study
13:50the Neuropathways of Motion was rejected.
13:53Why?
13:54Because emotion is not
13:56a neuroscientific term,
13:57not neuroscientific topic.
13:59This was 1986,
14:00and it was the behaviors were still very,
14:04very strongly dominating in neuroscience,
14:06as they are today, and in many ways.
14:10So I changed the title to emotional
14:13conditioning and got the brand,
14:14but one of the reviewers said,
14:16well you're studying Pavlovian
14:17conditioning and you don't have
14:19a non associative control group.
14:21So I put the control group in.
14:22That's what it took to get the grant, so.
14:25You know pretty quickly we we were able to
14:29make a lot of progress by we I mean people,
14:33three or four people who were doing this.
14:35Mike Davis who was at Yale at the time
14:37was was there right at the beginning.
14:40I remember this society for neuroscience
14:43meeting in 19 must have been 868586 and
14:47it was me Mike Davis from Yale and Bruce
14:51Cap from the University of Vermont.
14:53And we were the only three people
14:55doing fear conditioning in the brain.
14:57The Society for Neuroscience and for
14:59the for quite some time we were the
15:02main people driving this kind of work.
15:05A bit later fans slow and some
15:07others got involved.
15:08And that the, you know,
15:10within a few years the the core people
15:12who were doing this had generated
15:15a pretty good understanding of how
15:17information gets into the brain,
15:20how it comes out of the brain
15:22and what's in the middle.
15:24And what was in the middle was the amygdala.
15:26It's not like we were.
15:27Looking for the amygdala,
15:29but the stimulus took us there
15:31and the response took us out.
15:33So, you know, so a lot,
15:36a lot was already known in terms of what,
15:38in other words, the what.
15:40Behaviorally,
15:41about all the principles were what
15:43we were able to do was connect
15:45all of the dots in the brain to
15:47put the circuitry together,
15:48and then all these molecule genes
15:50and molecules on the right.
15:52All of them have been identified both
15:55in invertebrates and in vertebrates,
15:58as being important in the plasticity.
16:01So the top part of that is
16:03a presynaptic neuron, say,
16:05coming from the auditory system,
16:06and the bottom part is a postsynaptic
16:09neuron in the amygdala that.
16:10And then then the molecules and the
16:13pre and post synaptic neuron are
16:15being are interacting to generate
16:17the plasticity that will allow the
16:20conditioned stimulus now to get through
16:22the amygdala and produce the responses.
16:25So this all happened,
16:26you know, by the end of.
16:29The 1990s,
16:30all of this was basically known.
16:33So it was like, you know,
16:3410 or 15 years it took to do this,
16:37but that that's a pretty quick
16:39schedule for this kind of work.
16:41So anyway.
16:42I never stopped thinking about and
16:44writing about emotional consciousness.
16:46So in the emotional brain I've
16:48talked about working memory and
16:49emotional consciousness and epic self.
16:51Still on working memory and anxious,
16:53I've kind of shifted to the
16:55global workspace theory.
16:56And then finally in the deep
16:57history of ourselves,
16:58I'd come across the higher order
17:00theory of emotional consciousness.
17:02And that's what I've kind
17:03of adopted and will say
17:04a little bit about towards the end,
17:06if there's time. So.
17:09Plugging the the anatomy that I've
17:12just described to you into the
17:14original model from the early 80s,
17:17what we see is that we've got a,
17:18you know, the,
17:19it's still the cognitive interpretation,
17:21but now I'm adding the prefrontal
17:23cortex into there and freezing.
17:25We can now add the amygdala and
17:27periaqueductal Gray and so forth.
17:29So it, you know, it's useful to have a
17:31kind of conceptual model when you start,
17:33but you have to be willing to throw it away.
17:35But I was fortunate that I didn't
17:36have to throw it away.
17:37It seemed to kind of fill in.
17:39So, but one of the things that I was
17:42explicit about was the difference
17:44between explicit fear and implicit fear.
17:47So I'd always talked about the amygdala
17:49as as being an implicit fear center.
17:52Everybody was talking about
17:53the amygdala fear center.
17:55But I wanted to make it clear that the
17:58amygdala was implicit or unconsciously
18:00detecting and responding to danger,
18:02and that the conscious experience
18:04of fear was the cortical
18:05interpretation of what was going on.
18:07But that distinction.
18:08Did not hold up the way it did in
18:11memory research where it implicit
18:13and explicit is widely accepted.
18:15But you really don't hear a lot about
18:18this distinction in the emotion feel,
18:20especially not in terms of the amygdala
18:23and its so-called role and fear.
18:25So.
18:28This is what I already showed you,
18:29but what I want to emphasize is
18:32this amygdala fear center idea.
18:34I mean the the as I said the the implicit
18:37explicit extinction didn't catch on and.
18:41Everyone was talking about the
18:43amygdala being involved in fear.
18:44I'd be introduced in lectures as
18:46having discovered how feelings of
18:48fear come out of the amygdala,
18:49and that's not what I ever really,
18:51you know, I probably wasn't as clear as I
18:54am today about what I I thought back then,
18:57but because my books were a little
18:58kind of sketchy, sometimes I'd talk
19:00about fear without being clear.
19:03But you know that at some point,
19:06like in 2012 or so, I said, OK,
19:09I really need to make myself.
19:11Clear and say what I'm talking about.
19:14So I wrote this article in Neuron
19:17called rethinking the emotional brain.
19:20But before I get to that,
19:21what's wrong with the amygdala fear center?
19:23Well, first of all,
19:25behavioral physiological responses
19:27don't always correlate strongly
19:28with subjectively experienced fear,
19:31and they should,
19:31if they're all products of fear
19:33in the amygdala, mean Peter Lang,
19:35you know,
19:36involved in anxiety research from
19:38from decades ago in the late 60s,
19:41made this point that the behavioral
19:44and physiological responses don't
19:46always correlate with subjective fear.
19:49And #2 non consciously processed threats,
19:52for example if you subliminally present
19:55stimuli like with visual masking,
19:57or if you're starting a patient
20:00with blind side.
20:02Stimulus will go into the brain
20:03and for your image, the brain,
20:05the amygdala will be activated.
20:07The responses will be generated.
20:10But the person or patient,
20:12depending on the situation,
20:13will not report any fear and not even be
20:17able to tell you what the stimulus was.
20:19So if the amygdala,
20:21if the person is not experiencing
20:23fear but the amygdala,
20:25is active in generating these responses,
20:27fear is not the source of those responses.
20:30It's a separate thing.
20:31And damage to the amygdala can interfere
20:33with the ability of threats to elicit
20:35behavioral and physiological responses,
20:37but doesn't necessarily eliminate
20:39the feeling of fear it should,
20:41if that's where the fear is coming from.
20:43So you know, neuroscientists can explain
20:45fear conditioning in terms of system,
20:47cells, synapses and molecules.
20:49This logic works fine.
20:51And invertebrates like ephesia or
20:53flies and so on. And vertebrates,
20:56so mammals, humans, everybody.
20:58No need to call upon concepts such as fear.
21:02All you need is heavy.
21:03And plasticity like CS is a weak stimulus.
21:06the US is a strong stimulus.
21:08They come.
21:09The two stimuli come together
21:11on neurons in the amygdala.
21:12The strong stimulus causes a change
21:14in the neuron that allows the
21:17weak stimulus to be synaptically
21:19connected with the same neuron,
21:21and this week stimulus can then go
21:23into the brain and more effectively
21:26activate those neurons to produce
21:29the responses.
21:30And if you have a neuromodulator
21:32like norepinephrine being triggered
21:33by the unconditioned stimulus,
21:35the shockers as we know, as in case.
21:39Then that neuromodulator will
21:41potentiate the plasticity and also make
21:44the responses stronger.
21:46So it's not that, you know,
21:48fear is a meaningless concept or construct,
21:51it's just that it's not what's
21:53involved in explaining these kinds
21:55of simple behavioral paradigms.
21:57So it's and that you know, it doesn't,
22:01it doesn't help us to over interpret
22:04what we're talking about or what
22:06we're seeing for the sake of well,
22:10I'll talk about that later.
22:11So I wrote this paper rethinking
22:13the emotional burden.
22:13So the basic idea, this is the,
22:15the classic idea since the stimulus
22:17activates fear in the amygdala
22:19and fear controls the behavior.
22:21And I said, well,
22:22let's get rid of that and instead talk about.
22:25What the amygdala does,
22:26or what's going on in the amygdala
22:28in these situations of danger,
22:29is a defensive survival circuit,
22:32activity set of activities that
22:35the stimulus will activate,
22:37either because it's an innate stimulus
22:39like a snake or something like that,
22:41or condition stimulus.
22:42The survival circuit will then be activated
22:45and behavioral and physiological responses,
22:48defensive responses that are
22:50part of your survival activity,
22:52survival protection,
22:53and the presence of danger.
22:56Will be activated automatically
22:58because these circuits are innate.
23:01And again, it could be activated by an
23:03innate stimulus or condition stimulus,
23:05but the if the responses
23:07are pretty much innate,
23:09so you don't need the actual
23:11subjective experience of fear,
23:12you just need a circuit that can
23:14detect and respond to danger. So.
23:16Why does it matter what we call things?
23:19Well, there are lots of reasons,
23:21and I'll just give you 4
23:23here quotes from four people.
23:25Francis Bacon in 1620 said scientists
23:28should be vigilant and guard against
23:30tacitly granting reality to things.
23:32Simply cook because we have words for them.
23:34George Mandler and William Kesson and a
23:36book called the Language of Psychology.
23:38It's it's a very interesting book.
23:40In 1964 the common language is full
23:42of quasi psychological assertions
23:44and the language in which these
23:46are framed is inadequate.
23:48Jack Block was a personality psychologist
23:50at the end of his career in 1995.
23:52He said psychologists have
23:54tended to be sloppy with words,
23:55summary labels and shorthand ideas
23:57come to control the way we think.
24:00He also said that we should be more
24:02become more familiar with things
24:04denotatively and connotatively
24:06to make ourselves clear,
24:08and not just use kind of concrete
24:11bized words that we've passed
24:13on from generation to generation
24:15and assume that it's simply that
24:17the word has the meaning that it
24:20had 25 or 30 or 100 years ago.
24:22Melvin Marks there's a semantic day in 1951.
24:25Marx was a a behaviorist,
24:27and he's talking about the the behaviorist
24:31tendency to use these mental state terms,
24:34like for fear but not to mean fear.
24:37What they meant was that there's some
24:39kind of intervening variable that was
24:41psychological but not necessarily subjective,
24:44that connected the stimulus and the response,
24:46but they didn't care about
24:47what was in the brain.
24:48But,
24:48Marks pointed out,
24:49there's a semantic danger that results
24:51when a common language.
24:52Term is used as a scientific
24:54name for an intervening variable
24:56or hypothetical construct.
24:58The variable of construct becomes
25:00infected with the subjective
25:02properties of the common meaning.
25:04So in psychology and neuroscience we
25:06have unique conceptual challenges.
25:08So biologists call a family of genes
25:10hedgehog because of some feature
25:11physical features of the gene.
25:13But no one in biology believes
25:15the gene has anything to do
25:16with the animal called Hedgehog.
25:18But when we use a word like fear,
25:20there's assumption is subject
25:21matter is our everyday experience
25:23of fear when in danger.
25:25And so again like Mark said,
25:27the circuits,
25:28the behaviors get infected with the
25:31subjective meaning that the word carries.
25:34So here's some examples of
25:36where we get into trouble.
25:38So David Anderson is one of the most
25:41prominent neurobiologists in the world.
25:42He studies flies,
25:43and he's gotten interested in
25:45in the emotional state of flies.
25:47And he says an emotional state,
25:49possibly analogous to fear and
25:50mammals lies between the threat
25:52and freezing behavior and flies.
25:54By studying flies,
25:55we can learn important things
25:57about human emotions now.
25:59Anderson was not talking about
26:01the subjective experience, but.
26:04Headlines.
26:04Flies have feelings, fear,
26:07and maybe more.
26:08Flies experience emotions like
26:09fear and maybe offer insights
26:11into how the brain makes feelings.
26:13So,
26:13you know.
26:14It's we have to be careful how we
26:17talk about things because if we use,
26:20I'm not saying we should never
26:22use common language terms,
26:23but we have to be clear what we mean by
26:25those terms and not over interpret them.
26:28Because the meaning that you imply
26:30or think you're implying is not
26:33necessarily the one that's going
26:34to go out into the public and these
26:37ideas go into the public and then
26:39actually come back into science
26:41and become part of the science.
26:43So it's a problem. We have to be clear.
26:45About what we mean as as Jack Black said,
26:48Denotatively and Connotatively,
26:50what do these words that we use to
26:53describe brain circuits and behaviors mean?
26:56Here's another one from Louisiana.
26:58So we call these things
27:00crawfish rather than crayfish.
27:01Crawfish treated with a
27:03benzodiazepine with more exploratory,
27:04less inhibited in a chamber in
27:06which they received electric shock.
27:08I mean, did this belong in science?
27:10I don't know.
27:11This is perfectly fine set of findings,
27:13but it's not that, you know,
27:14insightful, but why was it published?
27:17Well,
27:18science had the headline anxious
27:19crawfish can be treated like humans.
27:21York Times,
27:22even crawfish get anxious and BBC
27:24crawfish may experience. Of anxiety.
27:27No more sedate version of that.
27:30So you know a practical example of
27:33why words matter if we consider
27:37anxiety anxiolytic drug development.
27:39So how do you develop a drug?
27:41So I handed it this early.
27:43You take animals and you studied
27:45their defensive behaviors and you
27:48assume that they're going to measure
27:50some brain state of fear or anxiety.
27:53So a drug that's given to.
27:56The animal of the drug company
27:58that alters the defensive behaviors assumed
28:01to change this brain state of fear anxiety
28:03by targeting a fear or anxiety circuit.
28:07And because humans have inherited this
28:08circuit from the million ancestors,
28:10giving the drug to humans to change
28:12the brain state and make people
28:14feel less fearful or anxious.
28:15So in 2010, and we really Class
28:19CEO Glasgow Smith Kline concluded
28:20that the effort has failed and new
28:23investments would not be made because
28:24of the low probability of success.
28:26Andrew Holmes, a leading researcher,
28:28reached a similar conclusion.
28:29These efforts have been disappointing.
28:31It's promising results with novel
28:33agents and rodent studies very rarely
28:35translated into effectiveness in humans.
28:37Eric Nestler and Steve ***** 2 very
28:40prominent biological psychiatrist,
28:42said they echoed the sentiment,
28:44saying that the molecular targets
28:46of current major classes of
28:48psychotherapeutics were all reverse
28:50engineered and animal studies from
28:52drugs discovered incidentally prior
28:54to 1960 by clinical observation.
28:56So nothing new has really been
28:58discovered because the same thing has
29:00been searched for over and over again.
29:02So yeah,
29:03the effort continues because of a commitment
29:05to a poorly conceived set of constructs,
29:08both psychologically and psychiatrically.
29:10So psychologically,
29:12the assumption is that mental states
29:13of fear can be measured by innate or
29:15conditioned behaviors in animals and people.
29:17And you see this not only
29:19in the animal research,
29:20but also in human research where you
29:23show people pictures of, you know,
29:26snakes or other kinds of threatening stimuli,
29:28or you show them faces of aggressive
29:31or fearful.
29:32People.
29:33People with expressing fear or
29:35are aggression in their faces,
29:38and you're assuming that this is
29:40activating a fear center in the
29:42amygdala and that this is going to
29:45be measurable in by using galvanic
29:47skin response or something like that.
29:50But I don't think that's really
29:52going to help.
29:53Psychiatrically,
29:53pathological fear is assumed to
29:55be a product of a malfunctioning
29:57genetically wired fear circuit,
29:58and the delivery of the right chemical to
30:01this first circuit will fix the problem.
30:03So here are two scenarios in social anxiety.
30:06The fear anxiety scenario.
30:08The medical medication will
30:09turn off your fear center.
30:10You'll be able to go to the party
30:13and not feel afraid or anxious.
30:15This is what everyone hopes will happen,
30:17but it's not really what happens.
30:19The physiological symptom scenario,
30:21the medication effects systems that
30:23control behavioral and physiological
30:25responses and challenging situations,
30:27we find it easier to go to the party.
30:28You'll be less avoidant and
30:30less jittery or less aroused.
30:32And while you probably still feel anxious,
30:34I mean,
30:34you've been anxious all your
30:35life and you're probably still
30:36going to be a little anxious.
30:37You'll be better able to cope with
30:39the threatening situation and can
30:40use it as a way to become physically
30:42more comfortable being there.
30:43It's not a cure,
30:44but it might help you cope
30:45with your symptoms.
30:46I mean,
30:46I think you'll have to agree
30:48that the second one is the more
30:50reasonable thing to tell the
30:51patient, because it's more based on what
30:54the research from the animal animals
30:56from the animal lab has really told
30:58us about his behavior and Physiology.
31:01We can't understand the mental states
31:03of humans by studying rat behavior.
31:08So here we go,
31:09back to the defensive survival circuit.
31:11The drugs are developed using these
31:14defensive survival behaviors, right?
31:16So they're based on these survival circuits,
31:20but if people are feeling fearful and
31:24anxious because they're cognitively
31:26interpreting their situations in this way,
31:29then you know, it's not surprising that
31:32the medications are not working as well.
31:34So a typical behaviors account
31:36works fine sub cortically like that,
31:38but we need something more elaborate,
31:41more human like, to understand what's
31:43going on in the middle states of people.
31:48So, you know, critic might say that,
31:50well, some medications used to
31:51treat for anxiety sometimes too
31:53effective some subjective feelings,
31:55for example, benzodiazepines,
31:56they often make people feel a little better.
31:59But we have to ask whether the effects
32:01are truly accounted for by reduction
32:03in fear or anxiety or from up by other
32:05factors that change the feeling somewhat,
32:07but for reason reasons other than
32:09specifically affecting fear anxiety.
32:11If we're going to find new medications,
32:13we've got to, you know,
32:15really understand why a medication works.
32:18Right.
32:18We can't just say, well,
32:20and in general it works.
32:21We have to know something much more specific.
32:24So, you know,
32:25here's some reasons why a benzo might
32:28make someone feel a little bit of
32:30a blunting of emotion in general.
32:31A lot of therapists have told me,
32:33psychiatrist and psychotherapist
32:34have told me that's what they think.
32:36Benzos are basically doing #2 indirect
32:40effects on feelings caused by reducing
32:43feedback from body responses and
32:45physiological arousal in the brain.
32:47So it's, you know, when you.
32:48We're getting all these,
32:50these physiological symptoms turned down.
32:52That will help a bit.
32:53But I think it's kind of like,
32:55you know,
32:55if you go to a bar restaurant
32:57and let's say it's a restaurant
32:59and the music is too loud,
33:01they're playing some awful heavy
33:02metal music and you don't like it,
33:03and you ask the waiter to turn it down,
33:05they turn the volume down on the song,
33:08but it's the same annoying song.
33:10It's just not quite as annoying
33:12because the volume is lowered.
33:14And I think that this can be something that
33:17the medications might be really useful for.
33:19Lowering the volume and then
33:22the the third reason is.
33:24That the effects are due to
33:27altering cognitive processes,
33:28the constructor motions like memory,
33:30attention, working memory,
33:32self processing and so forth.
33:35Then so the the reset GABA receptors
33:37are throughout the brain and every
33:40part of the brain literally.
33:41So you're going to affect a lot of
33:44different circuits and we can't just
33:46assume that there's because it's a
33:49a GABA receptor that binds them to
33:51benzodiazepines that that is only working in.
33:54Fear,
33:55anxiety circuit,
33:55obviously there are lots of side effects.
33:58So that that alone shows that
33:59the stuff is happening all over
34:01the brain and there are cognitive
34:04effects of benzodiazepine.
34:05So you know we have to just kind
34:07of ask what it is that we're
34:10really getting out of these
34:12medications because if we don't then
34:14we can't go forward and that's why you
34:17keep rediscovering benzodiazepines
34:18and and reuptake inhibitors because
34:20that's what you're looking for.
34:24So we need a conceptualization of
34:26fear and anxiety that recognizes
34:28the importance of innate.
34:30Make condition circuits sorry innate
34:32and conditioned circuits that
34:34have been inherited from animals,
34:36but one that doesn't confuse those
34:37circuits with circuits that underlie
34:39conscious feelings of fear or anxiety.
34:41So I want to now switch to
34:43what exactly I think is going
34:46on in emotional consciousness.
34:48So the hypothesis that I've been
34:50working with for a while now is that the
34:53brain mechanisms underlying emotional
34:54states of consciousness are not that
34:56different from those underlying any
34:58other kind of state of awareness.
34:59In other words, we have one.
35:01Kind of emotion,
35:02one kind of consciousness
35:04system in the brain and.
35:06What that system is processing
35:08is what you're conscious of.
35:10So what's different about emotional
35:12and non emotional experiences and
35:14what's different about different
35:16kinds of emotional experiences in
35:19this idea are the inputs processed by
35:22higher cortical cognitive network.
35:23So these would involve,
35:24you know, prefrontal cortex,
35:26parietal cortex,
35:27all these kind of higher cognitive circuits.
35:32So rather than having different
35:34subcortical circuits for different
35:35emotions as in basic emotions theory,
35:37which is, you know,
35:38all these different emotion circuits
35:40like the amygdala does this,
35:41the periaqueductal Greg does that.
35:44Hypothalamus does this.
35:46This higher order circuit idea is that
35:48we have these higher order cognitive
35:51representations of redescription or
35:53indexes or whatever you want to call them,
35:55that account for emotional and non
35:58emotional experiences in one system.
36:00So the idea is that the information
36:02being processed by this higher order
36:04circuit is different in emotional and
36:05non emotional situations and different
36:07and different kinds of emotional situations.
36:10So I don't believe in basic emotions.
36:12For me all emotions are
36:14cognitive interpretations.
36:15I'll explain that more in a minute.
36:18So here's, you know,
36:19basic idea.
36:19You've got water, onions,
36:21garlic, celery, salt,
36:22pepper through all that stuff into a pot.
36:25And none of these are super ingredients,
36:28right?
36:28But somehow if you now throw some chicken in,
36:31it becomes chicken soup.
36:32And again,
36:33chicken is not a soup ingredient either.
36:35None of these things exist for the
36:37purpose of making soup with soup.
36:39Flavor of the Super emerges from all this,
36:42and I think we can say the
36:43same thing about making fear.
36:45It's there are No Fear ingredients
36:47in the brain.
36:48Fear is the cognitive interpretation that
36:50is based on all these kinds of processes
36:53that that are generic processes really.
36:58So let's put it in a different picture.
37:00So.
37:01The blue part there is basically
37:05working memory.
37:07And the idea is that within working
37:09memory we assemble a mental model of
37:12fear or love or any other emotion
37:14that we're going to experience.
37:16And we do this by monitoring, appraising,
37:19attending to all of these inputs.
37:22This allows us to have
37:23metacognition is about,
37:24in other words,
37:25thoughts about what's going on.
37:27We can introspect about it,
37:28give verbal reports and control,
37:30goal directed.
37:31Behavior through this mental model.
37:33So what are the ingredients
37:34that go into that?
37:35Well, start over here on the left,
37:38like 9:00 o'clock we have sensory processing
37:41with sensory processing by itself is
37:43meaningless until you have some memory.
37:46You don't come into the world
37:47knowing what apples, chairs,
37:48light bulbs and so forth are.
37:52You have to add semantic memory
37:54to sensory processing in order to
37:56make that a meaningful perception.
37:58And so semantic memory is a key factor that.
38:01Makes sensory processing go beyond just what
38:04the stimulus is brought into the brain is.
38:07So, but we can also have memories of
38:09the past episodes of our life in which
38:12those semantic situations have occurred,
38:16and this allows us to bring
38:18ourself into the experience.
38:20Now all of these kinds of ingredients are.
38:26Could be part of any kind of situation,
38:28any kind of conscious occurs.
38:30There's nothing to do with the motion.
38:32When we go to the other side of the the,
38:35the emotion plot there and again we
38:38can start it at 3:00 o'clock and go up.
38:41So one of the things that often happens is,
38:44let's say in the case of fear,
38:45we have a survival circuit that's activated.
38:48This is going to produce behavioral
38:51responses that will produce body
38:53signals that feedback to the brain.
38:56It will.
38:58The survival circuit will also
39:00activate brain arousal circuits
39:02that make brain hyper aroused.
39:05But an important thing is the emotion scheme.
39:08Emotion schema are bodies of knowledge
39:11that you've acquired about emotions.
39:14We, you know, we have emotion labels.
39:16We learn about emotion and
39:17we assign words to them.
39:19You know,
39:20you don't have to have the
39:22word to have an emotion,
39:23but you have to have the word to
39:26have the emotion named by the word.
39:28I can say that again if it's not clear, but.
39:30Ask me again if it's not clear.
39:34So schema are these bodies of
39:36knowledge that are particular to
39:38you because you are the person who
39:41have learned what danger is to you,
39:43what fear is to you,
39:45what it what you how you want to
39:47respond when you're in danger,
39:48how you're expected to respond,
39:51how other people respond,
39:52and so on.
39:53It's a catalog of things that
39:56can be activated by a simple
39:58stimulus of snake on the ground
40:00or a mugger coming towards you.
40:03Anything that.
40:04It's a classic elicitor of fear is
40:07going to activate enough information
40:09about the fear schema to unpack
40:12it to basically pattern complete
40:14the experience of fear and as.
40:17And this is not something that just happens,
40:20it's slowly evolves and microseconds or
40:23milliseconds as the episode unfolds so
40:25you find yourself in front of a snake.
40:28You know that snakes are reptiles,
40:30but that's not where your mind goes.
40:31Your mind goes to that.
40:32Snakes are dangerous and they
40:34can bite you and kill you.
40:36So as soon as you are now you've
40:39you pattern completed fear.
40:42But now you start to worry
40:44about what that thing
40:45is going to do to you and what might be the
40:48consequences of being bitten by a snake.
40:50Will you be able to find a doctor?
40:52Will they have the anecdote? And so on.
40:54What will happen to your family if you die?
40:56So fear instantly.
40:58Dwarfs and anxiety.
41:00And then you can go the other way as well.
41:02So if you're anxious about something,
41:04you start to see triggers of fear
41:07all over the environment, right?
41:09Particular stimuli now will trigger
41:11you to be afraid of that stimulus,
41:14because you have activated your brain in
41:16a way that makes those things stand up.
41:20So fear and anxiety kind of
41:21both morph into each other.
41:25But all of this is very particular to you,
41:28because it's your brain that is picking
41:29all this up out of the environment.
41:31Things that are dangerous to me,
41:33you're not dangerous to use, and so on.
41:36So. Umm. All right, now,
41:41one of the reasons we need this kind of view
41:45of fear and emotion in general is because.
41:48You know the the whole idea of the
41:50amygdala fear center is based on this
41:52I they basically what the amygdala is,
41:55is to the extent that it's involved in
41:57danger, it's a predatory defense circuit.
42:00It evolved for mammals to
42:02deal with predators. And.
42:06But not everything that we are afraid of
42:09or anxious about starts with the predator.
42:12I mean, we can have all kinds
42:13of fears and anxiety.
42:15So you're stuck on a mountain top
42:17and you've dropped your backpack
42:18off the Cliff accidentally.
42:20So you know you start to be afraid or anxious
42:24about the fact that you don't have shelter,
42:28food, and water.
42:29So you're afraid that you might die of
42:32starvation or dehydration or hypothermia.
42:35You could be.
42:36Afraid of something that
42:37you hear in a conversation,
42:39or anxious about something you hear
42:42someone incidentally say about you that
42:44they didn't realize you were there.
42:45We we can have fear and anxiety from
42:48endless number of reasons in life.
42:51So it has something sometimes to do
42:53with this predatory defense circuit.
42:55But it's a predatory defense
42:57circuit is not the answer.
42:59And that's why it's it's really all about
43:02the cognitive interpretation of the
43:03situation because that is the the what.
43:06You are your what your brain is
43:08concluding as a result of this pattern
43:11completion of stuff that you've
43:13experienced in the past and giving you
43:16a perspective on what's happening now.
43:18So here's the conceptual hypothesis.
43:21So you have a physical or social
43:23threat in the environment.
43:25It goes into a sensory system.
43:28This is all non conscious processing.
43:30Sensory system can contribute
43:32to the mental model there if you
43:35just go straight through.
43:36But it also activates the threat.
43:38The threat detector generates
43:40behavioral and physiological responses
43:42that contribute to the mental model
43:44and the kind of body feedback way,
43:46but also the brain arousal.
43:49The threat detector will contribute
43:50to the mental model.
43:52But the century stimulus becomes meaningful
43:54when it's combined with memory on top.
43:57There sensory memory
43:59interactions create perceptions,
44:01perceptions and memory combine in
44:04schema to activate to pattern.
44:07Complete the schema and give you
44:09a template for your mental model.
44:11Now your mental model of the
44:14experience is preconscious.
44:16So we've got this completely unconscious
44:18processing then some pre conscious
44:20processing because everything.
44:22Every conscious state.
44:24Is preconscious before it's conscious, right?
44:27Because you don't just.
44:29Have a conscious state.
44:31There's a lot of cognitive processing
44:33that underlies each conscious experience.
44:35So the mental model is pre conscious now.
44:39Here's my we're going back to
44:41the split brain now because.
44:44This is where I started,
44:45that there's some kind of narration
44:48that is generated unconsciously
44:50that then explains what's going on.
44:53So the idea is that we have
44:55this pre conscious narration
44:57coming out of the middle model.
44:59That underlies the conscious experience,
45:02but there's some details that
45:05that's often not understood.
45:07And this is just stuff that I've kind
45:09of uncovered myself in the process of
45:12writing this new book that I just finished.
45:15But the idea is that.
45:17The preconscious narrative.
45:19Can control your behavior,
45:21your goal directed behavior,
45:23and allow you to give a verbal report, but.
45:26Those two things are going to
45:29involve separate neuropathways,
45:31verbal report coming out of language,
45:34areas of the brain,
45:35our goal directed behavior coming
45:37out of straight and so forth.
45:40So you're going to have additional
45:42processing in those circuits that are
45:44going to make the verbal report not
45:46necessarily completely overlapping
45:47with the goal directed behavior.
45:49So you might.
45:50You know, say things that are
45:52different from what you do,
45:53or the things you do are different
45:55from what you say somewhat.
45:56They can overlap,
45:57but they can also diverge,
45:59but there's more because.
46:02Once you're conscious of all this,
46:05the narration is giving you
46:08something to interpret.
46:09You can now.
46:12Also give a verbal report and
46:15control behavior consciously.
46:18So it's not that all of this stuff
46:20is just unconscious.
46:21Once you're conscious,
46:22that opens up a whole nother level
46:24of decision making and control.
46:26So I think one of the reasons that
46:29consciousness is so hard to to
46:31study and understand that because
46:33we never know in an experiment.
46:36Whether the subject is reporting.
46:40Nonverbally when you ask for a
46:42verbal report or are consciously
46:44reporting non consciously or
46:46consciously or whether their
46:48behavior that they choose to perform.
46:50Is gold directed and being directed
46:53unconsciously or consciously?
46:55So I think this, you know,
46:58if you could say, well,
47:00that really complicates things.
47:01It does.
47:02But if you know what the problem,
47:03if you know what the complications are,
47:05they can become a feature rather
47:07than an impediment to understanding.
47:12So this is this is the puts it what I just
47:17said into a slightly different framework but.
47:21On the bottom right there you have a
47:23bunch of different kinds of systems
47:26that contribute to the mental,
47:28the unconscious mental model.
47:30They have sensory, perceptual information,
47:32memory information, goal information,
47:34homeostatic information and
47:35and lots of other things.
47:38So these things are all coming into the
47:40mental model unconsciously and they
47:42are the basis of this non conscious
47:45mental model which spawns 3 tributaries.
47:48One is the tributary of
47:50Goal directed behavior.
47:52One is the tributary of speech
47:54and writing and the last one is
47:57the tributary of Consciousness.
47:59So the tributary consciousness
48:00creates the non sorry.
48:02The tribute of conscious predates
48:04the conscious mental model.
48:05So it's a second mental model that you have.
48:08And once you have that model then
48:11you can also control speech and
48:13writing and goal directed behavior.
48:16So it's just restating what I said
48:18but in a different way graphically.
48:21OK so I just want to briefly
48:24mention see what time of this.
48:26OK,
48:26just want to briefly mention the
48:29higher order theory of consciousness
48:30because I find this a very useful
48:33way for thinking about all of this.
48:35So the traditional view of
48:38higher order theory is.
48:41And most most research
48:42on consciousness in fact,
48:43is about sensory cortex and dorsolateral
48:47prefrontal cortex that is the the main.
48:52At the main kind of interaction
48:54that is often talked about,
48:56that's because a lot of the research
48:59involves sensory processing and so forth.
49:01But I think that the higher order
49:04theory can really benefit from a
49:07more elaborate anatomical framework
49:09because rather than asking how
49:11does a a lower order state.
49:14Become conscious.
49:14What I tried to do with what I'm about
49:18to show you is assume that prefrontal
49:21cortex has something to do with all this.
49:25And work backwards to what are the
49:27inputs to these prefrontal circuits
49:29that might shape our our understanding
49:32of of what those circuits do.
49:35So this is the framework that I
49:37like to work with. So we have.
49:43And you see my cursor on this. Yeah. OK.
49:45So from higher order it what prefrontal
49:48cortex has granular components and what
49:51we'll call sub granular components.
49:53So let's look at the bottom here.
49:55So here's the the granular prefrontal
49:57cortex and I think this now my hypothesis
50:01is this is responsible for the middle model,
50:04but the schematic information is coming
50:08from these sub granular areas like
50:11the ventromedial prefrontal cortex.
50:13The anterior cingulate are the what?
50:16The more general medial prefrontal cortex,
50:18orbital frontal cortex.
50:20These are our areas that connect with
50:23memory systems and allow semantic and
50:26episodic memory to generate schema and
50:29the schema then become the basis for
50:31the granular prefrontal mental model.
50:35So if we work backwards from here,
50:37we see that.
50:38That the representation on top is
50:42very sparse in terms of explaining
50:45complex mental states.
50:47And in general, you know,
50:48all this research on consciousness
50:51in the perceptual system is highly
50:54limiting because what it focuses on
50:57is like dots or lines on a screen,
51:00and whether you perceive them or
51:02can you see this or not,
51:04but our life experiences are
51:05all multimodal and we have to.
51:07Always we are.
51:08Always integrating what is there in
51:10the world with our perceptions and our
51:13past memories and our understanding
51:15of the world and our schema.
51:17Those are the mechanisms that interpret
51:19who we are and what's going on in our lives.
51:22And we we can't understand that
51:25from a simple visual cortex and
51:27prefrontal cortex framework.
51:29But I think we can go pretty far with
51:32the with this as a starting point
51:34where we just begin to appreciate
51:36the complexity of the way the
51:38brain puts all this together.
51:40So these are just illustrating the
51:44the granular prefrontal cortex in
51:46the in the lateral cortex there.
51:49So dorsolateral Pat Goldman,
51:51Rakesh put that on the map in terms
51:54of working memory and so forth.
51:56We have ventral ventral lateral paths lab,
52:00Liz Romanski,
52:01who was my graduate student or
52:03postdoc with Pat, she and Pat.
52:05Put ventrolateral on the map
52:07as being important for auditory
52:09working memory and so forth.
52:12Then we have the arbiter frontal cortex,
52:14lateral orbital frontal cortex,
52:15but I think one of the most important
52:19and under underappreciated structures
52:21is the frontal pole and I'll tell
52:23you why that's important in a minute.
52:25And then on the medial side we have
52:27some granular cortex in the dorsal
52:29medial and the medial frontal pole
52:32and then the lighter Gray areas
52:33are all the sub granular areas
52:36like anterior cingulate.
52:37Prelimbic our medial orbital and
52:40ventromedial prefrontal cortex.
52:42Now the reason these are important
52:44to distinguish is that Umm,
52:46the granular cortex has an
52:48architecture that allows human
52:50cognition to unfold the way it does,
52:53whereas the sub granular cortex is
52:56less complex in that and doesn't
53:00have that particular architecture.
53:02So lateral prefrontal cortex is involved
53:06in working memory cognitive control.
53:08However,
53:08their representations higher order indexing,
53:10global broadcasting and so
53:12forth and and the medial areas
53:14are in memory integration,
53:16schema assembly, self processing,
53:19default mode processing.
53:21But we need more recognition of the the
53:24distinction than than this often used
53:27at least in the consciousness view.
53:29And this is a a kind of
53:30way to think about it,
53:32that you have these lower order
53:35states that have recurrent
53:37networks between all of their.
53:38Various interconnections,
53:40but there are also recurrent
53:42interconnections between the the sub
53:45granular prefrontal and the bottom
53:46and the granular on top and between
53:49the various components of granular
53:50and sub granular and so forth.
53:52So there's a lot that's going on that
53:55if we understand the anatomy better
53:57and build it into the way we talk
54:00about all these things more thoroughly,
54:02I think we would make more
54:04progress on all this.
54:05So let me just close with
54:08emphasized by emphasizing.
54:09What's going on here?
54:11So let's start with the the
54:13light Gray on the right side.
54:16Area, so anterior, cingulate, medial,
54:18prefrontal, that's prelimbic,
54:20ventromedial and so forth.
54:22Media, larval,
54:23these light Gray areas are
54:25all the sub granular areas.
54:27The reason that's important is because
54:29all mammals have those areas, so.
54:33The darker Gray areas are
54:35all primate unique areas.
54:37So you don't have a dorsal medial or medial,
54:40medial, frontal pole or lateral frontal pole,
54:43dorsal lateral or ventral lateral in
54:45rats and and other non primate mammals,
54:48but you have them in in primates.
54:51And in the human brain we have an area,
54:53the a component of the lateral frontal pole,
54:56that is only present in the human brain.
54:58So.
55:00Let's just for the sake of argument,
55:02say that.
55:04The human unique.
55:06Frontal pole has an important role in
55:09human unique kinds of consciousness just
55:12for the sake of argument and that we.
55:16The primate unique areas of the the.
55:20Primate brain.
55:21Are going to be the responsible
55:24for kinds of consciousness that
55:26are shared by all primates,
55:27including humans and including
55:29monkeys and chimps and so forth.
55:32And the Gray,
55:33light Gray areas,
55:35sub granular areas are going to be
55:37the kinds of consciousness that might
55:40be shared throughout all mammals.
55:43So even if we only,
55:45let's just start with the the sub granular.
55:49So there's a lot of concern
55:51about how do we get from human,
55:53how do we get from animal
55:55consciousness to human consciousness?
55:56Well,
55:56if these sub granular areas are
55:59involved in a kind of consciousness
56:01in mammals and all mammals,
56:04then we have a foundation for saying
56:07how did the dorsolateral ventrolateral
56:10evolve in primates from these.
56:14Other kinds of areas that are shared
56:17by all mammals and how did the human?
56:21Prefrontal cortex evolve from the
56:24monkey and other primate prefrontal cortex.
56:27So it's a framework for kind
56:29of starting with what we know.
56:30The idea is that if we knew more
56:32about what the human specific
56:34part of the frontal poll does
56:35for human consciousness.
56:37What the?
56:40What the primate kinds of areas,
56:43dorsolateral, ventrolateral,
56:44and so forth, do for human consciousness,
56:47and what the medial prefrontal
56:49areas do for human consciousness.
56:50We could then try to reverse engineer
56:53what's going on in the brains of other
56:56primates from the areas that we share
56:58with primates and what's going on in the
57:00brains of other mammals on the basis of
57:02what we share with other mammals because.
57:06You know, basically just study consciousness.
57:09Verbal report is almost essential.
57:12Because it's not that because language
57:15is necessary for consciousness,
57:17but it provides an important
57:20leverage point so I can respond.
57:24To something that I'm conscious of
57:26verbally by telling you what's there,
57:28or by pointing.
57:30But if I'm unconscious of something,
57:33I can only respond nonverbally,
57:36pointing or other things.
57:39So in humans, we have verbal report
57:43to separate to give us a clue.
57:45When something is conscious
57:46doesn't mean it's perfect,
57:48but it gives us a kind of way to
57:51we can't talk about things that
57:53we aren't conscious of, right?
57:55So I mean, we can.
57:59Pull things out and so forth,
58:00but I don't want to get into that.
58:03Just want to keep it simple and say that.
58:05That in an experiment.
58:07When you are able to verbal
58:09report about something,
58:11that is the best evidence that the person is
58:15conscious of what they are are experiencing.
58:18So in animals having only
58:21nonverbal responses,
58:22we don't have that way to leverage it.
58:25So I think instead of like trying to to use
58:28simple behavioral responses like other words,
58:31extrapolation from analogy with
58:33human behavior to try to understand
58:37what's going on when a rat freezes.
58:39We we say,
58:40OK,
58:40it's afraid because we're afraid
58:42when we freeze.
58:43But this extrapolation from from human
58:46behavior I think gets us into trouble.
58:49We need a different way to approach it.
58:51I think this anatomical approach of
58:53reverse engineering based on what
58:55we learn about human consciousness
58:57might tell us more about what might
58:59be going on in in other mammals.
59:01OK, So what is an emotion?
59:02It's a mental model based,
59:03narrative driven,
59:05culturally shaped,
59:06subjective experience and biologically or
59:09psychologically significant situation.
59:11All humans must deal with danger,
59:13and all cultures have words for
59:15danger and words for experiences
59:16that occur when in danger.
59:18But emotional experiences
59:19vary across culture.
59:21Because we can translate words
59:22like fear across cultures,
59:23we assume that people in these cultures have
59:25the same basic experience named by the word.
59:28But cultural differences and experiences are
59:30based on differences in the schema involved,
59:32that is the schema or personal.
59:34So the different people within
59:36a culture have different schema
59:37and hence different experiences
59:39and people in different cultures.
59:41We also have different schema
59:43and different experiences.
59:44Other animals,
59:45lacking our specific kind of
59:46cognition and brain,
59:47can't have our kind of schema
59:49and our kind of fear.
59:50But they may have their own emotions
59:52made possible by their own brains.
59:54So she's screaming and she's
59:56afraid that these are not
59:59the same. So what happened
01:00:01between 1917 and 2018?
01:00:03The effort to put fraud in the
01:00:05rearview mirror? Psychology,
01:00:06psychiatry and brain science through
01:00:08the middle baby out with the bathwater.
01:00:10Until we accept that emotions are
01:00:12first and foremost mental states,
01:00:13efforts to treat mental
01:00:15disorders will languish.
01:00:16Patients, therapists,
01:00:17pharmaceutical companies,
01:00:18and researchers will all
01:00:20continue to be disappointed.
01:00:21So some of this is from anxious
01:00:23and the deep history of ourselves.
01:00:25And I have a bunch of fear
01:00:27rants that you can look up,
01:00:29and a bunch of clinical rants and
01:00:32some consciousness partition rents
01:00:33I don't have time to talk about.
01:00:35Thank you very much.
01:00:43Thank you Doctor Lulu for an amazing talk.
01:00:46I'm really blown away by by the
01:00:49breath of your work we're at.
01:00:50We're out of time now.
01:00:51If people would like to stay for questions,
01:00:54you can. If you need to go,
01:00:56please feel free to go.
01:00:56I apologize for using all the time.
01:01:00Thank you. Any questions?
01:01:03Come on, you got some Georgia.
01:01:07I guess I would think
01:01:08there are some thanks.
01:01:11I I would say there's some anyway
01:01:14that would emphasize interoception
01:01:15more than you appear to.
01:01:18And I just wonder what you
01:01:19would say to them or what
01:01:21your thoughts are about that.
01:01:23You know, I said the body
01:01:25responses are very important,
01:01:27but I don't I think that until those
01:01:30responses are cognitively interpreted.
01:01:32They're not giving you an experience,
01:01:35but the experience requires the
01:01:37interpretation of signals whether
01:01:38they're external signals or
01:01:40internal signals and that's what
01:01:41the these cognitive networks are
01:01:43important for that you know you
01:01:45and intraception is going to come
01:01:47into those come into the amygdala,
01:01:49hypothalamus,
01:01:50their aqueductal Gray and then they
01:01:51will go into the medial prefrontal
01:01:53areas that I was just talking about.
01:01:55So those medial prefrontal areas are
01:01:58providing kind of and I didn't have
01:02:00time to go into the last part which was.
01:02:02The partition of consciousness
01:02:04into three kinds of states that
01:02:06entail traveling talks about.
01:02:08One is autonoetic consciousness,
01:02:10which is reflective self-awareness.
01:02:12Basically it's based on episodic memory of
01:02:16who you are and what you know about yourself.
01:02:18No edit consciousness,
01:02:19which is based on semantic memory and the
01:02:22conceptual knowledge and semantic knowledge,
01:02:24and then a noetic consciousness,
01:02:26which is more of a kind of William
01:02:29James Fringe state that is simply there.
01:02:32You know,
01:02:33you know your body states are yours without
01:02:36having to affirm that they're your,
01:02:38that your mental state to yours
01:02:39without having their permit.
01:02:40But there are some people who have
01:02:42brain damage that lose the ability to
01:02:45know their mental states of theirs or
01:02:47to know their body states of theirs.
01:02:49And that's when it becomes apparent
01:02:50that we always know that our you know,
01:02:53unless your brain is is damaged
01:02:55in this way you know that your
01:02:57mental states are yours.
01:02:58So the idea is that when
01:03:01you have some kind of.
01:03:03Violation of that normality,
01:03:05what William James called the
01:03:07rightness of mental states.
01:03:09Then that's when you have to go
01:03:11into the more cognitive levels of
01:03:13consciousness to interpret them.
01:03:16But otherwise you're interoception
01:03:17is going to be one of those kinds of
01:03:21analytic States and medial prefrontal
01:03:23cortex and unless it becomes.
01:03:25For the sake of you know,
01:03:26if you have an intense body state,
01:03:29then it's not going to stay in the
01:03:32normal level of analytic consciousness.
01:03:33It's going to rise to have the
01:03:36semantic interpretation or even
01:03:38autonoetic interpretation of being
01:03:40something that you are personally
01:03:42involved with and conscious of.
01:03:44That's my two cents.
01:03:47Any more questions?
01:03:50Heartland.
01:03:56That was awesome and I turned around
01:03:58so happy to see two of my postdocs in
01:04:00the back because I always talk to them
01:04:02about how I think theory is so important.
01:04:04It's really fun to see the way you
01:04:06have evolved your own theories over
01:04:08time as and it's a mechanism to
01:04:09drive I think one's own work forward
01:04:11and a whole field forward.
01:04:13So thank you for that and I guess
01:04:14my question is you observe verbal.
01:04:16You said two things that struck me.
01:04:18One you tripped consciousness is is
01:04:20contingent upon brain mechanisms
01:04:21like everything else.
01:04:23Two you said that verbal report.
01:04:25Is a you
01:04:26know, is the the the best maybe way
01:04:29we can measure consciousness but.
01:04:31Would you think that there could be
01:04:33other biological things that we can
01:04:35measure that should be as we don't
01:04:36know yet but should be as indicative
01:04:38of consciousness and maybe better than
01:04:40verbal report. So there going to be lots
01:04:43of correlates, but the question is.
01:04:45How do we separate correlates from causes?
01:04:48You know and. That's the problem and I don't,
01:04:53I, I really don't know how we get past
01:04:55that because I think we can, you know,
01:04:58as a scientist, I'm more concerned with.
01:05:01What we can learn using verbal report then?
01:05:04As opposed to what?
01:05:06We can't learn from them.
01:05:07That makes any sense because I think.
01:05:11You know, with better understanding of
01:05:13neuroanatomy, we can make progress.
01:05:17Beyond where we stand right now,
01:05:19we need to build.
01:05:20The understanding of the brain and but
01:05:23not over interpret the brain because we
01:05:25need to have it the interpretations we
01:05:28develop have to go hand in hand right.
01:05:30We've got to understand something
01:05:31about the brain but we can't let
01:05:33the brain tell us what is conscious
01:05:35and that is not we verbal report
01:05:37is so good for that but again it's
01:05:40limited but we can make progress on
01:05:42that area now from the point of view
01:05:44of the clinician you know So what
01:05:46do we do well I think they're.
01:05:49You know, obviously you can't simply
01:05:51trust what the person says, right? But.
01:05:56If the person, if you can tell if
01:05:59the person is suffering and the
01:06:01behavioral treatments are the you know.
01:06:05Pharmaceutical treatments.
01:06:06How are you treating the
01:06:08person if they're not working?
01:06:09The person is still suffering, right?
01:06:11And maybe the reason they're still
01:06:13suffering is because even if they
01:06:15aren't telling you what's wrong,
01:06:16they're suffering mentally in a way that.
01:06:21Is more causal to their.
01:06:23What's their overall experience and
01:06:25what they're able to talk about?
01:06:27Because, you know, again,
01:06:29the preconscious cognitive states don't
01:06:31all come to conscious and to consciousness.
01:06:34So when I'm talking about consciousness,
01:06:37I'm including all that pre conscious stuff as
01:06:40part of the emotion part of the experience.
01:06:43And it can't all come out.
01:06:44Some of the will come out and
01:06:47unconscious or conscious,
01:06:48willful report.
01:06:49But some of it is stuck in there and
01:06:52you have to pull it out in other ways.
01:06:54So the science and the clinic
01:06:57don't always kind of you know
01:07:00go hand in hand completely,
01:07:02but I think they're they're probably some
01:07:05things that are valuable what I'm trying
01:07:07to say that could be helpful clinically.
01:07:10For example, like,
01:07:12take the whole psychedelic revolution.
01:07:15Maybe what's going on there
01:07:18is some borrowing from Kalina
01:07:21Christoff work on all this?
01:07:24Is the that the psychedelics are.
01:07:30Allowing you to have a a new higher
01:07:33order experience about who you
01:07:35are and what's going on, right?
01:07:37Because it's it's breaking down
01:07:39the rigid thought processes, right,
01:07:42and allowing novel thought process.
01:07:46And also, you know, mindfulness of
01:07:48course is about higher order States and
01:07:50the experiences that you have, right,
01:07:52and shutting down certain kinds of things.
01:07:55So I think that the. That we have.
01:08:01We need a broader perspective on.
01:08:03I can't explain how all these things work,
01:08:06obviously, but I think that the
01:08:08fact that the field is moving
01:08:10in this direction seems to be.
01:08:12Opening new avenues for
01:08:14thinking about this thing.
01:08:18I have a question,
01:08:19see if I can get this right.
01:08:20So as psychologists,
01:08:23psychiatrists we use questionnaires
01:08:26and if you think about it,
01:08:27each person interprets a
01:08:29liquor scale differently.
01:08:30They use their own semantic
01:08:32network to interpret item and then
01:08:35they fill out different items,
01:08:36they endorse different items.
01:08:38We sum those up,
01:08:39we have a number and we use that
01:08:42number to correlate with things and
01:08:43we usually do it after the fact.
01:08:46And some people use exemplar,
01:08:47they want to report my kids afraid of dogs,
01:08:49they think of an example, right.
01:08:50Something might just out in general,
01:08:52right.
01:08:52So all these things go into that
01:08:54subjective report and I worry that
01:08:56all we have known studies this right.
01:08:59And I just would like to hear your
01:09:00thoughts on it, I guess.
01:09:02I don't, I think that you know,
01:09:05you bring up an interesting thing
01:09:07which is the the use of metrics
01:09:10and I think that that's where.
01:09:14You know, obviously to.
01:09:17Be reimbursed for sessions and so forth.
01:09:21The patient has to be evaluated
01:09:23in in some metric way defined by
01:09:25the insurance companies, right?
01:09:27And because they want objective measurements.
01:09:31So. I think that we.
01:09:36That's part of where what I've met.
01:09:38But the middle has gone out of mental
01:09:40disorders because it's so much is
01:09:42based on the objective response.
01:09:44Now you know,
01:09:45I don't know enough about what
01:09:47people that what clinicians do
01:09:49with these Likert scales to really
01:09:51comment too much but So what
01:09:53what's the consequence of you're
01:09:54saying no consequence just done?
01:09:58There's a lot of consequences
01:09:59misinterpretation.
01:10:00So remember back having a client
01:10:02that came into clinic and the mom
01:10:04was saying ohh she's really anxious.
01:10:05You're anxious. And then we got
01:10:07into it. She yeah she she
01:10:09hits her brother and she you know and it was
01:10:11it was something it was driven by emotion
01:10:13and neighborhood reactive to anxiety.
01:10:15But it but it looks very different but
01:10:16the way she was using that language.
01:10:18There's that. Then there's. In our I just.
01:10:22I guess what I'm thinking is that the
01:10:24essence of a person's experience is is lost.
01:10:26But and and in all the ways that I described
01:10:29and I'm wondering if that short circuits
01:10:31are models, so I mean they.
01:10:34What I've been trying to say is that
01:10:37the experience is very complicated and
01:10:39that like sums a lot of information.
01:10:41So yeah, I think it's consistent
01:10:43with what you're saying.
01:10:43Can't partition it into little
01:10:45elements that that that are
01:10:47greater than the whole is greater
01:10:48than the sum of the parts. And
01:10:51I mean, I could vision we do.
01:10:53We see when when you assess a
01:10:54child from the parents perspective
01:10:55and the kids perspective,
01:10:56they have reports on different environments.
01:10:58Those don't correspond.
01:10:59But other examples could be would
01:11:00be good to know when someone filling
01:11:02out that questionnaire what what
01:11:03their semantic network looks like
01:11:05for the words that you've asked
01:11:06them about. And that may tell you
01:11:08something different about what those
01:11:10numbers mean when you use them to predict.
01:11:16George.
01:11:21I wonder if you. Ever
01:11:24had occasion sit down with Aaron
01:11:25Beck and had a conversation with him
01:11:28and and and the question is what you
01:11:31might bring from your research in
01:11:33terms of how you what suggestions
01:11:36you might have for CBT. In general,
01:11:38so I'm I collaborated quite a bit
01:11:42recently with Stefan Hoffman,
01:11:44who was very close to Beth.
01:11:46And we did have a meeting with
01:11:48him together a few years ago,
01:11:50but it was, you know, he was pretty.
01:11:52Getting on in age,
01:11:54so to speak and so we didn't get,
01:11:56I mean he was still relatively sharp,
01:11:58but we didn't get into a lot
01:11:59of the the details like.
01:12:01You know, in this paper,
01:12:02putting the middle back in the
01:12:04middle of this order stuff on has
01:12:06added some important ideas about.
01:12:10Early cognitive.
01:12:12Therapy, cognitive behavioral therapy
01:12:15was much more mental than contemporary
01:12:19cognitive behavioral therapy,
01:12:21again because of the kind of
01:12:23the objectifying of the things.
01:12:26That's about as far as I can say that the.
01:12:29You know, I think every course,
01:12:31every therapist wants their
01:12:32patient to feel better, right?
01:12:34To be better. But there's so many.
01:12:38As again, talking totally from the outside,
01:12:40there's so many.
01:12:43Things that are dictated about how they
01:12:46report and summarize what the what's
01:12:49going on with the patient that I think.
01:12:52It's it's hard for the memo to have
01:12:55the role that I think it should.
01:12:57Again, I'm not a therapist,
01:12:58so you're looking skeptical.
01:13:03But please tell. I mean I
01:13:04want to learn so tell me.
01:13:12Well, it's a quarter after.
01:13:14I want to thank you all for
01:13:14coming and and and Doctor Leduc.