The Jordan B. Peterson Podcast - 296. Neuroscience Meets Psychology ｜ Dr. Andrew Huberman

00:00:00.960 Hey everyone, real quick before you skip, I want to talk to you about something serious and important.

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00:00:57.420 Hello everyone. I'm pleased today to have with me Dr. Andrew D. Huberman.

00:01:14.040 He's a neuroscientist and tenured associate professor in the Department of Neurobiology at the Stanford University School of Medicine.

00:01:21.600 Dr. Huberman and his lab have made contributions to the brain development, brain plasticity, and neural regeneration and repair fields.

00:01:30.360 His work and his lab's work focuses on the visual system, elucidating the nature of neural mechanisms controlling light-mediated activation of the circadian and autonomic arousal centers in the brain,

00:01:42.920 and mediating conscious vision, and mediating conscious vision or sight.

00:01:46.940 His lab investigates how the brain works, how it changes through experience, it's a field known as plasticity, and how it repairs itself.

00:01:55.560 He and his colleagues have worked to discover strategies for halting and reversing vision loss in blinding diseases,

00:02:02.780 and understanding how visual perceptions and autonomic arousal states are integrated to impact behavioral responses.

00:02:10.780 His lab employs a large range of state-of-the-art investigative tools, virtual reality, gene therapy, anatomy, electrophysiology, and imaging and behavioral analysis.

00:02:22.200 In January 2021, Dr. Huberman launched the Huberman Lab podcast concentrating on neuroscience and other scientific topics.

00:02:30.320 It's done phenomenally well for a detailed scientific podcast, attracting 1.5 million subscribers.

00:02:38.500 It's very good to see you today, Dr. Huberman, and thank you for agreeing to talk with me.

00:02:43.280 Delighted to be here.

00:02:44.660 Your first book, 12 Rules for Life, sits prominently on our bookshelf in our living room,

00:02:49.660 and we've all read it and learned a tremendous amount from you over the years,

00:02:54.600 and certainly feel a kinship because of the shared relationship between university professorship and public education as well.

00:03:03.200 Right, right, right. Yeah, well, we've got lots in common.

00:03:05.640 I'm particularly interested in the neurological work that you've done on both anxiety and exploration,

00:03:11.440 although there's plenty of topics to talk about today and plenty of overlapping interests.

00:03:16.080 But it's been a while since I've reviewed the neuroscience literature pertaining to both anxiety and exploration,

00:03:22.980 and so maybe we could start by you laying out what you've discovered and how you're thinking about what you think anxiety signifies,

00:03:32.000 how it's related to exploratory behavior, which I think you described as something approximating courageous approach,

00:03:38.180 although you were talking about mice in that particular paper, and what you're thinking about with regards to the neural basis of these different behavioral responses, behavioral and emotional responses.

00:03:51.620 Sure, I'd be happy to.

00:03:52.720 And I should mention that these days my laboratory mainly focuses on humans.

00:03:55.800 We still do some mouse work, but in partnership with people in psychiatry, we're doing essentially equivalent experiments in humans,

00:04:03.380 so I'd be happy to elaborate there.

00:04:04.780 You know, many people perhaps, but not everyone, have heard of the autonomic nervous system, which simply means automatic.

00:04:11.980 It's a bit of a misnomer because without going too much into the history of that,

00:04:16.160 if you look back to the origins of medicine in the time of Galen and so forth,

00:04:20.840 when they were first, you know, dissecting cadavers and whatnot,

00:04:24.220 there was this idea of a nervous system or a portion of the nervous system eventually came to be that could control so-called vegetative functions,

00:04:32.360 meaning the rate of digestion and the really what neuroscientists typically think of as boring stuff.

00:04:38.600 But it's anything but boring.

00:04:39.680 It's the stuff that keeps you from urinating while you're asleep, unless you're a very young child, right?

00:04:44.780 And it's the stuff that keeps your digestion going as you command your attention to other things.

00:04:50.560 The autonomic nervous...

00:04:51.340 It's all the things that are too complex for us to think through.

00:04:55.720 That's right.

00:04:56.580 And they are, as you point out, immensely complex.

00:04:59.320 And, you know, nowadays with all this interest in the gut microbiome and things of that sort,

00:05:03.080 I mean, these are tremendously complicated operations that are happening generally below our conscious awareness

00:05:10.020 and that are indeed vegetative.

00:05:12.520 They can be controlled by emotion.

00:05:14.000 You know, we were all familiar with the idea that when we are emotionally distraught,

00:05:18.280 that our digestion can be different or et cetera.

00:05:20.920 But typically we can't control, for instance, in a conscious way, the rate of our digestion

00:05:25.600 or the speed of our heartbeat in any kind of direct way.

00:05:28.900 We can have a particular pattern of thought to control those.

00:05:31.620 But in general, those functions were thought to be vegetative and outside of our conscious control.

00:05:37.760 And the name autonomic nervous system sort of swallowed and overtook the vegetative part.

00:05:42.920 So it includes that, but also three main aspects of body to brain signaling.

00:05:48.180 And those three aspects are heart rate, could be quickening or slowing of heart rate.

00:05:54.040 We are and we can be very aware of that, some of us more than others.

00:05:58.540 Gut and especially the chemical composition and the extent to which our gut is empty or full.

00:06:06.400 So heart, stomach, and then rate of breathing and sort of depth of breathing,

00:06:11.580 meaning how much air we have available to us.

00:06:13.580 And I think the three main ways to think about the way that the brain and body communicate

00:06:18.600 is that it's either going to be mechanical or chemical.

00:06:22.580 Let's use the gut as an example.

00:06:24.300 Your stomach can feel acidic or it can feel nice and warm and fuzzy, whatever that is in a chemical sense.

00:06:30.860 Your heart rate can feel like it's going at a rate that's appropriate for your circumstances.

00:06:35.380 You know, if you're running, it could be quick.

00:06:36.820 And if you're sitting in a chair quietly at the doctor's office waiting to be called back there

00:06:40.960 and all of a sudden your heart starts racing, then you would think,

00:06:43.220 well, that's appropriate for that situation, but it's not uncomfortable, right?

00:06:46.280 It's out of sync with what you are doing, which is sitting.

00:06:48.880 So there's mechanical information and then there's chemical information.

00:06:52.720 And with respect to your lungs, you know, you can feel like you're out of air or you have plenty of air.

00:06:57.240 You can feel like your breathing is labored or it's easy or in the chemical sense that the air that you're breathing,

00:07:05.500 your lungs are burning or it feels easy to breathe.

00:07:07.940 So basically there's chemical and mechanical signaling from the body to the brain and the brain interprets all of that.

00:07:13.640 And we put all of that under the umbrella of the so-called autonomic nervous system.

00:07:18.220 And the autonomic nervous system can really be best thought of along a continuum.

00:07:22.100 And here I'll avoid complicated nomenclature, but I'll throw it out there for the aficionados.

00:07:26.200 Some people have probably heard of the parasympathetic and the sympathetic.

00:07:29.180 That naming is a little bit misleading.

00:07:31.480 Again, what we can really think about the autonomic nervous system as is a continuum

00:07:34.940 or more like a seesaw of at one end is alertness and at the other end is calmness, right?

00:07:41.760 That is translated to the so-called sympathetic and parasympathetic nervous system.

00:07:45.380 But I'll call it the alertness and calmness system just for sake of simplicity.

00:07:48.500 So it's sort of like a seesaw and it has different neural circuits.

00:07:51.720 And basically whether or not you feel very alert or panicked or alert but calm or a little bit of anxiety,

00:07:59.100 that's going to depend on the balance between this alertness system and the calmness system.

00:08:03.320 If you're having a full-blown panic attack, then the alertness system is, you know,

00:08:06.880 it's as if the seesaw is tilted all that way.

00:08:09.380 If you have, if you're deeply asleep, well, then the calmness system is really tilted down.

00:08:14.620 You could say that's portion of the seesaw.

00:08:16.100 This is all kind of obvious and dates back, you know, 100 years or so,

00:08:20.060 which isn't that long in the history of science, but we've known this sort of thing for a while.

00:08:24.060 Okay.

00:08:24.660 What's interesting and I think more relevant nowadays is to think about one's own interpretation of those

00:08:30.280 signals and how that relates to anxiety and, as you pointed out, exploration,

00:08:33.620 and then to think about where the nodes of control are.

00:08:37.120 In this seesaw model that I'm putting forward, the seesaw has to include what I would call a hinge,

00:08:44.780 a location in the middle in which you can voluntarily adjust the seesaw to either be

00:08:51.480 more tilted toward alert or more tilted toward a sleep.

00:08:55.460 And for many people, they find that their overall level of autonomic arousal is either inappropriate

00:09:03.480 or inadequate for the demands of their life.

00:09:06.640 Inappropriate meaning their heart is racing.

00:09:08.720 They feel more jittery, more as if movement would be the default and worry would be the default and

00:09:15.220 anticipation is the default than is appropriate for their circumstances.

00:09:19.560 Waking up in the morning and feeling stressed, for instance, immediately without any immediate

00:09:24.020 cause or maybe stress about real life events.

00:09:26.420 For other people, they feel more exhausted than they would like.

00:09:30.600 They're having a hard time leaning into the pressures of daily life.

00:09:33.360 Both of those, even though they have sort of polarized phenotypes, they look very different.

00:09:38.160 In one case, over-energized.

00:09:41.180 In one case, under-energized.

00:09:42.760 Both originate within the autonomic nervous system.

00:09:45.040 And we can reliably say from work done in animals and humans that that is not the consequence

00:09:49.940 of the alertness system or the calmness system being disrupted, but rather that that hinge in the

00:09:56.800 middle is dysregulated.

00:09:58.560 And we now know what that hinge is.

00:10:00.360 And this is based on work done by colleagues of mine at Stanford, in particular, a guy named

00:10:04.220 David Spiegel, who's our associate chair of psychiatry.

00:10:06.540 He's done a lot of work and it's actually, his father did a lot of work in the application

00:10:10.520 of clinical hypnosis, not stage hypnosis, but clinical hypnosis for the treatment of various

00:10:15.120 things.

00:10:15.500 But his work and some work in our laboratory now has shown that there's an area of the

00:10:20.420 brain that you're, you are familiar with Dr.

00:10:22.260 Peterson, which is the prefrontal cortex.

00:10:24.340 And in particular, the left dorsolateral prefrontal cortex, if you really want to get down in the

00:10:29.080 weeds about it, that has direct communication with two brain areas that are absolutely critical

00:10:34.960 for this issue of whether or not you feel right for your circumstances, whether or not

00:10:39.940 you translate that into a curiosity and exploration, or whether or not you translate it into this

00:10:45.000 thing that we call anxiety.

00:10:46.920 And those two areas are called the anterior cingulate cortex.

00:10:50.840 Again, I apologize for all the names, but the anterior cingulate cortex and the insula.

00:10:54.680 And I think if I were to make a prediction about what the buzzword is going to be in popular

00:10:59.140 neuroscience in the next five years, it's not the amygdala.

00:11:02.300 It's not the prefrontal cortex.

00:11:03.500 It's the insula.

00:11:04.540 The insula has a couple of different regions, but one of its primary regions, the front end,

00:11:09.120 the anterior insula is responsible for interpreting all those bodily signals.

00:11:14.760 It essentially is a funnel for all those signals about breath rate, heart rate, conditions

00:11:20.500 of the gut, whether or not your body feels ready to move or exhausted, et cetera.

00:11:25.760 And that all funnels into the insula.

00:11:27.660 And then also coming into the insula is information from classical areas like the amygdala, which

00:11:32.600 are involved in threat detection and fear, and also emotion and memory.

00:11:37.540 So the insula is really this incredible hub of information about somatic signals, about bodily

00:11:43.020 signals.

00:11:43.520 And then the prefrontal cortex, the dorsal lateral prefrontal cortex in particular, is

00:11:47.980 in communication with the insula and literally makes a difference.

00:11:51.560 So let me ask you about that.

00:11:53.360 So does that mean that the body, in some sense, is reporting to conscious awareness?

00:11:59.220 Now, it reports unconsciously in all sorts of ways, too.

00:12:01.720 So it might report to the hypothalamus, which is a very low-level brain control area, by the

00:12:06.280 way, for those of you who are listening.

00:12:07.800 It might report to the hypothalamus primarily unconsciously.

00:12:10.900 But do you think it's the insula that's reporting on the nature of bodily states to the prefrontal

00:12:17.780 cortex in a manner that allows us to be consciously aware of our body states?

00:12:21.840 That's exactly right.

00:12:22.340 Is that part of that integration system?

00:12:23.680 That's exactly right.

00:12:24.900 You're exactly right.

00:12:26.060 The insula sits as a different sort of station in that it's reporting to the conscious areas

00:12:32.360 of the brain, to the prefrontal cortex.

00:12:35.020 Right.

00:12:35.220 So we can take our own physiological state into account then when we're envisioning plants,

00:12:40.580 because part of what the dorsolateral prefrontal cortex does is allow us to envision different

00:12:45.680 possible futures.

00:12:46.800 And those are plans.

00:12:47.840 And you're not going to make a plan to run two or three blocks to get to the corner store

00:12:52.660 if you're so exhausted you can't get out of bed.

00:12:54.500 And you need a reporting mechanism that tells you what physical state you're in so that

00:12:58.680 you can predicate your plans on that.

00:13:00.140 You think the insula, at least in part, is responsible for formulating those representations

00:13:04.680 or for reporting those representations?

00:13:06.920 That is exactly right.

00:13:07.940 In fact, the animal data and the human data, both lesion data and reversible inactivation

00:13:13.880 data, support that in humans.

00:13:15.920 So you have that exactly right.

00:13:17.620 And as you mentioned, the prefrontal cortex, you know, it gets sort of thrown out there for

00:13:22.180 everything.

00:13:22.660 I think, you know, nowadays people have probably heard of the prefrontal cortex and people hear

00:13:25.780 about executive function, which of course is true.

00:13:28.280 But if we were to really dial back and say, what is the prefrontal cortex in the position

00:13:33.260 to do?

00:13:34.180 It's a flexible rule setting structure.

00:13:38.360 How do we know that?

00:13:39.420 I'm sure you are probably more familiar than I am with the classic Stroop task.

00:13:43.520 You know, you give somebody a bunch of cards with different words on them, and those words

00:13:48.180 are written in different colors.

00:13:50.340 And you tell the person, okay, just read the words to me.

00:13:54.500 Ignore the color that they're written in, just read them.

00:13:56.400 And so they're saying they're cat, dog, shelf, book, professor, student, et cetera.

00:14:01.220 Then you quickly change the rules and you say, you know what?

00:14:05.100 Just tell me the color that the words are written in, but ignore what the words say.

00:14:09.920 And people will do that, but there's a portion of time in which they slow down a bit.

00:14:15.200 It's actually hard because you've done a rule switch.

00:14:17.660 Much of life, as you know, and again, this is more your domain than mine, is about applying

00:14:22.840 different rules in different contexts.

00:14:24.660 Now, what we know is that the insula and the prefrontal cortex are both intimately involved

00:14:30.760 in this conversation that establishes which rules are appropriate for a given situation.

00:14:36.840 So for instance, if somebody were to say something that quote unquote triggers me, okay, I'll use

00:14:44.340 myself as the example, right?

00:14:45.960 Maybe somebody will tweet something and I'll think, oh, you know, and I immediately want

00:14:50.360 to respond in a way that I know I can kind of like flip them on their back immediately.

00:14:55.400 But then I think, ah, you know, maybe I want to refrain from that for a number of any number

00:14:59.180 of different rules or reasons, right?

00:15:01.180 Well, then I have, I'm starting to apply different rules.

00:15:04.440 I'm starting to think about the context that's outside of the autonomic response because in a

00:15:09.260 strict, very animalistic way, in other words, in the absence of an insula and a prefrontal

00:15:13.860 cortex conversation, really the only thing an animal or human needs to do is just respond

00:15:20.320 to their arousal in, you know, it's either, uh, you can either retreat, you can stay put

00:15:25.800 or you can fight, right?

00:15:27.400 That's really the only three, three major.

00:15:29.420 And those are very fast responses generally.

00:15:31.780 So, so, so, so let me ask you about the role of the prefrontal cortex in what you described

00:15:37.320 as rule of switching because I would, I would like to know what you think about whether or

00:15:43.120 not the prefrontal cortex is actually, let's say, switching rules or if it, if what it's

00:15:48.920 doing is switching context, sensitive behavioral patterns that when we talk about, we describe

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00:17:31.760 It is the critical question that you're asking.

00:17:39.240 The prefrontal cortex, in particular the left dorsolateral prefrontal cortex, is in an incredibly

00:17:45.000 unique position to not only establish different rules depending on context, and the way it

00:17:51.600 does that is by accessing memory.

00:17:53.260 So the hippocampus has access to prefrontal cortex and vice versa.

00:17:56.700 It's almost always a reciprocal conversation.

00:17:58.420 So it can pull memory thinking, oh, you know, the last time I responded like that didn't

00:18:02.380 get me the result I wanted, or the last time I responded in this other way, I got the result

00:18:07.580 I wanted.

00:18:08.320 Again, regardless of situation.

00:18:10.000 The other thing that the left dorsolateral prefrontal cortex is exquisitely positioned to

00:18:14.780 do, and this is beautiful work of a colleague of mine by the name of Nolan Williams, also

00:18:19.340 in psychiatry, is because of its connections to some structures that then feed into the

00:18:24.380 vagus nerve, it actually can slow the heart rate down.

00:18:28.780 So in other words, let's say someone says something and your immediate impulse is to

00:18:32.340 fight or to respond in a kind of knee-jerk way.

00:18:36.360 If you halt, right, I guess what the meditators and the mindfulness folks was called the gap,

00:18:41.400 or if you can access some memory and think, ah, and you might be thinking, you know, actually

00:18:45.540 there's a much better way to place the dart if I just kind of lean back a little bit,

00:18:49.060 or it could be, you know, silence might be the best response, right?

00:18:52.880 Or it could be that you're going to carefully access some data from your hippocampus to respond

00:18:57.880 in a way that is most effective.

00:19:00.300 For instance, here I'm talking about confrontation, but it could be any situation.

00:19:03.360 The left dorsolateral prefrontal cortex does two things.

00:19:07.100 As it acquires a new rule set or starts to access information about a new or possible

00:19:13.060 rule set, it also sends a parallel signal to slow the heart down through the vagus nerve.

00:19:19.240 And that is, I think, one of the more important and fascinating discoveries in the last five

00:19:23.540 years.

00:19:23.780 Those aren't data from my laboratory.

00:19:25.660 I wish they were.

00:19:26.760 But it's very clear that when we start accessing alternate rule sets, there's a signal that

00:19:33.340 quiets the body in some way and position.

00:19:36.560 Is that partly how you calm yourself down?

00:19:38.680 That's right.

00:19:39.480 It is how you calm yourself down.

00:19:40.840 And again, you have the clinical background, not I.

00:19:44.020 But I'll confess, I've been in therapy enough to know that occasionally, you know, one feels

00:19:50.100 as if you're accessing some piece of information as the patient side.

00:19:53.220 I can only report from the patient side.

00:19:55.060 You know, accessing some what feels like important piece of information, you're pulling on a thread

00:19:59.500 of some sort.

00:20:00.620 But then the therapist will say something and it literally gives you that alternate view.

00:20:05.860 And this notion of looking at things through a different perspective, we often think about

00:20:09.780 that as a switch in our cognitive frame, in our thinking.

00:20:13.880 But also, we now know there's this parallel signal that's sent to the body in which in

00:20:18.420 order to access these alternate rule sets, new ways of looking at things, there's a calming

00:20:22.940 signal literally sent to the body as well.

00:20:25.380 And I find this conversation fascinating because normally we just think about anxiety and exploration

00:20:31.180 and rule setting and rule responses or responses to rules, et cetera, as a kind of the body

00:20:36.960 sends signals and the brain does all this, what neuroscientists have always talked about

00:20:40.480 as top-down processing, right?

00:20:42.260 Just sort of suppress the hypothalamus, control the limbic system.

00:20:45.800 Right.

00:20:45.860 And that's true to some extent, but there's also, it's clear there are signals being sent

00:20:50.160 to the body in parallel.

00:20:52.080 And rather than look at the signals...

00:20:53.940 It's more like conducting than suppressing.

00:20:56.040 Exactly.

00:20:56.640 Like conducting, like an orchestra, orchestrator conducts.

00:20:59.520 Exactly.

00:21:00.240 And there's a very interesting phenomenon that takes place in people that have chronic anxiety

00:21:04.800 or for people who essentially stop accessing alternate rules and responses to these signals.

00:21:12.240 And this is, I think, what is showing up in chronic anxiety, certainly in certain forms

00:21:16.660 of depression and when people enter states of rage and dysregulation, is that normally we

00:21:22.660 know based on neuroimaging that the prefrontal cortex is essentially leading the response of

00:21:29.940 this anterior cingulate cortex in the insula.

00:21:32.400 So information is coming up from the body into the insula and then being fed to the prefrontal

00:21:36.880 cortex.

00:21:37.360 But then the prefrontal cortex is actually in a position to lead responses.

00:21:41.000 And it essentially is acting like the coach of a team.

00:21:44.260 And the team is all these structures like the ACC and the anterior cingulate cortex and

00:21:48.000 the insula, the heart rate and so forth.

00:21:50.040 What happens in individuals who have chronic anxiety or damage to the prefrontal cortex or

00:21:55.620 dysregulation of these circuitries is that that order actually reverses.

00:22:01.660 The insula and ACC start leading and directing the response of the prefrontal cortex.

00:22:06.780 And I think, you know, we see this in, I'm sure you've seen this clinically in individuals.

00:22:11.400 And while this isn't necessarily a discussion about society at large, I mean, we see this

00:22:16.120 in dysregulated arguments and dysregulated combat where people is essentially losing

00:22:23.280 themselves and they default to one, what appears to be very primitive rule set.

00:22:28.080 And it may or may not be the appropriate one, but you and I, of course, have the good fortune

00:22:32.820 of knowing a number of people who've worked in special operations and things like that.

00:22:36.300 And you talk to any of those individuals and they know from experience and from training

00:22:40.920 that their ability to access multiple rule sets and options in the moments of extreme

00:22:48.520 autonomic arousal is actually where their power lies, right?

00:22:52.100 It's the, or a, or a combat fighter, or let's just take, or in debate, right?

00:22:56.580 Something that you're far more versed in than I am, right?

00:22:59.000 Although I guess every academic has to deal with a bit of that coming up, the thesis defense,

00:23:03.520 et cetera.

00:23:04.160 In a really good debate, you can't allow the autonomic response to overtake you or you lose

00:23:11.580 access to an enormous database that resides in your, one's hippocampus.

00:23:16.240 And you essentially, one then defaults to the bodily state, right?

00:23:20.640 And this is what we see when we see people become dysregulated in rage, et cetera.

00:23:24.540 So if we were to zoom out and then ask, you know, where is the line between exploration

00:23:29.680 and anxiety?

00:23:30.360 I think that we can check off a few boxes for sure.

00:23:33.260 First of all, that autonomic arousal, this, this tendency to be more alert or more in action

00:23:39.820 than in non-action is a very healthy response.

00:23:43.920 I mean, the moment adrenaline is released from the adrenals and, and as you know, there's a

00:23:49.020 parallel signal in the brain, you know, you get adrenaline released from the adrenals.

00:23:52.260 If you get in a cold shower or somebody says something triggering, or you are afraid of

00:23:56.560 heights or something, but the brain has its own kind of adrenaline system, which is this

00:24:00.740 structure in the back of the brain called locus coeruleus.

00:24:03.240 And it basically has a, it essentially sprinklers the entire brain with noradrenaline and adrenaline.

00:24:08.980 It's a very interesting system.

00:24:10.300 It lacks specificity.

00:24:11.960 It basically wakes up the whole brain.

00:24:13.640 If you were to, if I were to put a little, if I were to label the connections of the

00:24:17.980 locus coeruleus, it's basically connected to everything.

00:24:20.080 It just kind of sprinkles a caffeine-like substance on the entire brain, wakes you up.

00:24:24.880 The adrenals in the body wake up the body.

00:24:26.840 So two parallel systems wake us up.

00:24:29.160 Is that associated with the orienting reflex?

00:24:31.860 Yes.

00:24:32.160 If you orient, does the locus coeruleus wake up the brain?

00:24:34.920 Absolutely.

00:24:35.480 Yeah.

00:24:35.660 So it's a key component of the so-called reticular activating system.

00:24:39.760 Ticular activating system.

00:24:40.700 Yeah.

00:24:41.100 And incidentally, I should mention this because I was going to come to this later, but I think

00:24:47.320 it's relevant now.

00:24:48.340 If somebody has a lesion in their dorsolateral prefrontal cortex, or if you transiently inactivate

00:24:54.080 it with a technology, a non-invasive technology like transcranial magnetic stimulation, they

00:24:58.500 can now just put a magnet on outside the skull and quiet that area of the brain transiently.

00:25:02.880 In animals or humans, what you find is that that person or human becomes incredibly accurate

00:25:08.920 at any motor task.

00:25:11.300 So for instance, if I were to give you a shooter game where you're supposed to shoot targets

00:25:15.800 and you're shooting targets, you'll have some hits and some misses like anybody.

00:25:21.280 Um, if I inactivate your dorsolateral prefrontal cortex, your accuracy goes through the roof.

00:25:28.440 It's near 100%.

00:25:29.740 But the one thing you can't do is decide whether or not you're shooting an enemy or a, uh, or

00:25:36.640 a friend.

00:25:37.620 So you can no longer establish rules.

00:25:39.560 You just become very good at execution of the motor behavior.

00:25:43.160 Similarly in an animal or person without a dorsolateral prefrontal cortex.

00:25:46.780 You see a trade-off there, right?

00:25:48.300 Between, between specificity and, and flexibility.

00:25:51.640 That's right.

00:25:52.400 And so, and so we see this theme over and over again, where as a purely, you know, sensory

00:25:58.300 motor response machine, the prefrontal cortex isn't even necessary.

00:26:02.480 In fact, if you get rid of it entirely, people become like machines.

00:26:06.020 If I click over here, somebody has no prefrontal cortex.

00:26:08.280 Basically everything becomes a stimulus, a puppy.

00:26:11.280 Everything's a stimulus.

00:26:12.100 You know, I used to have a bulldog when he was a puppy, he had to worry about leaving

00:26:15.820 cords out and everything was, it went into his mouth by time he was, you know, a year

00:26:20.580 old in part, because he was a bulldog.

00:26:22.420 He just kind of lay there.

00:26:23.260 Like you could put a toy in front of him and he wasn't into playing and just leave it alone.

00:26:26.880 A baby, everything's a stimulus.

00:26:29.020 Many adults become infant like in their responses, right?

00:26:34.120 When anxiety is high.

00:26:36.700 In fact, I have a friend who's a psychologist.

00:26:38.360 Tell me if you agree with this statement or not, that anxiety makes children of us all.

00:26:42.100 I don't know if that's true or not, but it certainly has been my experience that when

00:26:46.700 feeling anxious, I don't struggle with chronic anxiety, but I certainly feel like, have felt

00:26:51.080 anxiety.

00:26:52.100 Well, it simplifies us.

00:26:53.580 I mean, all these underlying emotions and motivational states, these primordial instincts

00:26:58.620 are simplification mechanisms.

00:27:01.320 And so if we're unable to compute a complex and sophisticated pathway forward that takes

00:27:07.300 multiple variables into account simultaneously, we can't just do nothing.

00:27:11.960 We're going to default to a more primordial and direct state.

00:27:15.600 And then you might say the whole panoply of emotions and motivations lies there at the

00:27:20.720 weight for us to grip our behavior.

00:27:22.980 If we're, what would you say, if we're paralyzed by inability to choose between multiple options.

00:27:29.060 And so we do, to the degree that we're simplified by an emotion, then we're reduced to something

00:27:33.300 more approximating an infantile state.

00:27:35.760 If you watch two-year-olds, and two-year-olds are particularly interesting in this regard,

00:27:40.460 they basically just cycle through innate motivational states.

00:27:45.080 It makes them really interesting to be around, because when they're interested in something,

00:27:48.700 they're 100% interested in it.

00:27:50.960 And then when they're angry, they're 100% angry.

00:27:53.500 And if they're anxious, they're 100% anxious.

00:27:56.300 And they can, and tired, they just instantly fall into a coma.

00:27:59.900 And they just cycle through these with no overarching centralized integration.

00:28:04.460 And it's partly because they likely don't really manifest any integrating prefrontal cortical

00:28:15.260 capacity until they hit about three, where they can start to engage in joint play states

00:28:20.700 with other children, right?

00:28:22.300 And then they can exercise, then they can modulate their underlying emotions in accordance with

00:28:27.840 an abstract representation or goal, sometimes that's jointly shared.

00:28:31.580 That's part of developing sophistication.

00:28:33.280 It's also why the idea that identity is subjectively defined is absolutely preposterous.

00:28:37.800 It's like, it's subjectively defined for two-year-olds, but it's not subjectively defined

00:28:42.300 for anyone who's sophisticated enough to negotiate with someone else.

00:28:46.120 And so tell me about, tell me what you think about this.

00:28:49.160 My understanding of the prefrontal cortex is that over the course of evolutionary time,

00:28:54.500 it grew out of the frontal cortex and out of the motor cortex more specifically.

00:28:59.760 And so the best way to think about what the prefrontal cortex does in some sense is that

00:29:04.960 it generates potential abstract patterns of action.

00:29:09.520 It generates them in abstraction so that they can be assessed before they're implemented.

00:29:14.760 And so it's like it's generating potential future selves.

00:29:17.420 That's exactly right.

00:29:19.080 That's okay.

00:29:19.900 That's exactly right.

00:29:20.780 And I'm glad you stated it, not I, because you stated it far more clearly and succinctly

00:29:27.320 than I've heard it stated before.

00:29:29.780 It's as if it's running plays.

00:29:34.580 I'm using a sports analogy.

00:29:36.400 It's running plays and thinking about potential outcomes.

00:29:38.800 You know, I'm not a chess player, although, you know, Lex Friedman's podcast and Lex Friedman

00:29:43.920 are convincing me that perhaps I should learn because there's a lot of discussion about chess

00:29:47.640 nowadays.

00:29:48.220 And there's a lot of thinking, as I understand, about potential outcomes.

00:29:51.800 You know, how many moves can you anticipate if this, then that?

00:29:54.900 It's sort of if this, then that type of thinking.

00:29:57.720 And if you think about its connectivity, it's in a beautiful position based on its access to

00:30:02.600 priors through the hippocampus of memory.

00:30:05.120 It can take into account current state, bodily state.

00:30:08.880 It can access information, for instance, about do I have the energy?

00:30:11.580 Do I have the resources to undergo a particular pattern of response?

00:30:16.740 And that's through the insula and the ACC.

00:30:19.760 And then the dorsolateral prefrontal cortex, in this way of also being able to control the

00:30:25.100 body, of being able to calm the body, this is a very unique pathway because typically we

00:30:30.980 think of the heart rate as going up if we're excited or scared and heart rate going

00:30:34.780 down if we're calm.

00:30:36.140 But really, the default of the neural inputs to the heart and to the breathing systems,

00:30:41.240 et cetera, are to be very activated.

00:30:43.740 And then the brain provides a suppressive or kind of a breaking on that entire system.

00:30:48.780 The vagus nerve.

00:30:50.040 Right.

00:30:50.280 So it's a default on system.

00:30:51.880 It's a default on system.

00:30:53.240 And the vagus nerve, which, of course, is a massive nerve pathway.

00:30:56.080 Again, it makes it sound like one little nerve, but it's this huge superhighway of connections

00:30:59.560 between brain and body is classified in medical school as a parasympathetic pathway, meaning

00:31:06.020 of the calming system, kind of generically speaking.

00:31:09.800 And indeed it is.

00:31:10.780 And so the prefrontal cortex, we can think of as, remember in the seesaw analogy, the

00:31:17.600 hinge.

00:31:18.460 The prefrontal cortex is more or less like the screwdriver that tightens that hinge, essentially

00:31:23.920 makes sure that the seesaw stays at a level, at a tilt that's appropriate for whatever

00:31:29.980 it is that you happen to be doing.

00:31:32.020 Okay.

00:31:32.220 Now, I presume it does that.

00:31:34.460 So imagine, so to continue the evolutionary analog, so an animal that doesn't have a lot

00:31:41.560 of behavioral flexibility, generally its reproduction strategy is multiple copies of itself, maybe

00:31:46.820 hundreds, maybe thousands.

00:31:48.220 And the reason for that is all the variability in the animal's behavior is genetically coded.

00:31:52.480 And so for it to adapt to the transforming horizon of the future, it has to produce multiple

00:31:58.200 variants of itself, most of which die.

00:32:01.020 With mosquitoes, for example, they produce thousands of eggs.

00:32:04.140 And if they all lived, we'd be knee-deep in mosquitoes in like 10 years.

00:32:07.300 But they almost all of them die because they're not matched to the transformation that's coming

00:32:12.160 down the pipeline.

00:32:13.280 But with human beings, what we seem to have done is evolved a mechanism for manufacturing

00:32:19.540 artificial selves in this game-like manner.

00:32:23.560 And so we can put forward optional selves in abstraction and then kill them off when 0.82

00:32:30.360 they're not necessary without us dying.

00:32:32.420 And so the famous quote, I think it was Alfred North Whitehead, was that the purpose of thought

00:32:36.160 was to let our thoughts die instead of us.

00:32:39.220 I love that.

00:32:39.880 And it really makes us unique.

00:32:41.280 Yeah, it's great.

00:32:41.960 It's absolutely great.

00:32:42.880 And so then it seems to me too, you tell me what you think about this, is that the abstracted

00:32:51.200 artificial selves, avatars in some sense, that the prefrontal cortex generates, or that

00:32:58.420 it allows these underlying motivational and emotional systems to generate, because they

00:33:02.760 can generate simple avatars by themselves.

00:33:05.260 I think when we describe those, we're describing, we're telling stories.

00:33:10.260 When we describe one of these alternative modes of action, that's precisely, the verbal

00:33:15.680 description of that is a story.

00:33:17.200 That's right.

00:33:18.000 And you make a very important point, which is that the prefrontal cortex is a rule-changing,

00:33:24.200 alternate self-accessing machine that can also calm the body.

00:33:29.440 And here I'm making up a just-so story, because as I always say, I wasn't consulted at the

00:33:34.140 design phase, and so I don't know why it's set up this way.

00:33:37.000 I just know that it is set up this way.

00:33:40.380 One reason to suppress the somatic response, the bodily response, is that tends to be a

00:33:47.320 unitary interpretation, meaning at this moment, I feel alert but calm, so I feel good.

00:33:53.600 But I'm guessing there's a lot of signals coming from the body, and in fact, there are

00:33:57.740 to my brain, but I tend to just say, I feel pretty good.

00:34:00.420 In fact, I'm very delighted to be here, so I feel good.

00:34:02.220 Or if I'm very tired, I feel tired.

00:34:04.220 Those tend to be very kind of binned responses, and they're fairly generic.

00:34:09.900 Whereas your description of what the prefrontal cortex does, which is an accurate one, I should

00:34:14.180 say, of imagining different selves and different outcomes almost requires that we suppress how

00:34:20.040 we feel in our body in the moment.

00:34:23.020 You know, I guess we can look to some of our podcasting colleagues, like the Jocko Willinks 0.99

00:34:28.120 or the David Goggins, you know, who are either forcing themselves or are somehow up at 4.30

00:34:34.880 in the morning and pushing through that, what I call limbic friction.

00:34:38.180 You know, the limbic system is saying, I'm tired or I'm anxious and going against that.

00:34:42.800 So there's literally a required suppression of the bodily response in order to imagine how

00:34:49.260 we would feel when we complete this or how terrible we would feel.

00:34:52.400 How much of that, how much of that, so let's parse that into two parts, because you could

00:34:57.640 imagine there's an inhibitory component where you're directly in competition with an underlying

00:35:02.200 urge.

00:35:02.760 So the top-down story is, so for example, if you're responding to something in an irritable

00:35:08.440 way that's being directed to you on Twitter, there's going to be a limbic rage response that's

00:35:13.680 associated with that, which you can then suppress.

00:35:15.880 But then the question there that's quite complex, I would say, is something like, to what degree

00:35:21.500 do you think you're directly suppressing that with the prefrontal cortex, and to what degree

00:35:25.520 do you think you're spinning up an alternative self that, if embodied, wouldn't require that

00:35:33.060 physiological response?

00:35:34.420 And so you're switching to a new identity in which that limbic response is no longer germane.

00:35:42.200 And so the reason that it disappears is not because you directly suppress it in an inhibitory

00:35:46.800 manner, but because you replace what's necessary physiologically, given your new understanding

00:35:52.240 of the territory that you inhabit.

00:35:54.240 I think it's some of both, but I've never been able to really, like, wrestle that through.

00:35:58.560 Yeah, so I think what you're getting to is, what we know is that the prefrontal cortex and

00:36:03.500 its associated networks contain a near-infinite, if not infinite, set of possibilities, right?

00:36:09.680 I mean, of course, it's bottlenecked by experience, and it's bottlenecked by one's imagination.

00:36:17.640 But, you know, the number of different possible cells that one could imagine is near-infinite

00:36:21.700 if one were to spend time on it.

00:36:23.500 Whereas the number of different bodily states that one can have are actually very finite.

00:36:30.620 And if you think about the autonomic nervous system, and in my laboratory, we've studied

00:36:35.300 this typically in the context of fear and confrontation, that the simplest way to put this in a kind of

00:36:41.780 pop neuroscience way would be to say, you know, we can either be back on our heels, meaning

00:36:47.860 retreating, or we can be flat-footed, sort of calm in our stance, or we can be forward center

00:36:53.020 of mass.

00:36:53.620 We can be in sort of pursuit and or competition.

00:36:57.240 There really aren't other motor responses for an animal, including humans, right?

00:37:02.460 You can either stay put, back up, or go forward.

00:37:06.120 You know, and this is...

00:37:06.820 Yeah, well, it's useful for people to know that that's the basic platform upon which emotions

00:37:11.440 are erected, too, is that emotions are like signals of those action tendencies.

00:37:16.560 And they are very simple.

00:37:17.720 It's back up, get away, stop, or move forward.

00:37:21.760 And so generally, we associate positive emotion with forward movement.

00:37:25.480 And that would be positive emotion that's dopaminergically mediated, fundamentally.

00:37:29.040 And then the halting would be, well, it can be calmness because there's nothing to do,

00:37:33.640 but it can also be the paralysis that fear induces.

00:37:36.900 And then panic and retreat are more, they're sort of on the border between anxiety and pain,

00:37:42.640 I suppose, pain responses.

00:37:44.700 Yeah, exactly right.

00:37:45.620 It's complicated in...

00:37:46.980 Yeah.

00:37:47.480 So these three major categories, I think, encompass most, if not all, of the possible responses,

00:37:52.700 as you said, and probably form the base set for all emotions.

00:37:56.200 I mean, my laboratory studied this mainly in the context of fear and confrontation.

00:38:00.060 And one of the reasons we started to explore this was the following.

00:38:03.060 You know, we've all heard of fight or flight or rest and digest, right?

00:38:07.140 Those correspond to the alertness system and the calmness system of the autonomic nervous

00:38:11.500 system in their kind of extreme forms.

00:38:13.140 But what we observed in animals and then now in human studies, we published about a year ago,

00:38:18.320 is that when people are confronted with an anxiety-provoking scenario, in our case, we do this

00:38:24.220 with virtual reality because we need to do it in the laboratory, we find that we find

00:38:27.960 their pain point, essentially.

00:38:29.240 And by pain point, I don't mean extreme fear.

00:38:30.960 I mean, the thing that can raise their autonomic arousal, that has them in a mode of considering

00:38:35.420 different options and trying to figure out what is strategic and what they're capable of

00:38:39.100 in that moment.

00:38:39.920 Could be heights, could be confrontation with a predator, animal, it varies by person to

00:38:45.200 people, but everyone has their pain point.

00:38:46.900 Even Navy SEALs that we brought to the laboratory or other people from the special operations

00:38:52.340 community, they all, each and everyone has their pain point.

00:38:55.680 What they do in response to that pain point is really what's interesting.

00:38:58.760 And what we found was that the pause or freeze response certainly was associated with autonomic

00:39:05.720 arousal, with stress and anxiety.

00:39:07.480 We measure this in the brain and body.

00:39:10.440 But it was the lowest anxiety response.

00:39:13.540 People always think of panic, you know, just being paralyzed in panic.

00:39:16.020 That's actually the lowest anxiety response.

00:39:18.460 Retreat was the next level up in terms of levels of heart rate change and levels of change

00:39:24.740 within the insula of all places.

00:39:26.380 We actually recorded from human insula through a partnership with neurosurgeons.

00:39:31.060 And then we found that there were a subset of individuals and animals in the parallel

00:39:34.700 animal work that would confront a fear, not necessarily reflexively, but after some consideration, they

00:39:41.760 would lean into the challenge, essentially confront the thing that was making them feel

00:39:45.380 anxious.

00:39:45.740 And it turned out that that response, surprisingly, was associated with the highest levels of

00:39:51.440 autonomic arousal.

00:39:53.120 And this gave...

00:39:53.620 Right.

00:39:53.840 So, but that would be heart rate activation particularly?

00:39:57.260 Heart rate activation and a change in what it's called the so-called gamma wave activity

00:40:03.600 in the insula.

00:40:04.680 We had electrodes in the insula.

00:40:06.500 And what we found was that people who were willing to lean into that challenge, the insula 0.68

00:40:12.540 took on essentially a change in its activity patterns, this gamma pattern.

00:40:17.420 The heart rate increased, breathing increased, sweating increased.

00:40:21.500 So these are all the marks of an anxiety attack.

00:40:24.100 But here, if you were to just look at the behavior of the person or the animal, what you'd

00:40:28.260 find is that they were marching forward toward their fear.

00:40:30.960 This is the...

00:40:31.860 You know, and so then...

00:40:32.820 That's voluntary exploration.

00:40:34.500 Right.

00:40:34.980 So now you did an animal study with mice where you showed, if I remember correctly, that the

00:40:40.100 mice that were showing tail flicking, which was a prodroma to that exploratory activity,

00:40:44.560 showed a particular form of brain activity that if you replicated with stimulation was more

00:40:50.320 potently reinforcing than sexual stimulation.

00:40:52.940 Right.

00:40:53.400 So here's where the surprise came, the additional surprise came in.

00:40:58.160 We thought, okay, wow, well, there are animals, these mice will tail flick in response to a

00:41:02.640 threat, which is essentially saying, come on, let's go, let's fight.

00:41:05.800 Whereas other animals would retreat.

00:41:07.860 And that tail flicking paralleled in the human studies with people being confronted with it.

00:41:12.620 For somebody who's scared of heights to go through a virtual reality scenario of being

00:41:16.500 up on a high beam between buildings might not sound like a big deal to the average video

00:41:20.240 gamer or to you and me, but is an absolutely terrifying experience for those people.

00:41:25.300 But a subset of them will just march out onto that platform or even explore jumping off the

00:41:30.560 platform with the understanding that it's virtual and get very scared, but they will do it.

00:41:35.660 And they also show these changes in insulin activity and changes in heart rate and breathing.

00:41:40.300 What was interesting to us was the mouse data told us that if you stimulate the brain area

00:41:45.460 that was associated with all of this, it's an area of the midline thalamus.

00:41:49.480 I don't want to get down into details of structures too much, but it was a very mysterious area,

00:41:53.740 not been explored much before, had this incredible name of nucleus reunions.

00:41:58.100 Why?

00:41:58.340 I don't know.

00:41:58.940 The neuroanatomists name these things peculiar ways, as you know.

00:42:01.820 But if we were to stimulate that brain area in mice, we could convert a terrified, non-confrontational

00:42:07.320 mouse into a mouse that was willing to confront its fears in a healthy and adaptive way.

00:42:11.880 It wasn't being foolishly running into the jaws of a predator.

00:42:15.160 It was being very strategic in its confrontation.

00:42:17.260 The interesting thing was if we introduced no fear stimulus, no heights, no predator,

00:42:24.780 no nothing, and we just tickle this brain area, what we found is that animals and humans

00:42:30.720 love that feeling.

00:42:33.160 In fact, they will work for that feeling more than they will work for other stimulation.

00:42:37.100 And in how do, okay, so a bunch, I've got a bunch of questions about that.

00:42:41.560 So the first is, how do you think that's related to hypothalamic dopaminergic release in exploratory

00:42:48.220 states and the psychomotor stimulative effects of drugs like cocaine and amphetamine?

00:42:52.580 And then second, if you put someone in a chronic state of activating that brain area, say you

00:42:59.080 did that by teaching them to approach their fears rather than to run from them, would

00:43:03.860 that produce epigenetic changes that would transform them physiologically?

00:43:08.300 Okay, so both very important questions.

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00:44:18.900 The dopamine system is absolutely critical here.

00:44:24.680 In the animal studies, we identified, because we could place tracers in the brain and measure

00:44:28.140 connections, that indeed, this brain area in the midline thalamus connects directly to

00:44:32.900 the major hubs of dopamine release in the brain.

00:44:35.720 They have names like nucleus accumbens, et cetera, ventral tegmental area.

00:44:39.200 Right.

00:44:39.360 So that was great, because it confirmed for us that...

00:44:41.540 So it is tapping the primary approach-related positive reward system.

00:44:45.300 That's right.

00:44:45.700 But it's a very major nucleus that allows that to happen, particularly in the face of

00:44:50.620 voluntary approach to feared stimuli.

00:44:52.620 That's exactly right.

00:44:53.600 And one thing about the dopamine system that's so important and also explains a lot of pathology,

00:44:58.680 but also a lot of human evolution, is that we have basically one major reward system,

00:45:04.540 which is the dopaminergic system.

00:45:05.920 You know, I sometimes like the analogy that, you know, nowadays you hear about cryptocurrency

00:45:10.540 or the dollar versus the euro versus the this versus the that.

00:45:14.340 There's only one currency in all of reality, actually, and it's dopamine, whether or not

00:45:18.900 it's the dollar back to dopamine or it's euro back to dopamine or Bitcoin back dopamine.

00:45:23.360 In the end, whether or not someone has a billion dollars or two dollars is really that currency

00:45:30.020 resides as something that's transacted in the real world, but their notion of power and

00:45:35.160 potential is dopaminergic.

00:45:37.200 And so, too, the potential for mates, the potential for food, how much food you have, you know,

00:45:41.360 how much meat you have stored in the freezer tells you a lot about your security and well-being

00:45:45.920 for you and your family.

00:45:46.880 Right.

00:45:47.500 And that's but and that is translated into a dopaminergic internal representation of how

00:45:53.420 safe and secure you are, et cetera.

00:45:56.160 So this system of fear versus confrontation taps directly into the dopaminergic system.

00:46:01.620 And there's a beautiful set of studies that were done in the 1960s, published in the journal

00:46:06.460 Science, as you know, one of the you know, one of the top journals to publish in.

00:46:09.920 Again, this is not work that that I did, but where they gave people, human beings, the

00:46:14.780 option to stimulate a number of different brain areas just sitting in the clinic.

00:46:18.460 And some brain areas would evoke feelings of drunkenness, others would evoke feelings

00:46:22.880 of of anger, others of sadness, others of sexual arousal.

00:46:27.180 And the area that these subjects all prefer to stimulate the most, in fact, they would just

00:46:32.240 sit there and lever press pretty much all day long was this midline thalamus area.

00:46:36.500 And the subjective feeling that they reported, I find this interesting and would love your thoughts

00:46:41.720 on this, is one of mild frustration, anticipation of something, although they didn't know what.

00:46:48.680 Anticipation.

00:46:49.120 And it's this idea, I think, that it's tapping into the dopamine system.

00:46:53.420 And the dopamine system...

00:46:55.340 The dopamine system says something good is going to happen.

00:46:57.960 That's right.

00:46:58.560 The key...

00:46:59.100 Something good is going to happen.

00:47:00.260 Something good is going to happen.

00:47:01.560 And it's an appetitive state in some sense, because it doesn't signify the acquisition of...

00:47:08.600 It's not satiating.

00:47:10.100 It's appetitive.

00:47:10.800 That's right.

00:47:11.360 And so it drives you forward.

00:47:12.600 And you might think that being driven forward would be unpleasant.

00:47:16.260 But if you're, in some sense, if you're activating the systems that drive you forward voluntarily,

00:47:21.680 then that's the most positive form of positive reinforcement you can have.

00:47:25.960 I think I read animal researchers who said that when they watched animals who were bar pressing

00:47:32.000 to receive stimulation in those brain areas, the animals would look forward as if something

00:47:38.500 was about to appear that they wanted to have appear.

00:47:41.100 Incredible.

00:47:41.660 So that was part of that apprehension.

00:47:43.680 It's a hope system in some sense.

00:47:46.160 It's the elicitation of hope.

00:47:47.500 That's right.

00:47:48.060 You know, it's dopamine.

00:47:49.900 And here I'm robbing words from others, like my colleague Anna Lemke, who, you know, it's

00:47:53.820 not about having.

00:47:54.980 It's about wanting.

00:47:56.180 It's not about pleasure as much as it is about craving and motivation and drive.

00:48:01.060 And something critical about that.

00:48:02.460 And Panksepp called it seeking.

00:48:04.780 Yeah.

00:48:05.080 Brilliant.

00:48:05.780 Brilliant.

00:48:06.600 I never met Panksepp.

00:48:07.720 Did you?

00:48:08.100 I did you ever.

00:48:09.020 You met Yuck?

00:48:10.020 I met him.

00:48:10.860 I met him online.

00:48:11.980 We were in a neuro.

00:48:13.220 We were in a neurological chat room, so to speak, for a neuropsychological chat room for

00:48:17.240 about five years.

00:48:18.080 And I had a chance to interact with him a fair bit in that.

00:48:21.600 So that was really good.

00:48:22.660 I'm envious.

00:48:23.000 He's done beautiful work.

00:48:24.460 And thank you for calling people's attention to his work.

00:48:26.940 I know you've done that many times and such key work.

00:48:30.740 The dopamine system is in touch with the autonomic system, sure, because it has to register

00:48:35.760 success versus failure of some pursuit.

00:48:39.220 The prefrontal cortex is actually part of the dopamine reward system.

00:48:42.620 People often overlook this.

00:48:44.340 And then we just think about nucleus accumbens and ventral tegmental area.

00:48:47.680 But the prefrontal cortex, because, as you pointed out before, it is generating possible

00:48:52.820 outcomes, different rules, different selves are being projected into the future.

00:48:56.940 You can think that the two marshmallow tasks, the classic, you know, give kids the option

00:49:01.920 to either have a marshmallow now or wait and have two marshmallows.

00:49:05.200 And the cute little videos of the kids, you know, in the room with the marshmallow, sniffing

00:49:09.360 it, talking to it.

00:49:10.260 Occasionally, a kid will just stuff it in his mouth.

00:49:12.240 Another child will turn away, you know, delightful, right?

00:49:16.020 And all sorts of ideas have come about how they do in life versus if they can wait or not

00:49:21.480 wait.

00:49:21.720 In any case, that's dopaminergic anticipation.

00:49:24.600 The key thing with dopamine, I think, that encapsulates the most of it is this notion

00:49:28.640 of reward prediction error, which is very simple.

00:49:31.180 If you are excited and anticipating something, you are generating some internal sense of the

00:49:36.680 probability of it happening.

00:49:37.940 We're going to the ice cream store, kids.

00:49:39.380 Let's go.

00:49:40.120 We're going to have ice cream.

00:49:40.820 We have ice cream.

00:49:42.180 It's closed.

00:49:43.100 The disappointment that they experience actually brings them far lower than they would feel,

00:49:51.300 much more sad than they would feel than had you not told them you were going to get ice

00:49:55.860 cream, which speaks exactly to what you were saying, that it's an anticipation signal.

00:49:59.800 So dopamine is going up, up, up.

00:50:01.040 We're going to get ice cream.

00:50:01.820 And then no.

00:50:02.640 So it drops below baseline.

00:50:04.280 They would have been better off being not told they were going to the ice cream store.

00:50:07.000 Just drive right by away.

00:50:07.940 The danger of hope.

00:50:08.960 The danger of hope.

00:50:09.520 If you anticipate that it's going to be open, and again, this could translate to any scenario

00:50:14.500 and it's open, there's a dopaminergic signal upon receiving the reward, but it then drops

00:50:21.060 a little bit.

00:50:21.920 This is the basis of addiction, actually.

00:50:23.700 Drops a little bit below baseline transiently.

00:50:26.260 So we always think of the ice cream is the reward.

00:50:29.040 Well, actually, the reward was right before you had that first lick of ice cream because

00:50:32.560 you know you're going to get it.

00:50:34.220 This is also true of sexual behavior.

00:50:35.860 It's true of people who sell a company or they're anticipating something exciting or

00:50:42.020 of a wedding.

00:50:42.940 It also sort of partially explains this notion of postpartum depression, where people are

00:50:48.820 so excited about something, the delivery of a child or something on the arrival, and then

00:50:52.220 for some reason they feel let down.

00:50:53.940 It's because the anticipation was that great.

00:50:56.680 So many, many scenarios.

00:50:58.300 There might be an exhaustion component there, too.

00:51:00.320 Well, it's also the case, if I remember correctly, that that dopamine kick, so imagine what it

00:51:06.900 does is backtrack the neural systems that were activated as the reward was approached.

00:51:15.080 So then it feeds back reinforcement, not reward, but mediates cellular growth and maybe myelinization.

00:51:25.400 It's increasing the efficiency of the neural connections of the systems that were activated

00:51:30.140 just prior to receiving that reward in the order they were prioritized, in the order they

00:51:35.520 were manifested.

00:51:36.600 So the closer the behavior is to the receipt of the reward, the more it's reinforced and

00:51:41.560 more likely to be manifested in the future.

00:51:43.620 And then there's a decay function going back in time.

00:51:46.200 And so, and that's partly how an addictive sub-personality can grow, too, right?

00:51:52.960 Because you can imagine that there's a certain state of mind that you're in.

00:51:56.200 Maybe it's a state of something approximating nihilistic hopelessness that grips you every

00:52:01.620 time you're motivated to seek out your favorite drug.

00:52:04.540 And that's fairly far back in the activation chain, but it's there every time you take a

00:52:08.740 hit.

00:52:08.980 So what happens is the dopaminergic reinforcement produced by the drug reinforces that nihilistic

00:52:15.840 hopelessness that drives the drug-seeking behavior.

00:52:18.580 And that's how, in part, you develop a monkey on your back.

00:52:21.220 Yeah, I love the example, even though I am sad that it happens for people.

00:52:26.760 I love the example because what you're saying is that, and it's exactly right, that the memory

00:52:32.340 for events and states of mind and emotions that preceded a successful collection of reward

00:52:39.180 or arrival at reward is set into a huge number of motor commands, some of which are subconscious.

00:52:46.460 And the ultimate dopamine signal, actually, I experienced this the other day.

00:52:52.180 I can give an example.

00:52:53.900 My girlfriend and I decided to go to the beach.

00:52:55.780 We were going to do this little ritual that we've been talking about doing for a while.

00:52:59.280 And I had on a piece of paper what we had written out we were going to do.

00:53:01.940 And I had it in my back pocket.

00:53:03.660 And we got to the ocean.

00:53:05.300 And the sun was setting.

00:53:06.260 It was sort of perfect timing for this.

00:53:07.900 And the piece of paper was gone.

00:53:10.220 And I thought, oh, my goodness, how did I screw this up?

00:53:12.300 Like, of all the things, you know, I'm supposed to, you know, I'm 47 years old.

00:53:18.260 This is not like I should be able to do this.

00:53:20.400 You know, I blew it.

00:53:21.780 I blew it.

00:53:22.360 So I went back to the car, long walk, looking everywhere.

00:53:25.060 It was not a windy day.

00:53:26.140 But I thought, gosh, where's this piece of paper?

00:53:28.180 Looking around, didn't find it.

00:53:29.200 Went all the way back to the car.

00:53:30.120 Wasn't the car.

00:53:30.680 Came all the way back.

00:53:31.280 And I was walking toward her.

00:53:32.320 I saw her.

00:53:33.100 And I thought, okay, this is really embarrassing.

00:53:35.460 I'm going to just have to wing it or remember.

00:53:37.500 We didn't have our phones intentionally either.

00:53:39.360 So we couldn't look it up.

00:53:40.760 And then I saw the piece of paper on the beach.

00:53:44.140 And it was partially buried in the sand.

00:53:45.600 I picked it up.

00:53:46.220 And I was elated.

00:53:47.700 What happened there was my dopamine had dropped way below baseline.

00:53:51.780 Because I was disappointed that I'd lost it, disappointed in myself, et cetera.

00:53:56.240 And then I found it.

00:53:57.080 Right.

00:53:57.420 And so your anticipation was for nothing.

00:53:59.560 Exactly.

00:54:00.080 So you got punished by yourself for that.

00:54:02.060 Exactly.

00:54:02.380 Because that should be eradicated.

00:54:03.580 If you're highly anticipatory and it doesn't make itself manifest, then you were seriously wrong.

00:54:09.120 So you're going to take an emotional hit as a consequence of that.

00:54:12.040 I think that's also associated, that emotional hit, that pain that you feel.

00:54:16.480 I think that's actually associated with the beginning stages of the death of the systems that mediated that initial response.

00:54:23.940 Because you should eradicate systems that make you anticipate that don't work.

00:54:28.960 Right.

00:54:29.220 And that means those systems, which are already instantiated and alive in some sense, have to decay and die.

00:54:35.240 And it strikes me as highly probable that you're going to pay a price in something approximating pain for the death of those malfunctioning systems.

00:54:43.260 It's also why, because why wouldn't they fight for their lives to some degree?

00:54:46.940 Why wouldn't they resist the decay and death that might be necessary to keep you going?

00:54:51.520 There should be some pain associated with that logically.

00:54:54.300 Because it is a biological transformation.

00:54:56.760 Yeah, it's an interesting way, a lens to view it through.

00:54:59.240 That that self-image that I had in that moment of, you know, I'm the responsible partner who can take care of a simple thing, right?

00:55:05.900 For this nice little ritual that we've been talking about doing for a while.

00:55:09.360 I failed, right?

00:55:10.340 Well, it's also so interesting.

00:55:12.780 You think about that.

00:55:13.480 This is a depressive cascade, eh?

00:55:15.940 And it's very hard to bind.

00:55:17.660 Because imagine you anticipate something, and then you make a mistake.

00:55:21.000 Now, the question then becomes, how significant is the mistake?

00:55:25.700 And one view of your error would be, well, the paper blew out of my pocket, and that could happen to anybody.

00:55:32.160 And the more catastrophic interpretation would be, and it's an extension of the thought path that you started to walk down.

00:55:39.240 Well, I'm near 50 years old.

00:55:40.960 I should be much more responsible than this.

00:55:43.440 And there's something wrong with me as a person.

00:55:45.600 And then a depressive person would go even further.

00:55:47.860 They'd say, well, not only is there something wrong with me in this decision, this is a decision like every other decision I make right now.

00:55:55.500 I never make a good decision.

00:55:56.820 In the past, I've never made a good decision.

00:55:59.220 And there's no way I'm going to change in the future.

00:56:01.760 And so the depressive takes that punishment response, let's say, that's a consequence of failed anticipation, and can't bind it.

00:56:10.920 And it just takes out all of their potential future selves.

00:56:14.780 That's a good way of thinking about it.

00:56:16.040 Yeah.

00:56:16.320 And so then they're in a depressive pit.

00:56:18.180 Yeah.

00:56:18.660 So that's too much learning from failure.

00:56:21.320 Right.

00:56:21.640 That's it.

00:56:22.720 I'm really grateful for your insight on this.

00:56:26.940 Because indeed, if I'm honest, my thought train went to the point of, you know, I didn't think, oh, I'm a total failure because I lost this piece of paper.

00:56:34.660 I thought to myself, well, you know, if it were a priority, I would have ensured I wouldn't have lost it.

00:56:40.520 Right, right.

00:56:40.980 She'll interpret it as not being a priority.

00:56:42.700 Like, where are my priorities?

00:56:43.900 Am I, you know, am I overspent?

00:56:45.640 You know, like, what's going on?

00:56:47.160 You start to sift into the full set of questions.

00:56:50.600 And then, of course, finding the paper resurrects the sense of self.

00:56:55.620 It was, you know, I think it was in that movie Pulp Fiction.

00:56:57.900 Yeah, well, that binding problem is really tricky, eh?

00:57:00.520 Because, so, there's some good rules of thumb for that, which is one of the rules of thumb for that that's extremely useful, that's socially instantiated, is innocent until proven guilty.

00:57:13.820 Right, so you might say when those thoughts come up, because they're adversarial and accusatory thoughts, you might say, well, that is part of the realm of possibility.

00:57:21.640 But I shouldn't, when your child does something wrong that's minor, you don't say you're a rotten kid.

00:57:28.100 Right?

00:57:28.540 You say, you bind it, you say, look, kid, here's a bunch of things you're doing right.

00:57:34.640 But in this particular example, this specific situation, here's the minimal thing you did incorrectly and how to alter it.

00:57:42.780 And it's a really good habit of mind, it's like, to address towards yourself as well as to other people, which is to say, well, what's the minimum crime that I am responsible for in this moment?

00:57:52.680 And that's part of this miracle of the presumption of innocence, and especially without proof.

00:57:58.600 A lot of what I did in my clinical practice to people who had a depressive temperament was help them make a case for themselves.

00:58:04.300 It's like, well, maybe you're as bad as you think you might be, but maybe not.

00:58:10.180 Let's take the contrary argument, let's make you as innocent as you can be in this situation, and only narrow the repair to the absolute minimum that needs to be manifested.

00:58:21.180 Now, some people don't have that problem because they don't have a depressive state of mind, let's say.

00:58:26.480 They're somewhat resilient to the cascading effects of punishment.

00:58:30.460 Those are people who are low in trait neuroticism, by the way.

00:58:33.380 So you could think of trait neuroticism as an index to which the degree failure co-activates punishment across a whole sequence of nested selves.

00:58:45.760 The higher you are in neuroticism, the more likely a given error is to cascade up the hierarchy of possible selves.

00:58:54.280 And it's a trade-off because sometimes when you make one little mistake, it is actually an indicator of a flaw in your character.

00:59:00.460 But most of the time it isn't.

00:59:02.380 And it certainly can't be responded to that all the time because then you'd never be able to make a mistake without wiping yourself completely out.

00:59:09.560 And that's obviously not helpful.

00:59:10.900 Is it fair to say that, at least in the raising of children and maybe in the raising of ourselves, that we should, as much as possible, try and emphasize that errors are due to state, not trait?

00:59:23.720 Yes, absolutely.

00:59:25.220 And you do that in an argument with your wife as well.

00:59:29.360 You want to make it as local and precise as you possibly can.

00:59:34.660 And that's also one of the advantages to removing yourself from a rage or an anxiety state.

00:59:41.180 Because a rage or an anxiety state is low resolution and global.

00:59:45.380 And so it'll be globally accusatory.

00:59:47.860 And so you want to specify it and you think, okay, well, what's the minimum necessary behavioral transformation to ensure that similar mistakes are not replicated in the future?

00:59:59.840 And generally that doesn't require, like, read.

01:00:02.620 It's like if your roof leaks, you don't have to dig a new foundation.

01:00:05.720 You can just fix a few shingles.

01:00:07.060 And you might think, well, the rain's coming through, so you have to tear down the whole house.

01:00:10.460 It's like, well, no.

01:00:12.060 You have to.

01:00:13.240 And you might panic and run around because the water's coming in.

01:00:15.880 But it's still a bad idea to dig up the foundations every time something trivial maintenance problem needs to emerge.

01:00:21.820 And so one of the things that's very useful to learn is, like, well, is this only a trivial maintenance problem?

01:00:28.520 And one of the advantages to that, too, is that if it's not the collapse of your entire self, let's say, and it's a trivial maintenance problem,

01:00:36.000 you're much more able to activate that courageous response to anomaly that's part and parcel of exploratory behavior and eventual success.

01:00:44.420 So when part of the trick of many sorts of, well, I would say religious training enterprises,

01:00:51.000 certainly the meditative enterprises, is something like, how do you tell yourself a story, like a real story,

01:00:57.660 though a story that actually works, that's most likely to put yourself in a position where you can confidently approach the thing that's blocking your path?

01:01:08.760 This notion, you brought up three points that I think immediately of the related neurology,

01:01:14.420 but I'm going to repeat them back to make sure I understand because they're very salient in my mind right now,

01:01:18.860 which is this notion of the prefrontal cortex trying different versions of self and working with,

01:01:25.320 contending with bodily states in those moments.

01:01:28.800 And the sort of either death or, you know, or growth or resurrection of those different selves, depending on the outcomes.

01:01:39.440 Right, right.

01:01:39.860 The next, this notion of state or trade I find fascinating.

01:01:43.440 You know, after I found that piece of paper, I felt like I was like the greatest, you know,

01:01:47.360 I got this huge dopamine surge because it's, it's the Delta.

01:01:49.840 It's the difference between your baseline and the P.

01:01:51.940 Yeah, right.

01:01:52.400 So even though I'd lost it, right.

01:01:53.780 I mean, I should have thought, oh gosh, I wasted 30 minutes of our time.

01:01:56.600 But instead I thought I found, I found this amazing.

01:01:59.500 And I felt so elated.

01:02:00.920 I think there was a, it was the movie Pulp Fiction.

01:02:03.020 I think it was the John Travolta character said something, I'm going to get this wrong.

01:02:05.680 But, you know, he said it was almost worth losing that just to find it again.

01:02:10.040 He was talking about something, I forget what it was, and I think that captured it there

01:02:13.640 as well.

01:02:14.840 And then my question is, however, is, you know, we've been talking about if you lose something

01:02:19.960 or if an outcome was not great, how that can fan out into a kind of over-interpretation

01:02:25.240 of traits and this kind of depressive neurotic interpretation.

01:02:28.420 What about the opposite where certainly for every success that one has, you know, like

01:02:34.720 for instance, if I had not dropped this piece of paper, I wouldn't have thought of it as

01:02:38.580 a great success.

01:02:39.380 I would have just thought of it as what I was required to do in that moment, right?

01:02:43.360 It was sort of just duty, right?

01:02:44.980 And I'm not somebody who celebrates with everything I check off my list.

01:02:50.280 I, you know, sometimes, yes, there are bigger, bigger things than others, bigger achievements

01:02:54.580 than others, but I can imagine that certain people might over-inflate their wins.

01:03:00.280 Manics.

01:03:00.800 Manics over-inflate. 1.00

01:03:01.880 Well, there it is.

01:03:02.700 You bet.

01:03:03.080 So, well...

01:03:03.440 The dopamine system.

01:03:04.260 Yeah, well, for a manic, every possible self is wonderful simultaneously.

01:03:09.300 And so they're completely fragmented, right?

01:03:12.040 Because every possibility is 100% dopaminergically, giving them a dopaminergic kick.

01:03:18.240 And so it's complete positive emotion catastrophe on the manic side.

01:03:24.460 So these systems, they have to exist in such tight balance, right?

01:03:28.000 Because all of your potential positive selves are not to be regarded with exceptional enthusiasm.

01:03:34.340 That's a form of pathology.

01:03:35.840 Even though, like, people don't like being treated for mania often because especially

01:03:40.840 going into a manic state is very enjoyable because it is associated with enthusiasm.

01:03:46.000 And that's all dopamine-mediated positive emotion.

01:03:50.820 But there are problems with positive emotion.

01:03:54.680 And one is, well, it needs to be judicious and differentiated.

01:04:00.380 You shouldn't be positive about everything, which is why you shouldn't reward children

01:04:04.020 indiscriminately.

01:04:05.080 It has to be targeted.

01:04:06.660 And so when a system loses its focus and target, its capacity to discriminate, then it

01:04:12.320 becomes pathological.

01:04:13.240 And people don't often think of pathologies of positive emotion, but mania is definitely,

01:04:17.880 that's definitely what it is.

01:04:19.260 And it makes people impulsive, too.

01:04:22.140 And fragmented even in their speech.

01:04:24.660 Someone who's really manic is a different person every sentence.

01:04:30.240 It's interesting because one thing that we know, again, about the dopamine system, it's

01:04:34.820 about anticipation.

01:04:35.740 The other thing that is absolutely clear about the dopamine system is that it is tacked to

01:04:43.280 pursuit more than it is to outcomes, but it is highly subjective to interpretation.

01:04:50.160 And this is exciting, actually, and holds great possibility.

01:04:52.880 I mean, putting mania aside, when dopamine is elevated, it tends to put our perception to

01:04:59.340 things outside of our, I would say, beyond the confines of our skin.

01:05:03.160 That person, you know, that potential lover or mate, that food, that reward, that thing.

01:05:07.840 Yeah, that target.

01:05:08.560 It's all about that target.

01:05:09.760 And I think this explains why manics are all about plans in the future.

01:05:13.100 I'm going to do this, and I'm going to be president, and I'm going to do that, and et

01:05:15.480 cetera.

01:05:15.700 Yeah, you see the opposite in neuroticism, because one of the cognitive phenomena that

01:05:24.520 loads very heavily on neuroticism is self-consciousness.

01:05:28.300 And so when you fall into anxiety, then there is this internal obsessiveness, which has to

01:05:33.460 do with the panoply of sins, in some sense.

01:05:37.420 Which parts of me are malfunctioning and need to be eradicated?

01:05:40.980 And one of the things I used to do with my socially anxious clients, so they would go

01:05:45.280 into a social situation, often with eyes downcast, by the way, and they would be so intensely

01:05:51.800 concentrating on their own internal sensations that they would fail to make eye contact with

01:05:57.040 anybody they were talking to.

01:05:58.500 And then they would be awkward, because they weren't reading the cues they could have read

01:06:02.700 if they would have only looked.

01:06:04.380 And then the conversation would become disjointed, and then they would get anxious and fall into

01:06:09.640 themselves, and then it would just spiral.

01:06:11.320 I see.

01:06:11.760 And so one of the things that I taught them to do wasn't to try to calm themselves down,

01:06:17.740 but to try to calm the other person down.

01:06:20.160 So when you go into a social situation, pay more attention to the other person.

01:06:25.260 Like, just focus your attention outward.

01:06:27.520 And if the person had any social skill, sometimes I had clients who had no social skills, and so

01:06:32.860 they were anxious socially, because they actually didn't know how to behave socially.

01:06:36.640 And so then you had to teach them the social skills.

01:06:39.240 But some of them had the skills, but wouldn't activate them, because they were so neurotically

01:06:43.900 obsessed with their own inadequacy, that they failed to attend to the cues that would elicit

01:06:50.640 the proper responses.

01:06:52.100 And all they had to learn to do was watch.

01:06:54.980 And then they would automatically respond, because they knew how to have a conversation.

01:06:59.480 This brings us to some of the practical tools that I think my laboratory has been working

01:07:04.320 on, which is, you know, many people have heard about the utility of mindfulness meditation,

01:07:07.620 which most typically is close your eyes, focus on third eye center, your breathing, you know,

01:07:11.920 bring your awareness to your so-called interoception.

01:07:14.780 You know, perception can be interoceptive from the skin inward, or exteroceptive to the world

01:07:19.400 outward.

01:07:20.260 The data are showing that people who are overly socially anxious, for instance, they are too

01:07:27.420 much in touch with their bodily signals.

01:07:29.880 In fact, they can count their own, they can count their own heartbeats without taking

01:07:33.520 their pulse with their finger, which is a high, which is a great indicator of how interoceptively

01:07:38.400 aware you are.

01:07:39.340 Those people would probably be best to avoid inward focusing, excuse me, meditations.

01:07:45.440 Well, well, it's hard to say, because there may be a variable there that's relevant.

01:07:51.680 See, the reason that socially anxious people are so interoceptive is it's involuntary, right?

01:07:57.380 They get gripped by the negative emotion, and then that produces this intense, obsessive

01:08:03.120 interoception.

01:08:05.240 That might not happen if they did it voluntarily.

01:08:08.100 I see.

01:08:08.780 Right?

01:08:09.360 Because you're going to activate an entire different system, the one you already talked

01:08:12.500 about.

01:08:13.500 This is why exposure therapy works so well in psychotherapy.

01:08:17.280 It's like, well, I'm afraid of something, and if I go near it, then I'm possessed by negative

01:08:21.740 emotion.

01:08:22.740 Well, that's if you go near it accidentally.

01:08:25.140 I'm going to have you go near it purposefully, and what you're going to find is that to the

01:08:29.840 degree that you do it purposefully, that response will be quelled, and that happens.

01:08:35.500 It's extraordinarily reliable, and it does seem to be—this is why I was wondering about

01:08:40.000 gene expression.

01:08:40.900 So imagine that you have someone who's habitually avoidant, and maybe they're avoidant because

01:08:45.640 when they become possessed by negative emotion, they become hyper-aware of their internal state,

01:08:50.540 and they feel the panic, and so then they freeze or retreat, and they do that constantly.

01:08:56.780 And so—and then they're in this terrible negative emotional state all the time because

01:09:02.000 every time they see a stimulus that's associated with retreat, they get gripped by these interoceptive

01:09:07.080 sensations.

01:09:09.200 And so you say to them, well, we're going to reverse that instead of you being gripped

01:09:13.840 by that, by fiat, by the command of these underlying systems, you're going to expose yourself to

01:09:20.840 that voluntarily.

01:09:21.480 Now, you could imagine that what you're doing is imposing the dominance of that nucleus reunions

01:09:27.620 on the anxiety-provoking systems.

01:09:31.600 And so I'm wondering—see, if you do that repeatedly with people, not only do they stop

01:09:37.260 being afraid of the things that you're showing them, that you're exposing them to, but they

01:09:43.300 become more likely to approach other things they're afraid of, far more likely.

01:09:47.620 In fact, it doesn't exactly look like people get less afraid at all.

01:09:51.860 It looks like what happens is they learn to get braver, and that generalizes.

01:09:56.680 And so I was wondering, when I was reading your research today, is it the case that if

01:10:00.780 you put someone in chronically and voluntarily into a state where, let's say, the nucleus

01:10:05.520 reunions is activated, that that transforms their character at the genetic level so that

01:10:12.260 that's more likely to be the case in the future?

01:10:14.340 So it really retools them all the way down to the DNA.

01:10:16.980 Yeah.

01:10:18.180 Incredibly important question.

01:10:19.780 It's the question.

01:10:21.160 Again, you're asking the exact questions that we're pursuing now.

01:10:25.600 Now, and here's the answer.

01:10:27.660 There are two modes of changing these responses in the neural circuitry.

01:10:31.600 One lies in so-called neuroplasticity, which could be strengthening of synapses or just

01:10:36.500 reordering of nerve connections.

01:10:38.220 Could be the addition of new cells.

01:10:39.620 There's a lot of excitement about the addition of new neurons, but really that only reflects

01:10:43.400 a small percentage of changes in the brain of adults.

01:10:46.600 It's actually more of the rewiring of existing connections.

01:10:48.940 But the mechanism doesn't matter so much.

01:10:50.620 Something gets rewired such that the response is then different going forward.

01:10:54.820 And indeed, that happens.

01:10:56.140 Any system that taps into the dopamine system, and indeed, everything we're talking about

01:11:01.000 today does, is highly subject to reward-induced neuroplasticity.

01:11:07.160 Yeah.

01:11:07.360 In fact, so much so that some of the best experiments done on this have shown that if you give somebody

01:11:12.360 a drug that transiently increases dopamine, works better if you also transiently increase

01:11:17.900 acetylcholine or something like that as well.

01:11:20.120 But for the next hours, you know, one to four hours, the neuroplasticity is scaled up, right?

01:11:27.600 It takes many fewer trials or many fewer cognitive behavioral therapy sessions.

01:11:32.900 This has only been done a few times.

01:11:34.200 There are many fewer learning sessions to create a permanent shift in the neurology such

01:11:38.880 that...

01:11:39.060 Okay, so does that mean that if you believe when you are at the outset of a task that

01:11:44.100 you're doing something important, so you're approaching a valued goal, and you have a lot

01:11:49.300 of anticipation as a consequence of that, does that mean that you put yourself in a neurochemical

01:11:54.080 state that facilitates learning?

01:11:56.460 Absolutely.

01:11:57.440 Without question.

01:11:58.060 So if you believe what you're doing is important, if you truly believe that because it's related

01:12:01.840 to an important goal and it's a pathway forward, then that's going to transform into a manifestation

01:12:06.920 of neuroplasticity.

01:12:07.920 Absolutely.

01:12:08.600 And every time I hear about the sort of, you know, woo statements about, you know,

01:12:13.340 you know, I don't want to offend anyone here, but sure, I'll just say, you know, you hear

01:12:16.500 about the secret or manifesting or intention, all of that is really, it's capturing a fundamental

01:12:22.100 principle of the way that our neurology works, which is that the prefrontal cortex as a rule

01:12:27.240 setting, but flexible rule setting machine that taps into the dopamine system can absolutely

01:12:33.540 adopt new rules for reward release in the brain.

01:12:37.660 Again, there's basically only one reward system.

01:12:39.960 There's also serotonin system, as you know, but the dopamine system is the major currency

01:12:44.000 of reward.

01:12:44.540 So much so that, for instance, everyone knows that food is rewarding.

01:12:49.540 We anticipate food.

01:12:50.480 We eat a delicious steak or something, and we feel rewarded.

01:12:54.280 However, if you are somebody who can attach thoughts such as fasting is good for me, I'm

01:13:01.140 going to do intermittent fasting, or I'm not going to eat those foods, and therefore, I'm

01:13:04.940 going to attach my thinking to the rewards that will come with better health, better aesthetics,

01:13:09.080 et cetera.

01:13:09.300 The dopamine system responds.

01:13:12.220 It's not just a belief in a narrative.

01:13:14.320 It's a real response.

01:13:16.160 And what actually starts to happen is that people start to enjoy the foods that they are

01:13:21.640 restricting themselves to more.

01:13:23.840 There are actually beautiful data on this from my colleague, Ali Crum's laboratory at Stanford,

01:13:28.720 that if you believe a food is nutritious and good for you, it actually has better impact

01:13:35.520 on your physiology.

01:13:36.440 Of course, there are the rules of physiology and nutrition that still apply, right? 0.91

01:13:40.460 You can't tell yourself that the garbage is good for, right?

01:13:43.360 But there's a significant scaling up of the positive response that's associated with dopamine

01:13:47.840 and hormonal cascades, which we can talk about in a moment.

01:13:50.840 In the same way, if one adopts a sort of a Carol Dweckian growth mindset approach, okay,

01:13:56.400 it's not about receiving the reward that the more strain I feel, the more effort that I'm

01:14:02.060 putting in, the closer I'm getting to my goal.

01:14:04.060 That over time will become a rewarding state such that one will pursue states of reach.

01:14:10.100 Yeah, well, it should be also proportional to the magnitude of the goal.

01:14:15.560 That's right.

01:14:16.380 Right?

01:14:16.700 And so this is, I think, why people are so obsessed in some sense with the search for

01:14:22.420 fundamental meaning.

01:14:23.960 It's because you want to be able to associate.

01:14:25.780 So imagine, this is a good story.

01:14:27.500 So you can imagine two people laying bricks, they're building a gigantic wall, and the

01:14:32.480 one person thinks, oh my God, you know, this wall is going to take 100,000 bricks, and I'm

01:14:37.840 laying one at a time, and I'm wasting my life away, trivially adding to this gigantic brick

01:14:44.300 wall.

01:14:44.760 And what am I doing?

01:14:45.700 This is absolutely miserable, brick by brick.

01:14:48.940 And the other person thinks, in 300 years, this is going to be a cathedral.

01:14:54.700 And so the person in the second state is doing exactly the same thing at a local level, laying

01:15:00.260 bricks.

01:15:00.720 But each brick is related to a very high goal.

01:15:04.160 And that means the reward that's attendant upon the laying of the brick is proportional

01:15:08.560 to the goal, to the aim of the entire behavioral process.

01:15:15.040 And so it seems to me, so if you're aimless and goalless, and I know you've done some work

01:15:19.940 on goal setting, if you're aimless and goalless, then you can't elicit any positive emotion.

01:15:25.520 And if your goals are fragmented, which is also what happens if you're aimless or your

01:15:30.280 goals lack unity, if your goals are fragmented, then no given behavioral manifestation can elicit

01:15:35.780 any dopaminergic reward, because it's not a step forward to anything desirable.

01:15:40.760 And so there's no positive emotion.

01:15:43.440 And so you can't learn.

01:15:44.640 Well, according to your account, I didn't know that.

01:15:47.380 See, I didn't know that when you put yourself in a state of apprehension in relationship to

01:15:51.880 a valued goal, that your neuroplasticity improves and you can learn better.

01:15:55.940 That's very, very cool.

01:15:57.560 So, because, you know, I just developed this app for writing called Essay.

01:16:01.040 And one of the things we do is we tell people that when they sit down to write an essay,

01:16:08.300 that's the most important thing you have to do, is you have to have a question in mind

01:16:12.400 that you regard finding the answer to as worthwhile.

01:16:17.180 Otherwise, the whole exercise is a lie.

01:16:19.940 So even if you're assigned a topic, you have to find something within the topic that grips you

01:16:24.740 and provides you with the motivation that's appropriate to move forward with the essay,

01:16:30.260 with the attempt.

01:16:31.920 And it is a lie otherwise.

01:16:33.540 You're wasting your words.

01:16:34.860 You're engaging in futile activity.

01:16:37.500 And you're going to write something dull and terrible, and it's going to frustrate you

01:16:40.320 and bore you while you're doing it.

01:16:41.540 And that's because your own nervous system is telling you that you're participating in something

01:16:44.980 that you have no belief in.

01:16:47.640 And so, but if you do, if you're gripped by the questions, like,

01:16:50.680 God, I really want to answer this question.

01:16:52.460 It's like, well, you're in a perfect condition to begin to write an intelligible essay

01:16:56.580 because you actually want the answer.

01:16:58.740 And then the writing exercise is going to be gripping because you're grappling with a real mystery.

01:17:04.180 And that's so cool if doing that also puts you in a state where you're much more likely to learn,

01:17:10.120 which makes sense, right?

01:17:11.100 Because if you're doing something important and you seem to be moving forward,

01:17:14.420 that's a really good time to learn.

01:17:17.040 Neurophysiologically, that would make, or evolutionarily, that would make perfect sense.

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01:18:35.620 Absolutely.

01:18:38.680 You know, the system, the dopaminergic system that we're talking about,

01:18:41.660 anticipation and then action and reward,

01:18:43.880 or in some cases, no reward, right?

01:18:45.860 And the ability to persist toward a goal regardless is a generalizable system.

01:18:51.100 You know, you had that chapter about, you know, get your room in order, right?

01:18:54.260 Get your belongings in order.

01:18:56.020 This is, I think, very relevant right now.

01:18:58.060 Even though it's important to have higher goals and lofty goals,

01:19:02.120 the dopamine system is an incredible system

01:19:05.040 because it is depletable and yet it's also renewable and it is self-amplifying.

01:19:11.920 What I mean by that is,

01:19:12.960 let's say that I'm somebody who doesn't know what I'm working toward.

01:19:15.980 I don't have a specific goal or question.

01:19:17.780 By completing even what seem like menial tasks,

01:19:21.760 like making myself a cup of coffee, drinking it, cleaning up completely,

01:19:26.000 drying the cup and putting it back in the cupboard.

01:19:29.000 What happens is if, even if you make that seemingly trivial goal, the goal,

01:19:34.340 in addition to making the kitchen look nicer, it completes a circuit.

01:19:38.860 It closes the dopaminergic circuit.

01:19:41.400 And when dopamine is released, and it will be, maybe not to the same extent as publishing

01:19:45.100 a novel, but to some extent, dopamine amplifies our ability to think into the future,

01:19:51.640 to make additional plans that are unrelated to what you just did.

01:19:56.740 And it literally increases confidence and energy.

01:20:00.900 Why?

01:20:01.920 Well, for the following reason.

01:20:02.960 We all think about caloric energy, but what most people are never taught,

01:20:06.500 you know, and if I had 10 things I could teach people, one of them would be

01:20:10.240 adrenaline, epinephrine is neural energy.

01:20:14.700 It's your ability to get up and go.

01:20:16.120 It's the thing that makes you jittery when you're a little nervous,

01:20:17.900 but it's also what allows you to move forward, to go out for a run,

01:20:20.900 to pursue any goal, cognitive or physical, et cetera.

01:20:25.220 Epinephrine, which is also adrenaline, those are the same thing,

01:20:27.460 is literally manufactured from the molecule dopamine.

01:20:32.340 If you look at the biochemical cascade, it is dopamine is converted into adrenaline,

01:20:37.820 which is the basis of all energy, all neural energy.

01:20:41.520 And so including thinking.

01:20:43.760 And so if one is not in a place of being able to set their goal on a particular lofty goal,

01:20:49.020 a graduate degree, a book, et cetera, yet the way one gets to that is by completing

01:20:53.540 things in their immediate environment from start to finish and closing the dopaminergic loop,

01:20:58.820 you literally.

01:20:59.420 Yeah.

01:20:59.640 Well, those are at least, those are at least micro narratives.

01:21:02.780 That's right.

01:21:03.820 Right.

01:21:04.120 So they're not integrated across a long span of time, but they're not nothing.

01:21:08.300 And so one of the things, well, I did write about this in my first book,

01:21:11.340 particularly about putting your life, putting your house in perfect order.

01:21:14.440 It's like, well, if you, if you're lost,

01:21:16.900 one of the things you can do is look around and see

01:21:19.700 what direction you could take locally is fix something.

01:21:23.500 And I used to tell my clients, this is a very good thing to know.

01:21:27.360 Find something that you could do that would make things better that you would do.

01:21:34.400 And there's a humility in that too, because especially if you're in a low energy state,

01:21:37.940 it's like, oh my God, you know, I don't have enough energy to make dinner.

01:21:40.940 It's like, do you have enough energy to put a fork on the table?

01:21:44.800 And sometimes people are so depressed that that's really all they can do.

01:21:47.640 It's like, can you take, can you take a small step forward, no matter how small that is?

01:21:53.720 And so that's, I didn't see, I knew that adrenaline was a by-product or

01:21:58.300 down the biochemical chain from dopamine, but I didn't get the significance of that fully.

01:22:05.900 So basically what you're saying is that if you implement a micro routine,

01:22:09.820 even something like washing a cup and putting it back in the shelf,

01:22:13.020 and you know, that's a good thing because you have a shelf and there's cups on it.

01:22:16.040 You've already decided that's an appropriate way to live is to have your coffee cups on a shelf.

01:22:21.740 If you go ahead with cleaning out the cup and putting it on the shelf,

01:22:25.300 then you've taken steps towards a valuable micro goal.

01:22:29.380 You get a dopamine kick from that, that transforms itself into adrenaline and energizes you.

01:22:34.800 Which then-

01:22:35.240 That's partly the reason that it has an antidepressant effect.

01:22:37.480 That's right.

01:22:37.780 And then you can lean into another behavior.

01:22:39.960 Some of the more successful classes of antidepressants, again, not for everybody,

01:22:44.220 are the ones of the dopaminergic, adrenalinergic variety, right?

01:22:48.980 Things like apriorone, as opposed to, you know, there's a lot of debate about SSRIs.

01:22:52.600 They tap into a different system.

01:22:54.100 You asked about gene expression changes.

01:22:57.420 There's neuroplasticity, which is on the short scale.

01:23:00.060 Completion of an even trivial task, like the putting away of the cup,

01:23:03.480 will give you more dopamine, would give you more adrenaline,

01:23:06.340 which in this analogy of either being back on one's heels, flat-footed,

01:23:10.080 or forward center of mass, regardless of where one is starting out,

01:23:13.040 let's say depressed is back on one's heels, it's going to tilt you forward a little bit.

01:23:16.340 And that's a question of what you do with it.

01:23:18.580 So the cognitive appraisal is critical.

01:23:20.880 Because again, with the prefrontal cortex being so critical

01:23:23.700 in establishing which of these loops gets repeated,

01:23:27.140 the cognitive appraisal is critical.

01:23:28.620 I'm somebody who can get things done, even if they're small.

01:23:31.880 Now, if you do the cognitive appraisal-

01:23:34.580 Or you can take another cognitive appraisal there, too,

01:23:37.840 which is small things are not small.

01:23:43.060 That's right.

01:23:44.740 Precisely for the reason that we just described.

01:23:46.580 It's like you might have the cognitive appraisal

01:23:49.140 that doing something local, like cleaning up your room, is small.

01:23:52.400 But it's not obvious at all that that's the case.

01:23:54.380 It's not that trivial to put your immediate surroundings in order.

01:23:59.260 And it can easily be the stepping stone to putting things in order on a broader scale.

01:24:03.740 In fact, it's probably the necessary stepping stone to do that.

01:24:06.900 And so they might seem small, but they're a step ahead.

01:24:11.060 And ahead is a good direction.

01:24:12.460 Absolutely.

01:24:12.820 And so they're not as small as you might think.

01:24:14.740 And so you can pat yourself on the back,

01:24:16.880 especially if you're depressed a little harder than you might otherwise.

01:24:19.320 By saying, you know, you say, well, this is trivial, but I did it.

01:24:21.520 It's like, no.

01:24:22.880 If you're moving ahead, tilting yourself forward in your metaphor,

01:24:27.260 that's not small.

01:24:28.200 You just keep doing that.

01:24:29.920 You're going to get out of this paralyzed or retreat mode.

01:24:34.020 And then God only knows what you're going to be able to do.

01:24:36.020 That's right.

01:24:36.360 And I think that if people were to look at these neurological and psychological processes,

01:24:40.500 because we're really talking about both, is as algorithms, right?

01:24:45.360 These are algorithms that have been used by every animal.

01:24:48.840 Think about the animal that's foraging for food.

01:24:50.800 They go down one path.

01:24:51.940 They're surprised they find food.

01:24:53.160 They go down another path.

01:24:54.140 They're sure they're on ascent.

01:24:55.680 They are sure.

01:24:56.440 And then they get nothing.

01:24:58.140 Well, what happens?

01:24:59.340 They learn to remember.

01:25:02.060 They automatically remember everything that led to that failure.

01:25:04.800 And people are very good at remembering that.

01:25:06.460 But be good at remembering the things that led to successes.

01:25:09.260 And then ride those neurochemical waves to the next node of exploration.

01:25:14.060 You're talking about exploration versus anxiety.

01:25:15.860 You can also do this with people in your environment.

01:25:18.540 You know, this is something B.F. Skinner pointed out when he was training animals.

01:25:22.340 He said, you can use threat and punishment to train animals.

01:25:27.000 But he said, the most effective mode of training isn't that at all.

01:25:30.180 You use sustained attention and reward.

01:25:33.560 And so imagine that you're training a rat to climb up a ladder rung by rung and then do

01:25:38.820 a little dance on the top and then climb down the other side.

01:25:41.220 So what Skinner would do, his animals were hungry, by the way.

01:25:44.960 They were starved to 75% of their body weight.

01:25:47.180 So they were pretty dopaminergically motivated by the provision of any food.

01:25:52.480 He would watch them wander around in the cage where a ladder was, let's say.

01:25:56.800 A little rat monkey bar apparatus.

01:25:59.640 And then when the rat would get near the ladder, he'd give it a food pallet.

01:26:02.360 And so then it was soon spending a lot of time near the ladder.

01:26:04.620 And now and then, while it was monkeying about, it would put one foot on the one paw on the

01:26:09.520 first rung.

01:26:10.140 It was like food pallet.

01:26:11.320 And then it would soon be doing that.

01:26:12.740 And then sooner or later, it would put the next paw on and he'd reward it.

01:26:16.020 And so Skinner trained pigeons to pilot guided missiles by pecking on photos in relationship

01:26:24.560 to the ground they were watching.

01:26:26.680 Right.

01:26:27.120 So he could use reward in an unbelievable.

01:26:29.020 So one of the things you can do in your local environment and with yourself as well is

01:26:32.780 you can watch people around you and you can see when they make small steps towards manifesting

01:26:39.380 some behaviors you'd like to see a lot more of.

01:26:41.880 And then you can tell them in this very differentiated, discriminatory manner.

01:26:46.900 You can say, hey, look, here's the sequence of actions you just undertook.

01:26:52.260 I saw that.

01:26:53.740 I noted the process.

01:26:55.360 And here's the delightful outcome.

01:26:57.340 Good work.

01:26:58.000 And man, if you do that repeatedly to people around you, and you don't want to do this

01:27:02.800 in a fake or manipulative way, but if you're attentive to what people are doing that's

01:27:06.920 good and you mark that with a reward, man, you produce behavioral transformations at a

01:27:11.560 rate that's just beyond belief.

01:27:13.120 I love it.

01:27:13.460 And everyone feels great about it too.

01:27:15.080 Yeah.

01:27:15.240 It's really a good habit, man.

01:27:17.320 It's giving credit.

01:27:18.240 That's separating the wheat from the chaff in the truest sense, to give credit where

01:27:22.540 credit is due.

01:27:23.760 Yeah, the behavior.

01:27:24.800 And you can imagine you're facilitating growth in the manner that you just described.

01:27:28.920 And maybe what neurologic or genetic transformation.

01:27:31.480 We didn't get to the gene expression part yet.

01:27:34.220 Yeah, the behaviorists like Skinner were truly brilliant.

01:27:38.380 And I think one experiment that I think is worth mentioning, which is kind of speaks to

01:27:42.800 the power of dopamine and why it's so vital to tap into these systems, even through menial

01:27:48.400 tasks, and then to build on their self-amplifying mode so that you can take on bigger things

01:27:53.340 in life, so to speak, positive goals, is there's a classic experiment now that's been

01:27:58.660 done in humans and in animals where you take two rats, separate cages, or you could do this

01:28:04.120 with humans where they're naturalistic conditions, where one of the rats or humans actually has

01:28:07.800 their dopamine depleted.

01:28:09.480 In humans, this happens through Parkinsonian things or the ingestion of drugs,

01:28:12.620 which accidentally deplete the dopaminergic neurons.

01:28:15.600 And what you find is that if you give them an opportunity to experience something

01:28:19.180 pleasurable, like hit a lever and get a pellet of food or people to access some very tasty

01:28:25.260 food, both people with dopamine and with very depleted dopamine, animals with dopamine or

01:28:31.320 without dopamine will eat the food.

01:28:34.300 They will pursue the food, but only if it's right in front of them.

01:28:37.940 If you put any kind of task between a person or an animal and a reward, what you find is

01:28:44.320 that a rat won't move one rat's length to press a lever to get the food.

01:28:49.580 So they are able to experience pleasure, but what they are unable to do is to embark on any

01:28:55.500 kind of effort to achieve that pleasure.

01:28:57.940 Right.

01:28:58.180 So that's so, oh, that's so cool.

01:28:59.640 So that means that in part what the dopamine system is doing.

01:29:02.840 So imagine that the purpose of the dopamine system is to elicit a satiating reward.

01:29:08.460 That's right.

01:29:09.000 Fundamentally.

01:29:09.860 But then the satiating reward is something that has to be approached in steps.

01:29:14.560 That's right.

01:29:15.120 And so in order to maintain the motivation necessary to approach the satiating reward,

01:29:19.900 you have to mark each of the steps with a marker of pleasure.

01:29:23.760 And so the dopamine system is marking the intermediary steps.

01:29:26.920 And then it's doing that to overcome the reluctance that you'd have to expend the energy in that

01:29:33.760 micro routine that would otherwise be costly by calculating the fact that there's a net reward

01:29:39.140 that's nested in the ultimate satiation.

01:29:42.140 That's right.

01:29:42.480 And parsing that out across the, yeah, yeah.

01:29:44.260 And sometimes people will experience tremendous anxiety in pursuit of their rewards.

01:29:48.780 You know, the social situation or the goal or the book, you know, people imagine failure

01:29:53.020 like crazy as I'm sure, you know, we've all heard and seen.

01:29:56.100 And what's critical, again, is this cognitive appraisal, this interpretation of that.

01:30:01.880 If you think of that anxiety as a natural system of getting you to move, of just biasing your

01:30:07.360 body toward movement, toward action, as opposed to inaction, because that's what anxiety really

01:30:12.020 is.

01:30:12.500 It's a bias toward action.

01:30:14.760 Then you can literally reshape the whole notion of what it feels like to have elevated heart

01:30:19.960 rate, maybe trembling hands, maybe flushing of the face when one is doing public speaking.

01:30:23.620 You do it enough times, you get pretty comfortable.

01:30:26.900 Now, there are situations in life I should just mention, such as sleep deprivation or

01:30:31.820 in particular, that tend to make this whole set of systems with prefrontal cortex and limbic

01:30:38.260 stuff and ACC and insula kind of dysregulated.

01:30:41.560 It makes it harder to manage.

01:30:42.980 That goes without saying, right?

01:30:44.340 You know, the quickest way to peel somebody apart is to sleep deprive them for two or three

01:30:47.660 nights.

01:30:48.100 One night, you're probably fine.

01:30:49.160 Right, right.

01:30:49.600 So, you know, all the basics of self-care, of good nutrition, social connections, sleep,

01:30:54.880 exercise, sunlight, those still apply.

01:30:57.740 I just want to mention that.

01:30:59.180 I want to make sure I answer your question about gene expression and permanent changes,

01:31:03.080 because I've failed to do that thus far.

01:31:05.380 One of the things that is absolutely key about the dopamine system is that it has a fast

01:31:11.700 component.

01:31:12.340 Dopamine is released, more adrenaline, aka epinephrine, can be released, and you can, you know, this

01:31:17.020 sort of upward spiral of energy and sort of success with the occasional drops, right?

01:31:21.440 I mean, nobody succeeds in every task, right?

01:31:23.560 Sometimes the phone rings or the doorbell rings and you fail, you know, goodness, you

01:31:28.280 fail to clean the cup.

01:31:29.520 You come home, like, are you going to crash into a puddle of tears?

01:31:31.780 No, you just clean it then and then put it away, right?

01:31:35.020 Of course.

01:31:36.220 But there's a slow system associated with achieving wins, even small wins.

01:31:42.480 And that slow system is in the form of hormonal control that then translates to gene control.

01:31:47.400 So two hormones in particular, testosterone and estrogen, which are present in both men and

01:31:52.740 women, males and females, of course, but to varying degrees, are both secreted when 0.98

01:32:01.580 the dopamine system is activated.

01:32:03.300 This has to do with the relationship between dopaminergic neurons and the pituitary gland,

01:32:07.640 which releases gonadotropins and luteinizing hormones, which then stimulate the testes and 0.77

01:32:12.480 the ovaries, et cetera, to release the so-called sex steroid hormones. 0.99

01:32:16.460 The sex steroid hormones, testosterone and estrogen, of course, are involved in reproductive

01:32:20.440 biology, but they are both vitally important, provided they are in the proper ratios, for motivational

01:32:26.860 biology, and for the following reason.

01:32:28.820 The steroid hormones are so-called lipophilic, and they can cross from the outside of a cell

01:32:34.600 through the cell membrane to actually into the nucleus of a cell and control gene expression.

01:32:40.580 So when we achieve wins repeatedly, and again, this doesn't matter if you're male or female,

01:32:45.640 you achieve wins repeatedly.

01:32:47.180 Testosterone is the molecule that eventually accesses not just cells to control their immediate

01:32:52.920 physiology, but goes into the nucleus of those cells and controls their gene expression.

01:32:59.220 And what it translates-

01:33:00.240 So does that mean, okay, so does that mean that demotivated men are producing less testosterone?

01:33:05.980 We can say that the data show that repeated failures take testosterone levels lower than

01:33:14.340 they would be otherwise.

01:33:15.820 That is not to say that people with low testosterone will always fail.

01:33:19.980 Those with higher testosterone-

01:33:21.080 No, no, no, no, no, no, no, no.

01:33:22.000 But just to be clear, because you are correct, but just people sometimes get hitched on this

01:33:26.920 causal part.

01:33:28.080 But indeed, one of the quickest ways to boost someone's testosterone is to have them achieve

01:33:35.080 a win of some sort.

01:33:36.760 Now, the win is translated-

01:33:38.060 Well, one of the things you do, one of the things you do in behavior therapy constantly

01:33:41.660 is you help people calibrate the zone of proximal development.

01:33:47.160 So imagine that that's Vygotsky's term, right?

01:33:49.680 And so if you're in the zone of proximal development, you're pushing your skill development one increment

01:33:55.400 forward.

01:33:56.460 And it's one that you can actually manage.

01:33:58.440 And so if you see people who are entirely stymied, we're sort of back to the cup of

01:34:02.000 coffee or the coffee cup example.

01:34:03.960 You want to find something they can do locally this week that would constitute at least a micro 0.98

01:34:09.640 win.

01:34:09.960 And if you talk to someone, you say, well, why don't you try cleaning up your room?

01:34:16.160 Because it's a complete catastrophic nightmare.

01:34:18.020 It's a good place to start.

01:34:19.400 This is often the case with people who are really demoralized and whose life is utterly

01:34:22.800 chaotic.

01:34:23.780 And maybe they come back later and say, well, you know, I had one client.

01:34:27.360 He just had a child, eh?

01:34:30.220 And he didn't want to mess up this child, but he was living at home.

01:34:32.640 He was like 35 years old. 0.93

01:34:34.200 He had a child out of wedlock by accident, but he didn't want to be a useless father.

01:34:37.740 And he was very afraid he was going to be. 0.89

01:34:39.520 And he had good reason to.

01:34:40.660 Like, he still lived at home.

01:34:42.160 He lived in his high school bedroom.

01:34:43.720 And it was a complete bloody mess.

01:34:45.740 He was living like a 12-year-old, you know, a bad 12-year-old.

01:34:48.720 And so I said, well, when was the last time that your carpet was vacuumed?

01:34:53.120 And he said, well, sometimes my mother does it, but it's probably been months.

01:34:55.740 I said, well, why don't you just bring the vacuum cleaner into the room and just vacuum 1.00

01:35:00.760 your carpet?

01:35:01.360 That'll be your task for this week, you know?

01:35:03.500 And I knew that was a bigger task than you might think, because he'd been in that room

01:35:07.920 for like 18 years, and it was a mess.

01:35:10.420 And so cleaning it up at all was a big deal.

01:35:13.000 He told me that he dragged that bloody vacuum cleaner into the doorway and left it 45 degrees

01:35:20.440 across the doorway and then stepped over it for the whole week without actually using it.

01:35:24.900 Oh, my goodness.

01:35:25.300 Yeah, resistance, say, from that was resistance from a psychoanalytic perspective, because

01:35:29.920 he saw the monster and was paralyzed.

01:35:33.980 And so what we did was we reduced the task.

01:35:36.020 I said, look, you've got some drawers in your bureau.

01:35:39.220 They're probably a mess.

01:35:40.160 Do you have a sock drawer?

01:35:41.040 Yes.

01:35:41.380 It says, like, clean up one half of the sock drawer this week.

01:35:45.100 That's it.

01:35:45.540 Just organize it.

01:35:47.160 So you just keep cutting the tasks down week by week until you find the threshold for positive

01:35:52.380 movement forward.

01:35:53.100 And then what's cool about that, too, is there's a Pareto principle issue associated with it.

01:35:58.360 So if you can find out where the person can start, it isn't linear progress.

01:36:02.880 It's exponential progress forward.

01:36:05.000 And so even if they have to start at a micro level, it doesn't really matter because they

01:36:08.880 get much better at it very, very rapidly as they accrue successes.

01:36:12.560 Maybe that's because they're learning in the way that you described.

01:36:15.980 Okay, so back to the gene regulation.

01:36:17.580 It increases testosterone, the wins.

01:36:19.420 Yeah, so testosterone are associated wins.

01:36:21.780 Winners tend to be able to win more.

01:36:23.660 There's some, et cetera.

01:36:25.120 But, you know, if we want to bring this into the common world, you know, a few years back

01:36:29.920 when I started doing some public-facing education, I started getting a lot of questions, especially

01:36:34.640 on YouTube, from young males about pornography and masturbation.

01:36:41.920 And this becomes very relevant here.

01:36:43.840 We have to remember that this dopaminergic system is generalizable to many different behaviors,

01:36:49.900 right?

01:36:50.140 Academic pursuits, sports pursuits, relationship pursuits.

01:36:53.060 But fundamentally, it was, again, I wasn't consulted the design phase, but fundamentally,

01:36:58.700 it's tacked into the adaptive survival behaviors.

01:37:01.800 And every species, including ours, has at least two major motivations, which is to protect

01:37:07.560 its young and to make more of itself, to make more young at some level.

01:37:11.620 People can opt out of that.

01:37:12.920 But one of the absolutely pathologic situations for any animal or human is to be able to access

01:37:20.080 repeated dopamine surges without effort or any pursuit that's self-directed or that's

01:37:27.300 directed, I should say.

01:37:28.560 So, for instance, cocaine, a drug which potently increases dopamine or methamphetamine, which

01:37:34.360 potently increases methamphetamine, but doesn't require any sort of adaptive action pursuit except

01:37:40.760 to acquire the drug and spend money on it.

01:37:42.640 No sacrifice.

01:37:43.120 No sacrifice.

01:37:44.020 So, essentially, what ends up happening is the circuit that gets rewarded is only the drug-seeking

01:37:49.620 behavior, and no other behavior will give the kind of potent dopamine release that cocaine

01:37:55.520 or methamphetamine will, which is why they are so pernicious.

01:37:58.920 Now, likewise, I'm not...

01:38:00.780 Well, plus they have that powerful reinforcing effect, right?

01:38:04.220 So, not only do you get that kick, but what's reinforced by the dopamine release is the behaviors

01:38:10.520 that were right prior, particularly right prior to the ingestion.

01:38:14.740 And if all that is is the drug-taking behavior, that's all that develops.

01:38:17.900 That's right.

01:38:18.260 You build that monster inside your head. 0.99

01:38:20.080 That's right. 0.95

01:38:20.480 So, I can see where you're going on the pornography phase.

01:38:22.460 Right.

01:38:22.720 So, I was starting to get a lot of questions.

01:38:24.400 I was kind of surprised.

01:38:25.380 I thought, well, you know, I'm male, and, you know, maybe that's why they feel comfortable

01:38:28.180 asking.

01:38:28.600 But people were saying that we're asking about pornography, and they were asking, you know,

01:38:32.260 I realize we want to, you know, I'll just be direct about it. 0.84

01:38:35.740 They were asking whether or not masturbation was bad. 0.99

01:38:38.500 They were asking whether or not masturbation with ejaculation was particularly bad. 0.98

01:38:42.920 And here's my stance on this. 0.97

01:38:43.980 I'm a biologist and a neuroscientist, not a psychologist.

01:38:46.460 But what we know for sure is that if an individual repeatedly engages in this circuitry, let's

01:38:53.600 say masturbation and pornography with increasingly potent forms of stimulation that are on a screen,

01:39:00.980 a couple of things happen.

01:39:02.000 First of all, what's being reinforced?

01:39:03.940 What's being reinforced is a high dopaminergic response to watching other people engage in

01:39:09.440 sexual behavior, which is very different than being in a first-person sexual experience,

01:39:14.340 okay?

01:39:14.980 So right there, you know that what's being reinforced is not actually any kind of improvement

01:39:20.120 in communication skills.

01:39:21.980 It's voyeurism.

01:39:22.260 It's voyeurism.

01:39:23.660 And as these questions started to come in more and more, I started to realize there was a lot

01:39:27.760 of kind of undertones of people talking about fear of or experience with sexual dysfunction

01:39:31.920 that clearly pornography can lead to.

01:39:34.400 And here I'm specifically talking about males.

01:39:36.140 I actually don't know the literature on females. 0.99

01:39:38.180 So here I'm talking about-

01:39:40.120 Females don't use visual pornography to the same degree. 1.00

01:39:42.580 I see. 0.99

01:39:42.840 They use literary pornography.

01:39:44.340 I see.

01:39:45.200 So-

01:39:45.680 Yeah, yeah.

01:39:46.500 So, and then you start to think about, okay, what happens in the cascade or the arc of

01:39:50.380 sexual arousal and orgasm?

01:39:52.960 What happens is that initially there's a, it's parasympathetically dominant, meaning if somebody

01:39:58.000 is too stressed, they actually can't engage in sexual behavior.

01:40:01.640 The arousal response doesn't occur.

01:40:03.760 The erection is blunted.

01:40:04.600 But the actual orgasm response and ejaculation is strongly associated with the so-called sympathetic

01:40:10.680 nervous system, which has nothing to do with sympathy, has everything to do with, it's

01:40:13.720 a kind of a stress response.

01:40:15.340 And then it reverses to a parasympathetic response.

01:40:18.180 And a hormone called prolactin increases dramatically after ejaculation in males.

01:40:23.300 What does that do?

01:40:24.000 That blunts dopamine release and testosterone for a very long period of time, which makes

01:40:28.860 sense if pair bonding and sort of, you know, in our species anywhere, there's this idea

01:40:33.840 that then other molecules would be exchanged with partners, pair bonding, potential for

01:40:38.120 raising mates, et cetera.

01:40:39.720 Without getting into a huge discussion about that, the point is this.

01:40:42.840 Masturbation and pornography are potently tapping into the dopamine system and can undermine

01:40:49.460 the very processes of what I consider healthy processes of finding a mate, you know, dating,

01:40:55.620 communication, eventually, if it's appropriate, sexual interaction, et cetera.

01:41:00.000 It's undermining pair bonding.

01:41:01.680 And pair bonding.

01:41:02.200 Okay.

01:41:02.700 So here's a question.

01:41:03.640 If you're seeking sexual release through pornography and you go through the whole cycle and you get

01:41:09.200 prolactin release, do you bond with yourself?

01:41:12.180 So this is very interesting.

01:41:14.000 The, um, it's the biology explains it as what's left there is a kind of an open loop, a kind

01:41:20.300 of an emptiness, right?

01:41:21.700 Because bonding with the self is a, is a complicated notion.

01:41:24.960 I mean, it had, there's a healthy version of that, of course, loving oneself and, um, and

01:41:29.200 self-referencing.

01:41:30.160 And again, this is more, uh, your, uh, far more your domain than mine in terms of what a

01:41:34.680 healthy self-relation is, but in the absence of, uh, a real partner there of a absence of

01:41:41.220 real sexual partner, there's an open loop of neurochemicals, including oxytocin and prolactin,

01:41:46.100 the dopamine, remember dopamine goes up during pursuit anticipation, then peaks and then crashes

01:41:52.260 below baseline after orgasm and ejaculation.

01:41:56.100 So this kind of low that people fear is putting them into an a motivated state.

01:42:00.260 We can think of this.

01:42:01.300 If I were to kind of expand on, it would be, it's this, it's this kind of a neurochemical

01:42:05.440 psychological equivalent of making your home environment filthy for a while, not actually

01:42:11.260 putting you into this positive amplification of dopamine.

01:42:14.360 So it depletes the dopamine system and it's likewise in drugs of abuse and addiction.

01:42:19.380 It eventually depletes the dopamine system.

01:42:21.600 Initially, there's a huge dopamine surge with drugs of abuse like methamphetamine and cocaine,

01:42:25.840 but over time people are using more and more to achieve what is not such a great high.

01:42:30.660 You even see this a little bit with kind of consumption of energy drinks, like people

01:42:36.980 are taking more and more chemicals within their energy drinks and they're thinking about

01:42:40.440 loud, fast music, energy drinks, it's kind of stacking of dopaminergic tools.

01:42:45.240 Now that's not as pathologic.

01:42:46.680 In fact, I'm, I'm, there are some energy drinks I'll occasionally drink and I enjoy them.

01:42:50.800 I don't think we need to be entirely afraid of, of pursuing or engaging in things that release

01:42:56.080 dopamine, obviously healthy sexual behavior, food that we love, social engagement, all

01:43:01.080 of these things can be dopaminergic.

01:43:02.960 It's the big peaks in dopamine that are not associated with any prior effort or organization

01:43:08.480 of self that are particularly dangerous for the human being.

01:43:12.400 Yeah.

01:43:12.540 Well, you could see that, that you could see that, that that's a cardinal danger of, of

01:43:16.880 affluence then.

01:43:18.580 That's right.

01:43:18.940 This is why the children of, you know, you know, that's right.

01:43:21.420 You know, you cannot get rats addicted to cocaine if they live in their natural environments.

01:43:25.620 Is that right?

01:43:26.920 You can only get rats addicted to cocaine if they're isolated rats in a cage.

01:43:32.180 Yeah.

01:43:32.640 They won't bar press for cocaine in the natural environment.

01:43:35.100 And it's because they have alternative sources of dopaminergic gratification.

01:43:39.000 Very interesting.

01:43:39.780 So yeah, it's very interesting.

01:43:41.740 Yeah.

01:43:41.760 The children of very wealthy people who are overindulged.

01:43:45.240 I've seen that many times, many, many times, and it is a very sad sight.

01:43:49.860 Um, yeah, well, they're not optimally deprived, eh?

01:43:53.240 And that, that issue of optimal deprivation, that's, that's a killer issue for an affluent

01:43:57.360 society.

01:43:58.220 We're going to have to stop because it's been more than an hour and a half.

01:44:03.540 And I don't want to stop because there were a bunch of things I wanted to talk to you about.

01:44:06.860 I wanted to talk to you about, and I should let everybody know who's listening.

01:44:10.000 If you go to Dr. Huberman's podcast, you can hear him discuss some of these things.

01:44:14.700 We were going to talk about dreams, sleep, rest, and learning, because we didn't talk

01:44:19.320 about the relationship between dreams and learning and reinforcement, which I'd love

01:44:23.060 to talk to you about.

01:44:24.200 We didn't talk about fasting.

01:44:26.500 We didn't talk about physical health, aging, and how to ameliorate it.

01:44:30.240 We didn't talk about salt.

01:44:32.480 We didn't talk about flexibility, and we didn't talk about gratitude.

01:44:35.700 So I would say we should probably do another podcast at some point.

01:44:39.120 I would also tell everyone who's watching and listening that Dr. Huberman invited me onto

01:44:43.540 his podcast.

01:44:44.200 And so some of these things we can discuss when that happens, because I would like to

01:44:47.820 have that happen.

01:44:48.760 I look forward to that.

01:44:49.900 And I would also like to, yeah, it'd be good.

01:44:51.880 It'd be good.

01:44:52.380 We obviously have lots to talk about.

01:44:54.200 I would also tell people, I'm going to do another half an hour with Dr. Huberman on the

01:44:58.580 Daily Wire Plus platform.

01:44:59.880 I use that time to investigate a little bit people's success stories, I suppose.

01:45:06.500 I think it's very useful for young people in particular to get exposed to individuals who've carved

01:45:13.620 out success, at least in some domains of their life, and to find out what the story pathways

01:45:18.660 are, let's say, the autobiographical pathways that facilitate that kind of success.

01:45:23.780 Hello, everyone.

01:45:24.600 I would encourage you to continue listening to my conversation with my guest on dailywireplus.com.

The Jordan B. Peterson Podcast - October 13, 2022

296. Neuroscience Meets Psychology ｜ Dr. Andrew Huberman

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