How to Optimize Cognitive Function & Brain Health | Dr. Mark D'Esposito

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Welcome to the Huberman Lab podcast, where we discuss science
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and science.
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Based tools for everyday life.
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I'm Andrew Huberman, and I'm a professor of neurobiology and
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Ophthalmology at Stanford School of Medicine. My guest today is
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doctor and Professor Mark Esposito. Doctor Mark Esposito is a
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neurologist and a professor of neuroscience and psychology at the
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University of California, Berkeley.
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He is a world.
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Expert in the brain mechanisms controlling executive function and memory.
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Executive function is the way in which we are able
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to designate and carry out specific cognitive strategies, and it
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is fundamental to every aspect of our daily lives. And
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because so much of being effective in daily life involves
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using specific context relevant batches of information in order to
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understand what to do and when, and what not to
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do and when, and to come up with strategies that
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are very adaptive for us to move forward in the
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context of relationships, work, school, and athletics and on and on.
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There's really no separation between executive function and memory. And
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today doctor Desposito explains the neural circuits controlling executive function
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and memory. How They interact the key role of dopamine
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in executive function and something called working memory, and teaches
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us ways to optimize executive function and memory, that is,
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how to optimize cognitive function. In addition to discussing how
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to optimize cognitive function in the healthy brain, today's discussion
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also centers around how to restore cognitive function in disease
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or injury. Conditions that deplete executive function and memory, such
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as traumatic brain injury, concussion, Alzheimer's, Parkinson's, and attention deficit disorders.
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Doctor Desposito shares with us research findings both about behavioral
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and pharmacologic strategies to enhance executive function and memory. By
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the end of today's discussion, you will have learned from
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doctor Desposito a tremendous amount about the modern understanding of cognition,
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that is, thinking and memory and the carrying out of
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specific cognitive strategies. You will also learn a tremendous amount
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about how to optimize brain function and brain health. Before
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we begin, I'd like to emphasize that this podcast is
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separate from my teaching and research roles at Stanford. It is, however,
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part of my desire and effort to bring zero cost
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to consumer information about science and science related tools to
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the general public. In keeping with that theme, I'd like
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to thank the sponsors of today's podcast and now for
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my discussion with doctor Mark Desposito. Doctor Disposito, welcome, Andrew.
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Thank you so much for inviting me. I'm really looking
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forward to our conversation.
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You may not remember me, but I remember you when
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I was a first year graduate student and you showed
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up at Berkeley, one of the first people to really
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bring functional imaging of the human brain to Berkeley, bring
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a neurology and a clinical emphasis to the neuroscience studies there,
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and it's really just blossomed, and it's been a real
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thrill for me to see all the magnificent work out
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of your laboratory over the years. I know you also
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still see patients. So the topics that are of interest
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to you, I know are of great interest to our audience.
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Maybe we just start off with a few of the
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basics and do a little functional neuroanatomy lesson for folks.
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Not to scare anyone, don't worry, this will be accessible
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to everyone, and just talk about the frontal lobes and
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prefrontal cortex and a little bit of what those structures do,
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because many times on this podcast I've said, Okay, the
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neural real estate right behind your forehead is involved in
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context and planning, etc. But you're the real expert here.
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How should we think about what the frontal lobes do
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and their various roles in health and disease.
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Yeah, so there's four lobes.
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There's a frontal lobs, parietal, temporal, eccipital, and the frontal
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lobes probably take up more do take up more territory
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than it is probably about a third of the cortex.
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And within the frontal lobes, I don't I'm going to
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use their frontal lobes probably in our conversation a lot,
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but what I really mean is the prefrontal cortex. So
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within the frontal lobes there's also areas that orn for
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motor function as well. But when we're talking about the
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frontal lobes and talking about it's you know, involvement higher
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level cognitibilities. We're talking about the prefrontal cortex, and this
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is what's considered sort of the highest level of cortex
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in the brain. And so yeah, when you think of
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when you think about it, people assign it all sorts
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of functions. Almost every function you think of people have
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sort of put into the frontal lows. But I think
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what we've all kind of uh moved towards is this
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idea of executive function, this ability, this ability to plan,
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to organize, to really transfer our thoughts, you know, into
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an action, and really to be guided by goals and
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intentions and not be kind of taken, you know, kind
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of ruled by sort of just automatic behaviors. And a
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word we use in cognitive science is called cognitive control.
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So cogntrol executive function is what we attribute to the
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frontal lobe. And so you can think of it as
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you know, the CEO of the brain, or the you know,
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or the conductor of the orchestra real the part of
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the brain that's that's really controlling the rest of the brain.
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So yeah, if you had to choose which part you
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wanted to not leave home, your front it's your frontal lobes.
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Speaking of which, what are some of the uh symptoms
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of mild frontal lobe damage and severe frontal lobe damage
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damage brought about either through NERD degenerative disease or physical injury.
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I know, we're going to talk a bit about both
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today or a lot about both. But how would lack
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of executive function show up maybe on kind of a
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subtle level.
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Yeah, I mean, at first I should say is that
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it shows up all the time because when when uh
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and and frontal lobe behavior is probably much more prevalent
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than we realize.
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Certainly we think about it.
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When you have a brain injury to the frontal lobes,
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and there's lots of neurological disorders like stroke and in
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tramatic brain injury and Alzheimer's these that can affect in
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frontal lobe. And there's a number of you know, psychiatric
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disorders subsessive compulsal disorder and schizophrenic and depression that are
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thought to be frontal lobe dysfunction. But when you're sleep
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deprived and when you're stressed and just normal aging, the
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frontal lobe seems to be the first system that's affected
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because it really is involved in the highest level. So
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when we're having a bad day, when we're having difficulties
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sort of setting priorities, when we're having difficulties achieving the
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goal that we've set out, when we get distracted, you know,
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when we get distracted, you know, when we're not able
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to sort of adapt and be flexible. These are all
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the type of things that are reflect that our frontal
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lobes are not functioning optimally.
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Approximately, what age does the frontal lobe circuitry come online?
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So to speak?
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I mean, when I see a baby. Babies can orient
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their eyes towards things, but they're rather reflexive in where
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they'll place their eyes. But by the time kids are
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three or four, they can certainly, you know, play with
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blocks or interact with other children or their parents. But
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it seems that, you know, full functionality the frontal lobes
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is really gradual. At least that's my non clinically trained assessment.
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You know.
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Yeah, I mean it's a really tough question to know
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when they're fully developed, because these studies haven't been done.
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When MRI was introduced and we're able to sort of
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image the brain in a non evasive way, then studies
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did start to come out trying to sort of map
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out at what age does your frontal lobes fully developed?
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And it seemed like it was early into your twenties.
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You know, I always say that it's not surprising that
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you can't rent a car into your twenty five that
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the insurance companies knew before neuse scientists did. As to
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when your frontal lobs have, you know, when your decision
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making skills at their highest, and so that's probably about
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right into your twenties, is probably.
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Before your front loves are fully developed.
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And it's really interesting question is why does it take
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so long. It's the area of the brain that takes
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the longest to develop, and why is that? And I
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think there's a reason. I think that this sort of
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slow developed the frontal loves allows us to explore, allows
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us to think about novel ways of solving problems, allows
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us to take in the world. If they were shut
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off earlier, it would lead to maybe a much more
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sort of rigid kind of you know, less flexible kind of.
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Behavior that we've seen things.
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So I think that it helps to be it take
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a long time to develop, but also it obviously leads
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to some problems sometimes in adolescence, as we see sometimes.
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Can one see a lack of frontal load maturity in
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just the sheer number of physical movements that a child makes. So,
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for instance, in a classroom of you know, let's say,
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you know, fourth graders. Oftentimes there'll be a range of
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a parent ability of kids to sit still or to listen.
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Do we think that the kid that's having a hard
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time focusing and listening to instructions or studying their body
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when they're told to sit still. I don't know if
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they still tell kids sit still, but they were telling
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me to sit still right when I was a kid.
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Is that somehow reflective of a you know, slightly lagging
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front frontal lobe function and maturity. Whereas that you know,
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the kids that can sit you know, still in stoic
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and focus, does that mean that they're a little bit
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more accelerated along that trajectory.
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Yeah, it's hard to say.
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I mean, the frontal lobe is is a big territory
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and we can get into it, but there's you know,
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the frontal lobe probably has twenty five different sub regions
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within it, and and so grossly we think about the
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frontal lobes as the latter portion of the frontal lobes,
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which is involved in these executive function probably supports these
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executive functionabilities. But then we've got another part of the
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frontal lobes called the orbital frontal cortex was probably evolved
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more in social and emotional behavior. So you know, when
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we think of again, when we think about front low behaviors,
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they kind of you have to break. There's so many
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different type of front low behaviors. So that type of
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behavior which may be evolved in being able to inhibit,
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you know, your motor movements or maybe not being distracted,
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may reflect that.
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That system is a little bit delayed.
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But it could be that another system, the one that's
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involved in planning and organizes, you know, is more developed.
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And I do think they develop at different trajectories.
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So with the frontal lobes essentially serving an executive or
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CEO type function, goal directed behavior, intentions, cognitive control. These
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are the terms you used. Where are the rules? What
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do the rules look like? You know, when I think
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about brain function, which I've spent a lot of my
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life thinking about, think about chemical and electrical signaling between neurons,
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different neurons communicating more or less at a given moment,
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reflecting some sort of circuit as we call it, and
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then some behavior or some decision comes out. And if I,
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for instance, I have to get my driver's license renewed soon,
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so if I go to the department of motor vehicles.
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What a lovely experience. That is the moment I get
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there that I sort of lock into a certain rule set.
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When I'm home, I'm in a different rule set. When
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I'm in with my friends versus when I'm with my parents,
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different rule sets. And it seems that the frontal lobe
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is really good at drawing on context based on knowledge
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of where one is, and then coming up with kind
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of algorithms that are appropriate or inappropriate to run in
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that context. But what is the nature of these algorithms?
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Are they of.
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The okay, shut down all cursing in this environment, Okay,
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you're free to just quote unquote be you, I mean
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when when it really comes down to it, it has
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some interesting philosophical aspects too, because just be yourself, be authentic,
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be vulnerable, you know, all these things make sense. But
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of course one needs to be appropriate with the context.
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So how does this work, Like, what is the what
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are the algorithms? How does this work?
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Right?
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Because because that's a pretty common example of our patients
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that they don't follow the rules they they you know,
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if you're sitting in someone's the doctor's office and the
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phone rings, you know, not to pick up his phone,
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but the patients don't and they may pick up the phone.
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There's this doctor Lamite who's a neurologist from France, published
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these beautiful papers in the eighties of all these things
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that patients did that just that broke the rules and
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so and we just kind of pulled to their environment
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without having any context to it. If he put a
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pair of glasses on the table and didn't ask him
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to put them on, they would put them on, even
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if they had a pair of glasses on already. Or
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he took them to their apartment and they saw the
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bed and they jump into the bed and go under
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the cover. So or he saw he had a nurse
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and she he put a blood pressure cuff there, and
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she picked up the blood pressure cuff and just start
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taking his blood pressure again, not asking him to do
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any of these things.
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And so they they they just don't follow sort of
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the social rules, but they're there. They haven't lost rules.
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If you ask these patients was that the appropriate thing
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to do, they'll say no, no, they know it's appropriate. Yeah,
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they say no, I'm not supposed to answer your phone.
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But wow, so they know better, but they can't control
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the empac exactly.
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So it's it's so it's not a breakdown at the
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rules disappear. It's that they can't apply the rule, that
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they can't apply the rules properly, and and and that's
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true for a lot of patients, even with kids. You know,
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you tell them, don't have anything to eat before dinner
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because we're having dinner, and then they're sitting there having
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a sandwich and you say, what did I just tell you?
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You said, well, don't eat, but I'm.
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Hungry, right.
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Another sort of example is sort of the frontal lobes
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not completely kind of developed. So when I think about rules,
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I think about the brain. You know, the brain processes information, obviously,
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but it also stores information. The most important thing it
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does is store all sorts of information all over the brain.
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And I think, what the frontal lobes do is they
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store rules. And what's interesting about the way it stores
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rules they seem to store the rules in a hierarchical fashion.
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And what I mean by that is that there's different
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levels to rules.
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I like to give the example.
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Of playing golf. I tell a story a lot about
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my good friend Bob Knight. When hits the ball into
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the you know, off into the woods and he has
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to try and hit the.
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Ball out of the woods.
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He's holding on to all different levels of rules on
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how to successfully get his ball back towards the green.
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So the most simplest one is just like where you know,
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where is the flat? You know, I've got to maintain
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the orientation to get to the flag, you know.
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So he's holding that.
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He also at a higher level rules he knows that
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if he kicks the ball it's a penalty, so he's
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not going to do that, right, And then another higher
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level rule might be if I just keep doing this,
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you know, this is going to be healthy for me.
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So he's storing all this information at sort of at
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different levels of hierarchy, and he's applying are applying it
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to ultimately achieve this very simple act, so simple act
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of hitting the off ball. So yeah, so I just
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I think about sort of the frontal cortex is able
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to call upon the rule in the appropriate context, and
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if you don't have your frontal loves, it doesn't get
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pulled up properly.
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And those rules must be learned right that There's no
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way I can imagine that one can be born into
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the world with these rules sets intact. I think about
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the two marshmallow experiment that's sort of famous now, where
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kids are offered to eat one marshmallow right away or
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differ and get two marshmallows.
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These adorable videos the.
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Kids, the various strategies they use, like turning away and
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poking the marshmallow. And you know, there's some debate ongoing
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as to whether or not success or lack of success
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in deferring to the two marshmallow reward is predictive of
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other things in life. But leaving that aside, am I
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correct and assuming that that task is a frontal lobe task?
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The kids are of a novel rule. You can have
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one marshmallow now, or wait patiently and then with and
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overcome the craving for that one marshmallow, and then you'll
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get two. And presumably that that experiment is engaging the
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frontal lobes. And you know, we can only speculate, but
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some kids are able to defer, some are not. And
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I can imagine that at that age there's a lot
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of neuroplasticity strengthening and weakening of connections in the brain
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in an experience dependent way.
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So does that mean that.
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Children and perhaps adults as well can train up their
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prefrontal cortical abilities to strategize and defer in a way
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that's adaptive.
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Absolutely, I mean definitely, you can learn strategies to not
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only sort of learn rules, but how to apply goals
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when when you start to think about that task in particularly,
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some of it has to do with sort of maintaining
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a goal and maintaining a goal of different You know,
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time scals, right, and children tend to sort of act
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on goals that are much more short on a shorter
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time scale. You know, I'm going to have the sandwich
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right now because I'm hungry, as opposed to wait till
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till dinner, which is a longer, longer term goal. And
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so yeah, this default is sort of the shorter you
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can you can learn that maintaining a longer type goal
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can be much more beneficial than the short term goal,
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even though it doesn't seem obvious.
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And we all learned that right as we as we
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get oloser to us, we.
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Keep our eye on the ball sort of more long
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term goals, and that's very predictive of how successful we
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can we can be the farther out we can maintain
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a goal, and that's what the That's what the prefrontal
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cortex does. It maintains goals and then applies those goals.
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And if you don't apply them, then you lose, you know,
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then you then all of this executive function breaks down.
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Do you think that these algorithms and rules that the
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prefrontal cortical circuitry can learn and indeed does learn, can generalize. So,
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for instance, when my first year of college was this
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disaster for reasons that are interesting right now, but then
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when I came back my sophomore year, really spring of
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my freshman year, it was like, okay, it's on. It
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was I had to rescue myself. And so one of
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the things I used to do was I would study
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and I would set a timer so I refuse to
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get up, even if I had to use the restroom
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very very badly. I would set up all sorts of
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behavioral constraints, and I like to think that I was
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building up my prefrontal ability to refocus on the material.
359
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And fortunately for me, there were no smartphones back then.
360
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It was much easier Internet now we had email, but
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no no real internet browsing to speak of. And I
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like to think that the I sometimes call it and
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This is terrible to call it this because it's not
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nearly exhaustive of the underlying function. But I call it
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sort of like limbic friction. It's like, there's this friction
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that one feels mentally, like you want to get up,
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you want to use the restroom, you want to eat something,
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you want to call a friend, but you stay focused
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on the task at hand. Do you think that that
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business of quote unquote staying focused on the task at
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hand can generalize because of the sensations it generates in
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the body and then you know, oh, yeah, this is familiar.
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This is just like studying, but in a different context
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one stays focused. Or do you think that the prefrontal
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cortex is so context specific that it needs to learn
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the rules for every individual situation. And then this has
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all sorts of implications for behavioral restraint and focus and
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attention deficit. So if you could just speculate, I know
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a number of people are interested in how they can
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be more focused, and people often defer to like what supplement,
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what drug? Okay, those are interesting conversations, but I think
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ultimately we're talking about neural circuitry.
383
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Yeah, I mean, it absolutely can generalize that that's been
384
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a frustrating thing into trying to develop what we call
385
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cognitive therapy, where we teach we try to improve someone's
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memoryability or we try and improve someone's executive functionability. The
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00:19:54.359 --> 00:19:57.440
disappointing early results was always that, yeah, they get very
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good at the task that you've trained them at, doesn't
389
00:20:00.279 --> 00:20:02.680
seem to generalize anything else. So if you teach them
390
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a you know, a task, they can do amazing things
391
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like match a finger to a color or a shape
392
00:20:08.079 --> 00:20:11.000
and put together all sorts of rules and then and
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they're really good at that task very quickly. And then
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00:20:13.720 --> 00:20:16.319
nothing's really changed in their real life. But I think
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00:20:16.400 --> 00:20:18.559
we've learned on how to sort of and how to
396
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try and make it translate to real life. And so,
397
00:20:22.720 --> 00:20:26.519
for example, there's there's a therapy called goal management training
398
00:20:26.559 --> 00:20:29.839
which is developed by Brian Levine and colleagues at the
399
00:20:29.920 --> 00:20:33.279
Rotman Research Institute of Toronto, where they've been very successful
400
00:20:34.039 --> 00:20:40.119
in teaching patients how to approve your executive function and
401
00:20:40.160 --> 00:20:42.759
how to make that translate into real world. But it's
402
00:20:42.920 --> 00:20:46.599
very hard work, it's it's very therapists driven, it requires
403
00:20:47.319 --> 00:20:51.519
it requires a series of trainings. For example, people learn
404
00:20:52.079 --> 00:20:55.319
they develop individual projects like planning a meal, or planning
405
00:20:55.400 --> 00:20:58.720
a family vacation, or planning a podcast, and then they
406
00:20:58.759 --> 00:21:02.440
work through what's involved in that sort of very specific project,
407
00:21:02.480 --> 00:21:05.200
how you how you stay focused, how you don't just
408
00:21:05.319 --> 00:21:07.799
get distracted, how you keep your eye on the ball,
409
00:21:07.880 --> 00:21:12.079
how you break it down to sub goals, how you
410
00:21:12.079 --> 00:21:15.119
you monitor what you're doing, how you don't let anxiety
411
00:21:15.160 --> 00:21:17.599
and procrastination get involve. But it's a it's a very
412
00:21:17.640 --> 00:21:20.400
active sort of process. But when you add all that
413
00:21:20.559 --> 00:21:24.119
to it in a very discipline way over the course
414
00:21:24.160 --> 00:21:27.079
of many hours and many weeks, it does translate patients
415
00:21:27.119 --> 00:21:30.680
and individuals to say, yeah, I'm just better at doing things.
416
00:21:30.759 --> 00:21:32.440
I mean, the whole goal is to do things right,
417
00:21:32.480 --> 00:21:34.519
and I'm just better at it. I don't know what
418
00:21:34.599 --> 00:21:36.880
it is, but I'm not just better at what you
419
00:21:36.960 --> 00:21:37.240
taught me.
420
00:21:37.279 --> 00:21:38.720
I'm just better at other things.
421
00:21:38.759 --> 00:21:40.720
So I do have a lot of hope that these
422
00:21:40.839 --> 00:21:43.720
kind of therapies will generalize to the you know, to
423
00:21:43.799 --> 00:21:46.359
people's real life throughout.
424
00:21:46.400 --> 00:21:50.960
The term limbic friction again not a technical or clinical
425
00:21:51.279 --> 00:21:53.720
or official term in any way, but just a way
426
00:21:53.759 --> 00:21:57.759
to kind of capture some of the interactions of the
427
00:21:57.759 --> 00:22:00.559
frontal cortex with other circuitry. I mean, there's far more
428
00:22:01.960 --> 00:22:06.240
involved in agitation and challenges focusing than the limbic system,
429
00:22:06.279 --> 00:22:12.279
but it certainly is involved. When thinking about the frontal cortex,
430
00:22:12.319 --> 00:22:15.440
I often think about it's connections with other areas of
431
00:22:15.480 --> 00:22:17.079
the brain. So maybe we could talk a little bit
432
00:22:17.119 --> 00:22:21.480
about those connections, and in particular the connections from the
433
00:22:21.519 --> 00:22:28.240
frontal cortex to let's call it circuitry that controls reflexive behaviors.
434
00:22:28.559 --> 00:22:32.039
What is the nature of that circuitry and can we
435
00:22:32.039 --> 00:22:35.160
make any general statements like does the frontal cortex really
436
00:22:35.200 --> 00:22:41.960
serve to provide a quieting suppressive function on reflexes or
437
00:22:42.039 --> 00:22:44.839
is it more of an orchestra conductor where it's saying, okay,
438
00:22:44.880 --> 00:22:46.319
a little bit of that and a little bit of that,
439
00:22:47.119 --> 00:22:50.400
and then what comes out in behavior or speech is
440
00:22:50.440 --> 00:22:55.000
something that looks very organized, but is actually the reflection
441
00:22:55.079 --> 00:22:56.559
of a lot of selective filtering.
442
00:22:57.839 --> 00:23:00.759
Yes, I mean the prefrontal cortex. What's so fascinating about
443
00:23:00.880 --> 00:23:03.279
is that I would say it connects to every part
444
00:23:03.279 --> 00:23:07.680
of the brain, cortex and the subcortex, and almost every
445
00:23:07.720 --> 00:23:10.279
part of the brain connects to it, so that I
446
00:23:10.319 --> 00:23:13.839
mean that right there tells you it's a pretty important area,
447
00:23:13.839 --> 00:23:15.400
and it has to if it's going to be in
448
00:23:15.440 --> 00:23:19.920
this CEO, you know, conductor type experience role, and so
449
00:23:20.240 --> 00:23:23.680
it's in this privileged position just anatomically, so that that
450
00:23:23.720 --> 00:23:26.000
gives us great insight to how important it is. And
451
00:23:26.039 --> 00:23:28.079
so it is connecting, and then of course we could
452
00:23:28.119 --> 00:23:31.319
talk about it how it's connected to the body as well,
453
00:23:31.359 --> 00:23:33.759
how it controls heart rate and respirations as well. So
454
00:23:33.759 --> 00:23:37.480
it's not just this the brain. So but it's really interesting,
455
00:23:37.759 --> 00:23:40.799
like you said, is it really just sort of maintaining
456
00:23:41.279 --> 00:23:43.559
telling you what's relevant and what's not relevant, or is
457
00:23:43.559 --> 00:23:45.680
it allowing you to switch? I think it does all
458
00:23:45.720 --> 00:23:48.599
those things. It definitely what we call sends these top
459
00:23:48.640 --> 00:23:52.319
down signals. It's sending signals to other brain about what
460
00:23:52.359 --> 00:23:54.599
you should be paying attention to and what you shouldn't
461
00:23:54.599 --> 00:23:58.200
be paying attention to. So, for example, if we've done
462
00:23:58.240 --> 00:24:01.039
studies with functional imaging where we have them look at
463
00:24:01.079 --> 00:24:04.319
pictures of faces and scenes, and that lights up the
464
00:24:04.359 --> 00:24:06.599
back of your brain. Your visual cortex has areas that
465
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are can process faces and process scenes, and but sometimes
466
00:24:11.640 --> 00:24:13.680
we have you just want to pay attention to the
467
00:24:13.720 --> 00:24:16.119
faces and not the scenes and other times we want
468
00:24:16.160 --> 00:24:18.519
you to pay attention to the scenes and not the faces. Well,
469
00:24:19.200 --> 00:24:21.799
you know, even though it's getting the same bottom up
470
00:24:22.279 --> 00:24:27.000
visual input, the prefrontal cortex will show greater activity to
471
00:24:27.079 --> 00:24:30.559
the relevant information. It'll it'll it'll sort of it's sending
472
00:24:30.599 --> 00:24:35.160
a signal say, pay attention to the faces, ignore the scenes, and.
473
00:24:34.559 --> 00:24:35.359
Or vice versa.
474
00:24:35.440 --> 00:24:38.000
So it's it's directing all of this information that I've
475
00:24:38.000 --> 00:24:41.000
been boarded with to what's what's relevant. But at the
476
00:24:41.000 --> 00:24:45.000
same time, it's also allowing us to switch if that
477
00:24:45.400 --> 00:24:48.200
we now have to go switch to another task, it says, okay,
478
00:24:48.240 --> 00:24:50.400
this is not important. Now we're going to move over
479
00:24:50.480 --> 00:24:53.359
to this this other other task. So there's many different
480
00:24:53.359 --> 00:24:55.319
components of how it can you know, how it can
481
00:24:55.400 --> 00:24:57.920
kind of control behavior, But it does all of.
482
00:24:57.880 --> 00:25:00.200
These things in this incredible way.
483
00:25:00.359 --> 00:25:03.119
We still don't completely understand, but we know that's the
484
00:25:03.160 --> 00:25:05.640
source of all of this control is coming from the
485
00:25:05.680 --> 00:25:06.680
prefrontal cortex.
486
00:25:08.160 --> 00:25:11.039
You mentioned connections between the prefrontal cortex and the body.
487
00:25:12.400 --> 00:25:15.599
That's the first I've heard of that, and I'm not
488
00:25:15.720 --> 00:25:18.640
challenging that to the contrary, I'm just intrigued by it.
489
00:25:19.240 --> 00:25:21.640
I'm aware that the hypothalamus and some of these deeper
490
00:25:21.640 --> 00:25:26.200
brain structures associated with more let's call them primitive drives,
491
00:25:26.839 --> 00:25:30.799
temperature regulation, hunger, et cetera, connect to the body. But
492
00:25:31.160 --> 00:25:33.279
what's the nature of some of the connections with the
493
00:25:33.960 --> 00:25:34.319
the body.
494
00:25:34.519 --> 00:25:36.319
Yeah, I was just sort of talking in terms of
495
00:25:36.640 --> 00:25:39.880
our knowledge of how you know, changing I wanted your
496
00:25:39.880 --> 00:25:42.640
podcasts you talked about how tms to the prefrontal cortex
497
00:25:42.680 --> 00:25:43.720
and slow heart rates.
498
00:25:43.759 --> 00:25:45.319
I meant in that and that sort of a way,
499
00:25:45.599 --> 00:25:46.680
got it? That? That that?
500
00:25:46.839 --> 00:25:51.240
Yeah, by by that, by influencing cortical function, well, obviously
501
00:25:51.279 --> 00:25:53.839
we can influence h organs like.
502
00:25:53.799 --> 00:25:57.559
The got it so through some intermediate stations. Yes, yeah,
503
00:25:57.680 --> 00:26:02.559
I mean it's you know, not too not to be hyperbolic,
504
00:26:02.599 --> 00:26:05.599
but I mean it seems like the prefrontal cortex here
505
00:26:05.599 --> 00:26:08.759
we're referring to as the frontal lobes are essentially the
506
00:26:08.799 --> 00:26:10.720
seat of what makes us human and what makes us
507
00:26:10.720 --> 00:26:13.119
functional or dysfunctional in a given context.
508
00:26:13.559 --> 00:26:14.640
Right. I mean, I.
509
00:26:14.599 --> 00:26:18.319
Recall there's a syndrome, clover Bucy syndrome, which has some
510
00:26:18.799 --> 00:26:25.000
vague similarities to how you describe frontal cortex damage. But
511
00:26:25.160 --> 00:26:30.720
there as I recall humans or animals with that syndrome
512
00:26:31.279 --> 00:26:36.400
will act in a way that's not appropriate to context
513
00:26:36.519 --> 00:26:40.119
but more inappropriate. Like they'll they'll try and eat a
514
00:26:40.119 --> 00:26:43.440
ceramic cop or draw with a piece of paper, which
515
00:26:43.519 --> 00:26:46.680
obviously won't work. It seems like with the frontal cortex,
516
00:26:47.200 --> 00:26:49.039
it knows that a pen is for writing. It just
517
00:26:49.200 --> 00:26:50.880
the person might say, yeah, I know I'm not supposed
518
00:26:50.880 --> 00:26:52.880
to write this, but I'm just gonna or write with it.
519
00:26:52.880 --> 00:26:55.000
But I'm gonna take your pen and write something inappropriate
520
00:26:55.039 --> 00:26:58.000
with it. But it's not that they people forget that
521
00:26:58.039 --> 00:27:00.839
there's that it's a pen. So it seems like it's
522
00:27:01.079 --> 00:27:05.839
drawing on so rule sets, but that something's intact.
523
00:27:06.200 --> 00:27:06.599
It's like that.
524
00:27:06.680 --> 00:27:10.960
It's not like Clover Bucy syndrome, where like animals and
525
00:27:10.960 --> 00:27:14.640
people can try and like mate with inanimate are objects,
526
00:27:15.920 --> 00:27:18.799
which is one of the more salient symptoms. I'll never
527
00:27:18.839 --> 00:27:19.559
forget that.
528
00:27:19.839 --> 00:27:21.000
Never forget that from from.
529
00:27:20.920 --> 00:27:23.200
My cognitive neuroscience courts, which you are, by the way,
530
00:27:24.079 --> 00:27:26.920
just throw that in there, so you know, so how
531
00:27:26.920 --> 00:27:28.359
should we think about this? And here I'm trying to
532
00:27:28.400 --> 00:27:30.279
get at a kind of a broader understanding of brain
533
00:27:30.319 --> 00:27:35.880
function and context specific behavior. So frontal cortex is like
534
00:27:37.160 --> 00:27:41.400
super sophisticated, but it doesn't.
535
00:27:41.119 --> 00:27:42.680
Have all the information, right.
536
00:27:42.680 --> 00:27:44.960
It seems like someone without a frontal cortex probably knows
537
00:27:45.119 --> 00:27:46.599
that you write with a pen, you don't write with
538
00:27:46.640 --> 00:27:47.359
a piece of paper.
539
00:27:48.279 --> 00:27:50.920
Yeah, I think it's you know, we think about it
540
00:27:50.960 --> 00:27:53.480
as it's you know, the frontal cortters allows us to
541
00:27:53.519 --> 00:27:56.519
take thought and move it towards action. And there's this
542
00:27:56.680 --> 00:28:01.039
disconnect between the knowledge and action and the separation of
543
00:28:01.079 --> 00:28:03.519
action from knowledge. And I guess I can reflect on
544
00:28:03.559 --> 00:28:05.720
my patients, you know, when I've seen a lot of
545
00:28:05.759 --> 00:28:09.039
patients with damage all over the brain, and all of
546
00:28:09.079 --> 00:28:13.359
the families of patients who have frontal lowe injury always
547
00:28:13.400 --> 00:28:14.279
say the same thing.
548
00:28:14.319 --> 00:28:16.400
They're just no longer that person.
549
00:28:16.559 --> 00:28:19.599
They're no longer my spouse, and no longer my best friend,
550
00:28:19.640 --> 00:28:20.559
they're no longer my father.
551
00:28:20.799 --> 00:28:21.319
Just something.
552
00:28:21.759 --> 00:28:24.559
They can't put it into words, but they're not them anymore.
553
00:28:25.039 --> 00:28:27.640
There's something has changed. Whereas if you talk to a
554
00:28:27.680 --> 00:28:30.759
patient with brocus of phasia who has this inability to speak,
555
00:28:30.759 --> 00:28:32.680
they can't get any words out. You know, this is
556
00:28:32.720 --> 00:28:38.400
a devastating problem. They're still the same person, their personality
557
00:28:38.400 --> 00:28:41.160
hasn't changed. They feel the same person. They just can't speak.
558
00:28:41.200 --> 00:28:42.880
The way they get around in the world is different.
559
00:28:43.039 --> 00:28:45.720
Or if you take a patient with pro spagnosic, which
560
00:28:45.759 --> 00:28:48.920
is this inability to recognize faces, of course the way
561
00:28:48.960 --> 00:28:52.799
they navigate around the world is difficult and it's not
562
00:28:52.880 --> 00:28:54.880
the same, but there's still the same person.
563
00:28:54.920 --> 00:28:56.119
So there's something really.
564
00:28:55.880 --> 00:28:59.559
Special about the frontal cortex that allows us to be,
565
00:29:00.160 --> 00:29:02.720
as you said, sort of who we are. And that's
566
00:29:02.720 --> 00:29:05.400
the difficult part, Like how does the frontal lobes allow
567
00:29:05.480 --> 00:29:08.799
us sort of take take who we are and translate
568
00:29:08.839 --> 00:29:12.160
that into al so we're not I guess another word
569
00:29:12.200 --> 00:29:15.480
saying of just just having knowledge is what makes us
570
00:29:15.759 --> 00:29:17.920
who we are, right, is to be able to take
571
00:29:17.960 --> 00:29:21.160
that knowledge and present it in a way that allows
572
00:29:21.240 --> 00:29:24.359
us to live life based on our intentions and our
573
00:29:24.400 --> 00:29:27.119
goals and our desires.
574
00:29:27.160 --> 00:29:31.440
So much of things like stoic philosophy and even online
575
00:29:31.680 --> 00:29:38.759
wellness culture are about having routines, you know, overcoming reflex
576
00:29:38.839 --> 00:29:43.440
by just having recipes scripts to follow each day. I
577
00:29:43.480 --> 00:29:46.759
certainly try to have my mournings be as what I
578
00:29:46.799 --> 00:29:49.599
call linear as possible, and I find it's much easier
579
00:29:49.599 --> 00:29:52.839
in the earlier part of the day to just decide
580
00:29:52.839 --> 00:29:54.400
here's what I'm gonna do right out a list, do
581
00:29:54.440 --> 00:29:56.839
things in a certain sequence. If I don't do that,
582
00:29:56.880 --> 00:29:59.759
I go nonlinear, as I refer to it, and we'll
583
00:29:59.759 --> 00:30:03.440
get distracted and things of that sort. But earlier you
584
00:30:03.480 --> 00:30:07.720
mentioned sleep deprivation can impair frontal load function. It does
585
00:30:07.759 --> 00:30:11.200
seem that as the day progresses, and certainly in the
586
00:30:11.240 --> 00:30:15.119
middle of the night, it just becomes much harder to
587
00:30:15.160 --> 00:30:19.559
control our our thinking, maybe even our behavior, but and
588
00:30:19.559 --> 00:30:23.880
certainly our emotions. Is there a frontal load regulation of
589
00:30:23.920 --> 00:30:26.160
emotional states as well? I know you have some recent
590
00:30:26.200 --> 00:30:27.440
work on this, so I love.
591
00:30:27.319 --> 00:30:27.839
To get more.
592
00:30:27.920 --> 00:30:29.640
Yeah, I mean, as I was saying earlier, the frontal
593
00:30:29.680 --> 00:30:32.640
loves is a big place, and half of it is
594
00:30:32.680 --> 00:30:35.599
involved in these high level executive functions. But the other
595
00:30:35.640 --> 00:30:38.799
half of it is is part of the limits system
596
00:30:39.240 --> 00:30:41.440
that we call it the paralymics system that's involved in
597
00:30:41.519 --> 00:30:46.119
social and emotional behavior. And so there's this intimate back
598
00:30:46.200 --> 00:30:49.039
and forth between these two areas of the cortex. If
599
00:30:49.079 --> 00:30:51.799
you have just damage to these frontal to these areas
600
00:30:51.799 --> 00:30:53.559
that are kind of in the world frontal love, you
601
00:30:53.640 --> 00:30:57.480
will have many different impairments that we would call sort
602
00:30:57.480 --> 00:31:00.720
of social or emotional appairents and they're exactly function will
603
00:31:00.759 --> 00:31:03.759
be quite normal. And then you'll have the opposite where
604
00:31:03.920 --> 00:31:06.720
patients with the lott of damage will have executive functions
605
00:31:06.720 --> 00:31:11.039
but they seem emotionally intact. But you know, in real
606
00:31:11.079 --> 00:31:13.680
life when we have both these intact, they're communicating with
607
00:31:13.759 --> 00:31:17.400
each other. So right, emotion and contacts and is going
608
00:31:17.440 --> 00:31:21.759
to influence our executive function. We make bad decisions in
609
00:31:21.799 --> 00:31:25.400
stressful situations or situations we're not comfortable with. It's it's
610
00:31:25.440 --> 00:31:27.599
where we might make a better decision if it's a
611
00:31:27.680 --> 00:31:29.039
quiet you know, kind.
612
00:31:28.839 --> 00:31:30.480
Of a quiet place.
613
00:31:32.160 --> 00:31:34.960
But it is something that we can I think you're right,
614
00:31:35.039 --> 00:31:37.720
you can. You can sort of get into a routine
615
00:31:37.799 --> 00:31:39.759
and learn how to do things, you know, if you
616
00:31:40.039 --> 00:31:42.319
have very much planned out. But what's so unique about
617
00:31:42.400 --> 00:31:44.920
us how we can be flexible and adaptable. Right when
618
00:31:45.400 --> 00:31:49.559
when something novel comes up, or there's something something unexpected
619
00:31:49.599 --> 00:31:52.519
comes up, we can adapt to it. And that's really
620
00:31:52.519 --> 00:31:55.440
what the frontal cortex is really important for, not just
621
00:31:55.480 --> 00:31:59.039
sort of making these plans routines and setting all the
622
00:31:59.119 --> 00:32:00.880
rules with being able to when things don't go.
623
00:32:00.920 --> 00:32:03.039
Right, how to write the ship right.
624
00:32:04.240 --> 00:32:09.720
I will never ask you to demonize technology. I certainly
625
00:32:09.799 --> 00:32:15.519
use a smartphone from waking till sleep, generally not in
626
00:32:15.559 --> 00:32:16.960
the middle of the night if I can avoid it,
627
00:32:17.279 --> 00:32:21.079
and I generally avoid it. But I'm trying to take
628
00:32:21.119 --> 00:32:28.000
what we've discussed this far and superimpose the notion of
629
00:32:28.039 --> 00:32:31.160
smartphones and ask what are the rules, what are the
630
00:32:31.200 --> 00:32:34.200
algorithms that we're learning when we use these devices? And
631
00:32:34.240 --> 00:32:37.680
I'm not calling them adaptive or maladaptive. They're clearly here
632
00:32:37.720 --> 00:32:39.960
to stay. They've assisted in medicine. I'm sure it makes
633
00:32:39.960 --> 00:32:43.279
it easier for doctors to communicate on the ward and
634
00:32:44.000 --> 00:32:50.519
for clinic and it so useful right, But contained in
635
00:32:50.559 --> 00:32:55.480
this small device there are things like, for instance, text messaging,
636
00:32:55.519 --> 00:32:58.359
where unlike twenty years ago, we can have four or
637
00:32:58.359 --> 00:33:02.720
five different conversations very quickly while boarding a flight. There's
638
00:33:02.759 --> 00:33:05.960
a task switching element that was just not present in
639
00:33:06.039 --> 00:33:12.759
our life prior to that. Social media, in particular, this
640
00:33:12.839 --> 00:33:15.960
notion of being able to scroll so move. If we
641
00:33:16.000 --> 00:33:21.000
really step back from this, move one's thumb and access hundreds,
642
00:33:21.000 --> 00:33:24.119
if not thousands of video content from distinct which each
643
00:33:24.160 --> 00:33:28.000
of which has a distinct context. And so I have
644
00:33:28.000 --> 00:33:32.000
to imagine that kids and adults have frontal cortices that
645
00:33:32.039 --> 00:33:37.759
are learning these rules, and the rule is move your thumbs,
646
00:33:38.480 --> 00:33:44.160
stay engaged emotions, either positive valance emotions or negative emotions.
647
00:33:44.200 --> 00:33:47.400
I mean, it's a fairly limited landscape there when you
648
00:33:47.440 --> 00:33:51.640
really think about it. But the algorithm that's learned is
649
00:33:51.880 --> 00:33:54.599
to me doesn't seem exportable. It doesn't help me prepare
650
00:33:54.640 --> 00:33:57.079
for a podcast at all. I know that for sure.
651
00:33:57.160 --> 00:33:59.559
It doesn't help me go for a run, doesn't help
652
00:33:59.559 --> 00:34:03.279
me listen in with more focused attention to a family
653
00:34:03.319 --> 00:34:07.559
member or a friend or a significant other. It may
654
00:34:07.599 --> 00:34:10.519
make me more empathic or more angry. You know, we can,
655
00:34:10.599 --> 00:34:14.519
we can speculate, but again with no with no intention
656
00:34:14.559 --> 00:34:18.440
of demonizing social media. Does it seem that that the
657
00:34:18.559 --> 00:34:22.199
algorithms that are being run in our brain? I mean,
658
00:34:22.239 --> 00:34:25.599
are they neutral? Are they positive? Are they negative? Should
659
00:34:25.639 --> 00:34:28.519
we be worried that? It doesn't seem like they translate
660
00:34:28.559 --> 00:34:30.840
to much else? They I can't see a way in
661
00:34:30.840 --> 00:34:33.719
which they help us be better people in other domains.
662
00:34:33.719 --> 00:34:36.480
Whereas reading a book line by line and then going
663
00:34:36.519 --> 00:34:38.440
back out, I didn't even remember anything from that page
664
00:34:38.440 --> 00:34:41.880
going back line by line, playing a game of squash
665
00:34:42.000 --> 00:34:44.519
or something like that. There I can see the real
666
00:34:44.599 --> 00:34:47.519
value of the rule sets that generalize.
667
00:34:48.480 --> 00:34:50.960
Yeah, I mean I can. You know, just historically, I
668
00:34:51.000 --> 00:34:53.039
grew up in a world when there was no smartphones
669
00:34:53.079 --> 00:34:55.400
as a resident, and and so one of the most
670
00:34:55.440 --> 00:34:58.000
difficult things I do in practices have to take care
671
00:34:58.000 --> 00:34:59.960
of patients in the emergency room and there's a real
672
00:35:00.079 --> 00:35:03.559
emergency someone's having un control seizures or they're having a stroke.
673
00:35:03.760 --> 00:35:06.199
And you know, doing this back in the eighties or
674
00:35:06.280 --> 00:35:08.840
nineties and early two thousands, when you went down there
675
00:35:08.880 --> 00:35:11.559
and you didn't have any smartphone, you could only rely
676
00:35:11.679 --> 00:35:14.760
on what's in your head. And I could say, now
677
00:35:14.800 --> 00:35:17.800
having the smartphone, it hasn't It doesn't help me at all.
678
00:35:17.880 --> 00:35:20.159
I never you know, it does not help me at all.
679
00:35:20.199 --> 00:35:22.199
And making the kind of decisions that I have to
680
00:35:22.199 --> 00:35:24.800
make in the emergency room, I'm trying to decide, you
681
00:35:24.840 --> 00:35:29.239
know what, what's the problem here, what's the differential diagnosis?
682
00:35:29.519 --> 00:35:31.199
How should I treat it. I'm just trying to make
683
00:35:31.519 --> 00:35:33.920
going through an algorithm, like you said, in a common
684
00:35:33.960 --> 00:35:36.159
sense way, and there's nothing on my phone that I
685
00:35:36.199 --> 00:35:38.719
can turn to to help me do that. It has
686
00:35:38.800 --> 00:35:41.679
helped with giving me knowledge, Like back in the day,
687
00:35:41.719 --> 00:35:44.039
I had to remember what the dilanthan dose was and
688
00:35:44.079 --> 00:35:45.480
have that in my head, or go look for the
689
00:35:45.480 --> 00:35:47.039
piece of paper in my pocket and so I can
690
00:35:47.119 --> 00:35:49.760
quickly pull up you know, I guess I'm a little
691
00:35:49.800 --> 00:35:52.800
bit you know, there's information that I can access that
692
00:35:52.840 --> 00:35:55.519
I don't have to worry about keeping every single dose
693
00:35:55.559 --> 00:35:57.000
in my head or keeping everything in.
694
00:35:56.920 --> 00:35:58.800
My head, just facts in my head.
695
00:35:58.880 --> 00:36:01.400
But outside of that, there's nothing I can turn to
696
00:36:01.679 --> 00:36:04.760
that it's it's making me, you know, better, making me
697
00:36:04.800 --> 00:36:07.639
make better decisions. So I don't even need my cell phone.
698
00:36:07.760 --> 00:36:09.800
I don't go searching for my cell phone. If I'm
699
00:36:09.800 --> 00:36:11.679
going to go to room, we're going to take a
700
00:36:11.840 --> 00:36:13.400
take a phone call. So I don't see how it's
701
00:36:13.679 --> 00:36:16.159
helping sort of make your frontal low It can't be
702
00:36:16.280 --> 00:36:17.079
your frontal loves.
703
00:36:17.119 --> 00:36:19.199
I mean, it's another way of saying it.
704
00:36:19.239 --> 00:36:21.280
But but on the flip side, can it help you
705
00:36:21.519 --> 00:36:23.880
optimize frontal low function technologies?
706
00:36:24.320 --> 00:36:26.559
Certainly it can. We can maybe talk about it later.
707
00:36:26.559 --> 00:36:27.760
There are there's certainly.
708
00:36:28.079 --> 00:36:31.360
That that's one way to get learned strategies is through
709
00:36:31.400 --> 00:36:35.360
a through a device that that's easily accessible and you
710
00:36:35.400 --> 00:36:36.599
know to you.
711
00:36:36.360 --> 00:36:38.719
As opposed to a book or or having a therapist
712
00:36:39.239 --> 00:36:39.840
in your house.
713
00:36:40.480 --> 00:36:43.079
Yeah, I suppose I worry that too much of my
714
00:36:43.239 --> 00:36:47.239
time and other people's time, and especially young people's time,
715
00:36:48.079 --> 00:36:54.480
is engaging in an algorithm that does not generalize for
716
00:36:54.599 --> 00:36:57.920
adaptive behavior elsewhere. And by comparison, you know, like a
717
00:36:58.599 --> 00:37:02.599
game of soccer with friends or something, it's social, social
718
00:37:02.599 --> 00:37:05.639
media is social, it's physical. Social media is not physical.
719
00:37:05.679 --> 00:37:10.320
But we'll rule that portion out. But there's a rule set,
720
00:37:10.480 --> 00:37:14.400
there's goal directed behavior. Presumably some of the things that
721
00:37:14.480 --> 00:37:17.719
happen in a game of soccer with friends translate to
722
00:37:17.840 --> 00:37:23.000
some other domain of life because it's a single context
723
00:37:23.159 --> 00:37:26.079
game of soccer, whereas with social media, I don't know
724
00:37:26.159 --> 00:37:29.679
anybody that goes and looks at one account and that's it,
725
00:37:30.079 --> 00:37:33.519
and absorbs the information, maybe comments as an interaction, and goes.
726
00:37:33.760 --> 00:37:37.559
It's hundreds of or thousands of contexts. So is there
727
00:37:37.559 --> 00:37:41.639
any risk or perhaps benefit to being able to get
728
00:37:41.679 --> 00:37:47.679
this very detailed portal into so many contexts per unit time.
729
00:37:47.880 --> 00:37:50.360
I mean, the forebrain's never had done that in the
730
00:37:50.440 --> 00:37:51.960
course of human history as far as I know.
731
00:37:53.039 --> 00:37:54.760
Yeah, I mean, I think there is a risk.
732
00:37:54.840 --> 00:37:58.159
But what pops to mind, you know, having kids, is
733
00:37:58.719 --> 00:38:03.159
watching them navigate in their cars, took places totally dependent
734
00:38:03.239 --> 00:38:05.880
on on Google Maps, and I think you're probably old
735
00:38:05.960 --> 00:38:08.360
enough to remember real maps.
736
00:38:08.079 --> 00:38:12.920
Where you love. I love maps right where you had.
737
00:38:12.800 --> 00:38:14.559
To really figure out, you know, you you had to
738
00:38:14.559 --> 00:38:16.320
go to a certain place and you had to either
739
00:38:16.360 --> 00:38:18.639
look at the map or or ask stop at a
740
00:38:18.679 --> 00:38:21.280
gas station and ask that these these these skills were
741
00:38:21.320 --> 00:38:23.599
something that you learned and you developed and it was
742
00:38:23.800 --> 00:38:26.760
problem solving and and uh, and that's all gone now,
743
00:38:26.800 --> 00:38:30.000
I mean, it's it's I wonder even if sometimes if
744
00:38:30.480 --> 00:38:33.719
if people even know the direction they're going, whether it's
745
00:38:33.760 --> 00:38:36.119
west north or what's set town they're in, because they're
746
00:38:36.159 --> 00:38:40.000
just following the directions. So I we'll see. I just
747
00:38:40.039 --> 00:38:43.679
can't imagine that that learned skill is not going to
748
00:38:43.719 --> 00:38:47.679
be detrimental to us at some point in generalizing, these
749
00:38:47.880 --> 00:38:51.119
generalize in a bad way, right as as opposed to
750
00:38:51.119 --> 00:38:55.280
a good way. So I don't Yeah, it does. It
751
00:38:55.320 --> 00:38:57.840
does definitely worry me. But like you said, there's nothing
752
00:38:57.920 --> 00:39:01.440
on the phone that helps you plan a podcast, nothing
753
00:39:01.440 --> 00:39:04.239
that helps me and they emerged room, nothing else, professor
754
00:39:04.280 --> 00:39:06.679
when he's giving a lecture. So I agree with you
755
00:39:06.760 --> 00:39:08.960
that that the sort of having your head buried in
756
00:39:09.320 --> 00:39:12.840
a cell phone. I'm not Yeah, it's I don't see
757
00:39:12.840 --> 00:39:14.519
it's being healthy for your frontal loves.
758
00:39:15.840 --> 00:39:19.639
Let's talk about working memory. Some years back but still now.
759
00:39:19.840 --> 00:39:23.599
You use working memory tasks and experiments in your laboratory.
760
00:39:23.840 --> 00:39:26.719
If you would be so kind as to explain what
761
00:39:26.760 --> 00:39:28.840
working memory is, and then I'd love to talk about
762
00:39:29.599 --> 00:39:32.000
some of the work you've done exploring the role of
763
00:39:32.039 --> 00:39:36.480
dopamine in working memory, because this is so critical to
764
00:39:36.639 --> 00:39:38.880
everyday life. And I know dopamine's a bit of a
765
00:39:38.880 --> 00:39:42.519
buzzword these days, but the listeners of this podcast anyway,
766
00:39:42.519 --> 00:39:47.000
are pretty sophisticated in terms of knowing that dopamine is
767
00:39:47.000 --> 00:39:50.639
not just about reward. It's about motivation and goal directed behavior.
768
00:39:51.039 --> 00:39:54.000
And I think dopamine intrigues for a good reason that
769
00:39:54.119 --> 00:39:57.960
it does govern a lot of our quality of life.
770
00:39:58.320 --> 00:40:00.840
So what's working memory?
771
00:40:01.880 --> 00:40:04.320
Yeah, I mean working memory. It's interesting. I started studying
772
00:40:04.320 --> 00:40:05.440
it about thirty years.
773
00:40:05.280 --> 00:40:07.599
Ago, and I don't think I realized how important it
774
00:40:07.760 --> 00:40:08.639
was when I started.
775
00:40:08.679 --> 00:40:10.239
But what we mean by working memory is this.
776
00:40:10.239 --> 00:40:13.480
Ability to hold information in mind when it's no longer
777
00:40:13.480 --> 00:40:16.159
accessible to us. So if you tell me your telephone
778
00:40:16.199 --> 00:40:18.920
number and I have to put it into my phone.
779
00:40:19.079 --> 00:40:21.000
You know, it's no longer there you just told me.
780
00:40:21.400 --> 00:40:23.719
But I'll hold it in my working memory until I
781
00:40:23.719 --> 00:40:26.800
can punch it into my phone. It doesn't have to
782
00:40:26.800 --> 00:40:28.719
be something that comes from the outside world. I could
783
00:40:28.800 --> 00:40:31.639
hold up you know, I can pull up my own
784
00:40:31.920 --> 00:40:33.559
If I'm filling out a form and I want to
785
00:40:33.559 --> 00:40:35.559
pull up my SOL security number, I can hold that
786
00:40:35.639 --> 00:40:36.840
in mind too until I.
787
00:40:36.800 --> 00:40:37.440
Put it down.
788
00:40:37.559 --> 00:40:41.119
So when you think about it, it's a very important,
789
00:40:42.039 --> 00:40:45.760
you know, ability that we have that we do very flawlessly.
790
00:40:45.960 --> 00:40:49.000
And what I've learned more about working memory is the
791
00:40:49.000 --> 00:40:51.960
working part of it. It's not just this passive holding
792
00:40:51.960 --> 00:40:55.239
information of mind, but it's being able to do things
793
00:40:55.239 --> 00:40:58.280
with the information. It's being able to you know, when
794
00:40:58.320 --> 00:41:01.119
we do a bath problem, which we don't do that
795
00:41:01.199 --> 00:41:02.840
much now that we have calculators, but if you do
796
00:41:02.880 --> 00:41:05.079
that in your head, you're able to sort of manipulate
797
00:41:05.119 --> 00:41:08.159
the information and do the different parts of the problem.
798
00:41:08.239 --> 00:41:10.960
Or even if you're you know, you're trying to find
799
00:41:11.000 --> 00:41:13.559
someone in a crowd and you're holding onto some face,
800
00:41:13.599 --> 00:41:14.719
You're able to hold.
801
00:41:14.480 --> 00:41:16.800
That face in mind and cross check it.
802
00:41:16.800 --> 00:41:20.320
And search and and so there's there's operations to working memory.
803
00:41:20.360 --> 00:41:24.000
It's not just you know, it's not just this passive maintenance.
804
00:41:24.000 --> 00:41:26.239
So when we start to think about working memory in
805
00:41:26.280 --> 00:41:28.559
that way, we started to realize how important it is
806
00:41:28.599 --> 00:41:30.000
for it's you know, I think of it as the
807
00:41:30.000 --> 00:41:34.840
foundation for cognition. Just think about reading comprehension. You can't
808
00:41:34.960 --> 00:41:37.599
understand this conversation if you can't hold in mind what's
809
00:41:37.639 --> 00:41:39.800
going on, you know, earlier in the in the conversation,
810
00:41:39.920 --> 00:41:41.920
or when you're reading a book, you know, remembering the
811
00:41:41.960 --> 00:41:46.920
sentence before it. So it just predicts all these abilities
812
00:41:47.000 --> 00:41:51.840
that allows us to read, to a plan, to organize,
813
00:41:51.880 --> 00:41:54.599
and all the sort of executive functions that we're doing. Right,
814
00:41:54.599 --> 00:41:56.280
we have to hold in mind rules, we have to
815
00:41:56.320 --> 00:41:58.280
hold in mind goals, we have to hold in mind
816
00:41:59.199 --> 00:42:03.320
all of these things, or just carry out behavior, you know.
817
00:42:03.360 --> 00:42:06.280
So it's really come a long way in terms of
818
00:42:06.320 --> 00:42:07.400
how people are thinking about it.
819
00:42:07.880 --> 00:42:10.760
I know that Matt Walker said that, like.
820
00:42:10.920 --> 00:42:13.000
You know, sleep is our superpower, but I guess one
821
00:42:13.000 --> 00:42:15.360
way to sort of use his term. While we're awake,
822
00:42:15.519 --> 00:42:18.920
working memory is really our superpower because it allows us
823
00:42:18.960 --> 00:42:21.960
to translate, as we said, sort of our knowledge into
824
00:42:21.960 --> 00:42:25.960
action by holding this information in mind as we're thinking
825
00:42:26.000 --> 00:42:26.920
about what we want to do.
826
00:42:27.599 --> 00:42:30.000
If we're going to think about dopamine in the context
827
00:42:30.000 --> 00:42:34.559
of working memory, is dopamine an accelerator on working memory?
828
00:42:34.719 --> 00:42:37.719
Is it a facilitator? I mean, what is dopamine doing
829
00:42:37.760 --> 00:42:39.480
for working memory? And maybe we could talk a little
830
00:42:39.519 --> 00:42:42.920
bit about the circuitry. I've talked about dopamine before on
831
00:42:42.960 --> 00:42:45.280
this podcast, but there's a good chance that some of
832
00:42:45.280 --> 00:42:47.480
the people listening to this haven't heard those episodes. So
833
00:42:47.800 --> 00:42:50.840
maybe we could just quickly review the three major circuits
834
00:42:50.840 --> 00:42:53.079
for dopamine and the one that's relevant for working memory.
835
00:42:53.320 --> 00:42:55.639
Yeah, let me start with the working memory, the circuitry
836
00:42:55.679 --> 00:42:58.840
for working memory, because one of the important things about
837
00:42:58.840 --> 00:43:02.360
working memory is the other type of memory is long
838
00:43:02.440 --> 00:43:05.719
term memory. It is you can Working memory is short lived.
839
00:43:05.719 --> 00:43:07.840
It's only as long as you're able to rehearse it
840
00:43:07.920 --> 00:43:09.079
and then it disappears.
841
00:43:09.119 --> 00:43:10.960
Whereas what we call long term memory.
842
00:43:10.960 --> 00:43:14.760
If I remembering what you had for breakfast or your vacation,
843
00:43:14.920 --> 00:43:18.400
this is information that gets consolidated and gets put into
844
00:43:19.079 --> 00:43:21.480
a more durable form that we call long term memory.
845
00:43:21.480 --> 00:43:23.960
And the interesting thing about memory is that these are
846
00:43:24.039 --> 00:43:28.039
separate systems. Everything from working memory just doesn't pass into.
847
00:43:27.880 --> 00:43:28.679
Long term memory.
848
00:43:28.599 --> 00:43:32.400
There there are two completely different systems and two completely
849
00:43:32.440 --> 00:43:34.639
different parts of the brain that seem to control it.
850
00:43:35.400 --> 00:43:39.440
So working memory, the frontal cortex seems to be very
851
00:43:39.440 --> 00:43:43.639
important for working memory. When we are holding information in line,
852
00:43:43.920 --> 00:43:47.039
the neurons, the brain cells in the frontal lobes are
853
00:43:47.119 --> 00:43:50.079
active and they stay kind of active as long as
854
00:43:50.079 --> 00:43:53.920
we're holding on that information, and they're more active when
855
00:43:53.920 --> 00:43:59.519
the information is relevant, and if we get distracted, they'll
856
00:43:59.519 --> 00:44:01.920
get less active. So kind of the frontal lobes kind
857
00:44:01.920 --> 00:44:06.039
of track your you know, track the memory that you're
858
00:44:06.119 --> 00:44:09.679
holding in mind. Another important thing about the circuitry is
859
00:44:09.719 --> 00:44:12.440
that if we're holding in mind, say digits, you know
860
00:44:12.440 --> 00:44:15.199
it's the phone number, Well, that information is in your
861
00:44:15.199 --> 00:44:18.039
back of the brain, and so the frontal lobes is
862
00:44:18.079 --> 00:44:20.679
sort of keeping information in the back of the brain
863
00:44:20.719 --> 00:44:24.079
active because it's connected to the visual areas, it's it's
864
00:44:24.119 --> 00:44:26.960
able to sort of keep that information active. And so
865
00:44:27.559 --> 00:44:30.000
what we've learned is that there's not these buffers in
866
00:44:30.039 --> 00:44:33.280
the brain where you know, if you're holding verbal information,
867
00:44:33.320 --> 00:44:35.920
it's in this little buffer, and if you're holding visual information,
868
00:44:35.960 --> 00:44:39.079
it's in another buffer. The whole brain acts as a buffer,
869
00:44:39.119 --> 00:44:41.599
and the frontal lobe can call up any part of
870
00:44:41.639 --> 00:44:44.039
the brain and keep that part of the brain active
871
00:44:44.079 --> 00:44:46.719
as it's as it's you know, as it's trying to
872
00:44:46.719 --> 00:44:49.960
hold this information in line. So the mechanism for working
873
00:44:49.960 --> 00:44:54.320
memory is just this persistent neural activity within the frontal lobes.
874
00:44:54.679 --> 00:44:56.480
And so then the question is what does dope mean
875
00:44:57.079 --> 00:44:58.119
do well?
876
00:44:58.119 --> 00:44:58.639
Don't mean?
877
00:44:58.760 --> 00:45:01.039
Is one of the neuromodu layers that are made in
878
00:45:01.039 --> 00:45:03.679
the brain stem and it projects up to different parts
879
00:45:03.719 --> 00:45:06.199
of the brain. There's a system that goes up into
880
00:45:06.360 --> 00:45:08.320
what we call the basil gangula, which is important for
881
00:45:08.400 --> 00:45:11.199
motor function, and there's another doperritic system that goes up
882
00:45:11.239 --> 00:45:14.880
to the frontal lobes. And what was discovered was that
883
00:45:14.960 --> 00:45:20.039
if you deplete dope mean working memory drops you get
884
00:45:20.039 --> 00:45:23.119
a significant impairment working memory. If you deplete dope mean,
885
00:45:23.199 --> 00:45:26.159
and if you replace it, then.
886
00:45:26.000 --> 00:45:27.599
Your working memory will be improved.
887
00:45:27.760 --> 00:45:31.000
And so dope means seems to be a modulator to
888
00:45:31.119 --> 00:45:37.039
help this persistent activity stay persistent, you know, during the
889
00:45:37.079 --> 00:45:40.119
time that you need to keep this information in mind.
890
00:45:40.599 --> 00:45:46.360
Am I reaching too far to drawn analogy between dopamine's
891
00:45:46.400 --> 00:45:50.400
role and working memory, that is to keep information online,
892
00:45:50.920 --> 00:45:55.039
and the other established role of dopamine, which is for movement,
893
00:45:55.280 --> 00:45:59.039
for the generation of smooth movement, as evidenced by conditions
894
00:45:59.079 --> 00:46:02.840
like Parkinson's where people lack dopaminergic neurons or have damage
895
00:46:02.840 --> 00:46:05.559
to dope ergic neurons and have you know, challenges in
896
00:46:05.639 --> 00:46:10.239
generating smooth movement. What I'm essentially asking is can we
897
00:46:10.280 --> 00:46:16.159
think of dopamine as facilitating physical movement through one circuit
898
00:46:16.440 --> 00:46:21.840
but also kind of mental movement thought movement. I'm thinking
899
00:46:22.239 --> 00:46:24.840
for those just listening and not watching, I'm kind of
900
00:46:24.880 --> 00:46:28.039
rubbing my index and middle finger against my thumb, is
901
00:46:28.360 --> 00:46:31.280
just keeping something online. It's sort of a movement of
902
00:46:31.320 --> 00:46:34.440
thought or information and then you kind of chuck it
903
00:46:34.480 --> 00:46:36.320
away and bring about the next information.
904
00:46:36.480 --> 00:46:37.000
Is that is that?
905
00:46:37.239 --> 00:46:37.400
Yeah?
906
00:46:37.440 --> 00:46:38.840
I think that's a good way of thinking about it.
907
00:46:38.880 --> 00:46:40.599
And one might wonder at well, how can don't mean
908
00:46:40.719 --> 00:46:43.960
be important for memory but also be important for movement?
909
00:46:44.039 --> 00:46:46.440
And it's really simple. It's just that it's acting on
910
00:46:46.519 --> 00:46:50.440
different circuits. The neurons that go to the motor areas
911
00:46:50.480 --> 00:46:53.639
that carry don't mean will will when dope mean is expressed,
912
00:46:53.639 --> 00:46:56.599
there then and boosted there, then it will be involved
913
00:46:56.599 --> 00:46:59.039
in movement and lack of don't mean in the basil
914
00:46:59.039 --> 00:47:00.800
gag it will lead to neural lot of those disorders
915
00:47:00.920 --> 00:47:05.320
like Parkins's disease that has severe movement difficulty. But when
916
00:47:05.320 --> 00:47:09.440
it's acting in the frontal cortex and expressing the frontal cortex,
917
00:47:09.519 --> 00:47:11.480
then it's going to improve working memory. So it's just
918
00:47:11.800 --> 00:47:15.199
it's just the nature of where the circuits are, where
919
00:47:15.239 --> 00:47:18.000
the dope meine is, that's that's allowing it to have
920
00:47:18.039 --> 00:47:20.920
different kinds of actions, and that's for all transmitters. The
921
00:47:20.960 --> 00:47:24.239
reason why astyll coline seems to be more important for
922
00:47:24.559 --> 00:47:28.679
long term memories because it's projecting to the hippocampus, which
923
00:47:28.760 --> 00:47:31.199
was we know is another area that's important for memory,
924
00:47:31.199 --> 00:47:35.039
and that's why asctyl colin doesn't boost your working memory,
925
00:47:35.079 --> 00:47:37.039
but dopemine does and vice versa.
926
00:47:37.800 --> 00:47:40.519
So drilling a little bit more deeply into the role
927
00:47:40.559 --> 00:47:43.599
of dopamine and working memory, you did some really lovely
928
00:47:43.679 --> 00:47:48.400
experiments showing that if people who have low levels of
929
00:47:48.480 --> 00:47:53.519
dopamine increase their dopamine pharmacologically. I think the drug that
930
00:47:53.599 --> 00:47:58.480
was used was bromacryptine. That working memory improves. Conversely, if
931
00:47:58.599 --> 00:48:05.880
one depletes dopamine pharmacologically, working memory gets worse. But as
932
00:48:05.920 --> 00:48:11.880
I recall, there was an important baseline that is important
933
00:48:11.880 --> 00:48:13.800
because it really mattered in terms of the ALCO meaning
934
00:48:13.840 --> 00:48:16.960
if somebody already had relatively high levels of dopamine in
935
00:48:17.000 --> 00:48:23.199
this circuit, increasing dopamine further with bromacryptine didn't impart a benefit.
936
00:48:23.280 --> 00:48:26.039
It might have even made their working memory worse. So
937
00:48:26.079 --> 00:48:28.440
there's a kind of inverted U shape function to this.
938
00:48:30.519 --> 00:48:34.079
How does one know whether or not their baseline dopamine
939
00:48:34.199 --> 00:48:39.280
is low, medium, or high? Ergo, how do they know
940
00:48:39.320 --> 00:48:42.039
whether or not that they would want to explore going
941
00:48:42.039 --> 00:48:44.679
about increasing dopamine through any number of different approaches.
942
00:48:45.119 --> 00:48:50.000
Right, Well, most people probably have optimal dopamine, but there's
943
00:48:50.039 --> 00:48:53.679
a significant percentage that probably have too little or maybe
944
00:48:53.719 --> 00:48:57.559
too much. And it's unfortunately we can't measure it in
945
00:48:57.840 --> 00:48:59.840
the blood. There isn't a blood test that I'm a
946
00:48:59.840 --> 00:49:03.840
way that can measure. Don't mean because it's stuck in
947
00:49:04.000 --> 00:49:04.599
it suck in the.
948
00:49:04.599 --> 00:49:07.920
Brain, prifteral dopamine in the blood doesn't is not a
949
00:49:07.920 --> 00:49:08.559
good readout.
950
00:49:08.760 --> 00:49:09.760
Is not a good readout.
951
00:49:09.880 --> 00:49:12.920
Yeah, and especially when you're talking about dop't mean in
952
00:49:13.280 --> 00:49:16.280
areas like prefrontal cortex, and so we don't have a
953
00:49:16.280 --> 00:49:20.079
good read out there. There's there's invasive procedures like positron
954
00:49:20.119 --> 00:49:24.559
emission tomography where we can inject a radio isotope that
955
00:49:24.719 --> 00:49:27.000
tags don't mean, and then we can measure how much
956
00:49:27.079 --> 00:49:29.280
we can do a scan that actually shows us how
957
00:49:29.320 --> 00:49:30.079
much dope mean.
958
00:49:30.519 --> 00:49:31.119
This scan was.
959
00:49:31.119 --> 00:49:35.360
Originally developed to show Parkins's disease, that you can diagnose
960
00:49:35.400 --> 00:49:38.280
Parkins disease by showing that there's there's less dope mean
961
00:49:38.519 --> 00:49:42.719
in patients that Parking is by looking at this scan. Obviously,
962
00:49:42.719 --> 00:49:46.239
it's invasive, you're injecting a real isotope, it's expensive, and
963
00:49:46.280 --> 00:49:48.840
it's not something we could all do, but we had
964
00:49:48.920 --> 00:49:51.519
used it to show that it correlates very strongly with
965
00:49:51.599 --> 00:49:54.679
your working memory capacity. So how much information you can
966
00:49:54.719 --> 00:49:56.960
hold online, if you can hold four or five or
967
00:49:57.000 --> 00:50:01.199
six letters when I do a span task correlated with
968
00:50:01.239 --> 00:50:03.079
how much dope mean we can see in the pet skin,
969
00:50:03.199 --> 00:50:05.719
So that that would be a way that we could
970
00:50:05.760 --> 00:50:06.079
do it.
971
00:50:06.800 --> 00:50:08.639
So if you were to read out a string of
972
00:50:08.920 --> 00:50:12.320
a few numbers or letters, and I can remember all
973
00:50:12.360 --> 00:50:18.559
of those a few moments later, perhaps perhaps my baseline
974
00:50:18.599 --> 00:50:23.360
dopamine levels are moderate in the in the normal range,
975
00:50:23.440 --> 00:50:26.559
whereas if I couldn't keep that online, that might be
976
00:50:26.920 --> 00:50:30.079
might be reflective of lower baseline dopamine levels.
977
00:50:30.159 --> 00:50:32.159
Is that right, Yeah, it's a it's a very strong
978
00:50:32.239 --> 00:50:34.599
proxy for dope means. So if your your working americ
979
00:50:34.679 --> 00:50:39.960
capacity is seven letters or numbers when I say four, three, seven, one, five,
980
00:50:40.119 --> 00:50:43.039
zero six, if you get those three seven types them
981
00:50:43.079 --> 00:50:46.159
all right very quickly, you probably have more dope baseline
982
00:50:46.199 --> 00:50:47.800
dope mean than than someone.
983
00:50:47.519 --> 00:50:51.239
Who has five. There, So it's a proxy.
984
00:50:50.880 --> 00:50:53.079
For measuring one's something, so that that's one way of
985
00:50:53.119 --> 00:50:55.079
doing it, and that's actually how we did it in
986
00:50:55.119 --> 00:51:00.800
our original studies. We we actually group into visuals based
987
00:51:00.800 --> 00:51:04.360
on whether their capacity, based on this behavioral measure, was
988
00:51:04.440 --> 00:51:07.079
high or low. And like you said, those who work
989
00:51:07.440 --> 00:51:10.679
that can only hold five or six letters, we gave
990
00:51:10.679 --> 00:51:14.000
them bromo cryptine, which was the dope nerves gagonist. We
991
00:51:14.039 --> 00:51:17.280
improved their working memory, We got them into sort of
992
00:51:17.320 --> 00:51:20.719
an optal level. But those who were already high, we
993
00:51:20.800 --> 00:51:23.360
actually made them, we work got them worse.
994
00:51:23.559 --> 00:51:25.679
And the moral of that story was that more is
995
00:51:25.760 --> 00:51:26.519
just not better.
996
00:51:26.960 --> 00:51:30.280
We're trying to get people optimal. And so the real
997
00:51:30.360 --> 00:51:32.159
question is is you know, if we want to get
998
00:51:32.159 --> 00:51:35.440
people optimal, Like you were inferring, you have to know.
999
00:51:35.480 --> 00:51:37.920
What there don't mean is where are you on this
1000
00:51:38.079 --> 00:51:39.880
inverted you curve.
1001
00:51:40.039 --> 00:51:41.400
Another way of doing.
1002
00:51:41.159 --> 00:51:45.800
It is through a through genetics studies, So we had
1003
00:51:46.400 --> 00:51:50.079
don't mean all nerve transmitters have to be broken down
1004
00:51:50.119 --> 00:51:52.480
and re uptaked into the into the.
1005
00:51:52.400 --> 00:51:54.159
Brain cell in order to be used again.
1006
00:51:54.559 --> 00:51:57.079
And there's different ways of doing it, and some cells
1007
00:51:57.840 --> 00:52:01.519
it gets transported back into the brain cell and other
1008
00:52:01.599 --> 00:52:04.639
places there's an enzyme that breaks it down. Well, there's
1009
00:52:04.639 --> 00:52:08.800
an enzyme called COMPT that breaks down dope being in
1010
00:52:08.840 --> 00:52:13.760
the prefrontal cortex specifically, in a large percent of individuals,
1011
00:52:13.840 --> 00:52:18.480
that enzyme is either overactive or underactive. Probably about twenty
1012
00:52:18.519 --> 00:52:22.599
five percent of individuals it's overactive and another twenty five
1013
00:52:22.639 --> 00:52:25.760
percent it's underactive. So probably half the population.
1014
00:52:25.840 --> 00:52:28.239
Now this is going to vary depend on.
1015
00:52:30.000 --> 00:52:31.800
Where you live and where you come from and things,
1016
00:52:31.840 --> 00:52:36.000
but maybe half the population either has an underactive enzyme
1017
00:52:36.159 --> 00:52:39.719
or overactive enzyme. If you have an underactive enzyme, then
1018
00:52:39.760 --> 00:52:42.559
actually more dope means sits around and you actually have
1019
00:52:42.639 --> 00:52:44.559
more dope meane than others, and if you have an
1020
00:52:44.599 --> 00:52:47.880
overactive enzyme, it's the opposite. So we've actually shown that
1021
00:52:47.920 --> 00:52:51.480
if you now go in genotype people with a simple
1022
00:52:51.519 --> 00:52:55.360
saliva test and figure out do they have this genetic
1023
00:52:55.400 --> 00:52:58.360
what we call polymorphism, where just one amino acid gets
1024
00:52:58.480 --> 00:53:03.440
changed in the enzyme becomes either active or underactive, we
1025
00:53:04.079 --> 00:53:08.079
can do the same thing as grouping them by their capacity.
1026
00:53:08.199 --> 00:53:11.119
Those that have the low dope mean we will make
1027
00:53:11.159 --> 00:53:14.039
them better, and those who have sort of baseline high
1028
00:53:14.039 --> 00:53:16.199
dope meine will make them worse.
1029
00:53:18.119 --> 00:53:22.360
Super interesting. Maybe we could talk about bromacryptine a little bit,
1030
00:53:22.519 --> 00:53:28.400
and I'm not encouraging people to run out and take bromacryptine. Bromocryptine,
1031
00:53:28.559 --> 00:53:33.400
as you mentioned, is a dopamine agonist, relatively short acting.
1032
00:53:33.639 --> 00:53:35.840
Yeah, four or five hours, six hours.
1033
00:53:35.639 --> 00:53:38.239
So kicks in about it ninety minutes after as I
1034
00:53:38.280 --> 00:53:39.719
recall you saying I've never taken it.
1035
00:53:41.039 --> 00:53:43.039
How do people feel when they're on broma cryptine?
1036
00:53:43.079 --> 00:53:45.559
I mean when I hear dopamine agonists, I mean there
1037
00:53:45.559 --> 00:53:48.840
are a lot of illicit drugs like cocaine, methamphetamine that
1038
00:53:48.840 --> 00:53:52.960
are increased dopamine. But then again, chocolate, sex and food
1039
00:53:53.039 --> 00:53:56.159
increase dopamine, but the kinetics, the time course, and the
1040
00:53:56.239 --> 00:53:59.679
levels are different for each of those things. Dopamine, of course,
1041
00:53:59.719 --> 00:54:04.760
being a currency of motivation and reward, not directly related
1042
00:54:04.760 --> 00:54:05.719
to anyone compound.
1043
00:54:05.719 --> 00:54:09.360
But I would think that.
1044
00:54:09.360 --> 00:54:13.639
Based on the data you just described that, and given
1045
00:54:13.639 --> 00:54:14.960
the fact that there are a number of people out
1046
00:54:14.960 --> 00:54:18.320
there with challenges and working memory, attention, task switching, etc.
1047
00:54:18.639 --> 00:54:21.679
That there would be a strong interest on the part
1048
00:54:21.719 --> 00:54:24.800
of the pharmaceutical companies at least and certainly the general
1049
00:54:24.840 --> 00:54:29.920
public in things like from a cryptine to increase dopamine
1050
00:54:29.960 --> 00:54:32.639
to increase working memory, given it as our superpower.
1051
00:54:33.559 --> 00:54:35.639
Yeah, I mean, one of the most disappointing things to
1052
00:54:35.719 --> 00:54:38.840
me in my career has been that pharmaceutic companies have
1053
00:54:38.920 --> 00:54:41.960
not picked up on this idea that we could improve
1054
00:54:42.079 --> 00:54:45.159
cognition and very specifically improved kind of process with very
1055
00:54:45.159 --> 00:54:49.480
specific neuromodulators. The discovery that depletion of dope meane and
1056
00:54:49.519 --> 00:54:52.440
not other transmitters impairs working memory was made in nineteen
1057
00:54:52.480 --> 00:54:53.239
seventy nine.
1058
00:54:54.360 --> 00:54:57.719
When I heard Pat Gonorkey's talk about.
1059
00:54:57.480 --> 00:54:59.719
This as a resident, I was just amazed that there
1060
00:54:59.760 --> 00:55:04.039
could be a single transmitter can change a single behavior.
1061
00:55:04.079 --> 00:55:07.480
I was seeing very complicated behavioral deficits, and it just
1062
00:55:07.480 --> 00:55:09.880
seemed impossible to me that there could be such a
1063
00:55:09.880 --> 00:55:13.400
tight link between a single you know, a single neuromodulator
1064
00:55:13.440 --> 00:55:15.480
or a single cognit of process and just open the
1065
00:55:15.519 --> 00:55:18.320
door for me that this really could be an incredibly
1066
00:55:18.719 --> 00:55:23.840
beneficial therapy for anyone with executive function or frontal low function. So,
1067
00:55:24.480 --> 00:55:27.880
but unfortunately, there's never been a pharmacial company that's tried
1068
00:55:27.920 --> 00:55:32.920
to develop a drug for improving cognition to this day, and.
1069
00:55:32.880 --> 00:55:35.280
They I mean, it's crazy for several reasons. One is
1070
00:55:35.280 --> 00:55:38.039
that the data are clearly there too. These drugs are
1071
00:55:38.039 --> 00:55:40.320
already established. It's not like they have to go through
1072
00:55:40.320 --> 00:55:44.559
safety trials again, that's already done. But mostly because regardless
1073
00:55:44.559 --> 00:55:47.559
of whether one is a fan of the pharmaceutical industry
1074
00:55:47.639 --> 00:55:50.480
or hates it, the pharmaceutical industry and principle can make
1075
00:55:50.480 --> 00:55:51.960
a ton of money doing this, so I would think
1076
00:55:52.000 --> 00:55:54.400
that they'd be heavily incentivized to do it. So why
1077
00:55:54.400 --> 00:55:56.719
have they turned a blind eye on this?
1078
00:55:56.920 --> 00:55:57.440
I'm not sure.
1079
00:55:57.480 --> 00:56:01.440
I mean, when I realized that I could test these
1080
00:56:01.920 --> 00:56:06.000
drugs in healthy individuals, that they were if I gave
1081
00:56:06.039 --> 00:56:08.719
them in low enough doses. They were safe, and I
1082
00:56:08.760 --> 00:56:10.920
had so much experience of them in patience that I
1083
00:56:10.920 --> 00:56:16.400
felt comfortable doing it. Then I started asking pharma fool companies,
1084
00:56:16.440 --> 00:56:17.760
you know, do you want to get involved here?
1085
00:56:17.960 --> 00:56:20.360
Can we can? This should be done. I can't do
1086
00:56:20.480 --> 00:56:21.360
this by myself.
1087
00:56:21.400 --> 00:56:24.079
We need to have real trials and real studies of
1088
00:56:24.119 --> 00:56:27.119
how this will help. You know, and just was you know,
1089
00:56:27.280 --> 00:56:29.920
their eyes would always cross and never never got any
1090
00:56:30.199 --> 00:56:31.039
any sort of traction.
1091
00:56:31.119 --> 00:56:33.239
It always went back to sort of disease.
1092
00:56:33.360 --> 00:56:36.480
You know what, what disease are you curing?
1093
00:56:36.559 --> 00:56:38.480
You know what? What's the market for it? Is it
1094
00:56:38.559 --> 00:56:39.559
a parking disease? Thing?
1095
00:56:39.599 --> 00:56:41.960
Is an Alzheimer's disease thing? And this has been a
1096
00:56:42.000 --> 00:56:45.599
general problem with neurology. It's very disease centric. It's always
1097
00:56:45.599 --> 00:56:47.920
sort of and it's always focused on, you know, how
1098
00:56:47.960 --> 00:56:50.599
can we develop a treatment for Alzheimer's or traumatic branjury
1099
00:56:50.679 --> 00:56:52.440
or stroke, as opposed to how can we develop a
1100
00:56:52.480 --> 00:56:58.239
treatment for working memory dysfunction, which is a problem across diseases.
1101
00:56:58.360 --> 00:57:01.000
So the answer to your earlier says, these drugs are
1102
00:57:01.159 --> 00:57:03.920
very safe. They we give them in such low doses
1103
00:57:03.960 --> 00:57:04.760
to healthy individuals.
1104
00:57:04.800 --> 00:57:05.599
They don't even know.
1105
00:57:06.199 --> 00:57:09.599
They can't even tell the difference between the placebo and
1106
00:57:09.639 --> 00:57:12.119
the drug. Really, they don't even know which one they're on.
1107
00:57:12.320 --> 00:57:15.000
So they're not buzzing thinking like, oh this feels good. No,
1108
00:57:15.280 --> 00:57:16.360
my working memory is better.
1109
00:57:16.400 --> 00:57:18.000
They have no idea. They don't even know their working
1110
00:57:18.079 --> 00:57:20.280
memories better. It's all we show them that their working
1111
00:57:20.320 --> 00:57:21.159
memory is better.
1112
00:57:21.239 --> 00:57:24.039
So yeah, so they're truly blind to what's going on.
1113
00:57:25.119 --> 00:57:28.639
Broma kryptine is but one of the dopamine agonists. I
1114
00:57:28.679 --> 00:57:32.639
can think of a few other cabergoline like other things
1115
00:57:32.679 --> 00:57:37.639
like that. Do any of these dopamine agonists exert this
1116
00:57:38.480 --> 00:57:41.719
impact on working memory or is it? Does it vary
1117
00:57:41.719 --> 00:57:45.599
by drug because different dopamine agonists sort of hit different
1118
00:57:45.639 --> 00:57:47.400
receptor pathways and things like that.
1119
00:57:47.679 --> 00:57:49.360
Yeah, no, it's not specifically the drug.
1120
00:57:49.480 --> 00:57:51.960
I mean, the reason for bromo kryptine is that it's
1121
00:57:52.000 --> 00:57:54.320
the oldest and it's the one I was most comfortable with.
1122
00:57:54.360 --> 00:57:55.599
I had to be comfortable with it.
1123
00:57:55.519 --> 00:57:59.239
Clinically before I to give it to undergraduates at Pander Berkeley.
1124
00:57:59.320 --> 00:58:03.400
So there's nothing special, but other agonists works. Similarly, there's
1125
00:58:03.440 --> 00:58:05.960
a there's a drug that's developer partents, which is a
1126
00:58:06.000 --> 00:58:09.360
compt inhibitor which actually inhibits this this enzyme that we're
1127
00:58:09.400 --> 00:58:13.119
talking about, and that that also will improve will have
1128
00:58:13.199 --> 00:58:17.679
the same function. There's been some future work that NORP
1129
00:58:17.719 --> 00:58:21.679
and neephrine also seems to be helpful with working memory. Uh,
1130
00:58:22.079 --> 00:58:26.079
it's not as maybe not as potent as as the
1131
00:58:26.119 --> 00:58:28.840
dope nergic. And that's the point I want to make
1132
00:58:28.880 --> 00:58:31.559
another another disappointing thing about this whole field at the
1133
00:58:31.559 --> 00:58:35.840
pharmacology of cognition. You know, I wrote a paper as
1134
00:58:35.880 --> 00:58:37.840
a residence. You know, sometimes you're tending to say, hey,
1135
00:58:37.880 --> 00:58:39.599
can you write this review paper for us?
1136
00:58:39.599 --> 00:58:41.559
And I wrote one as a resident.
1137
00:58:41.360 --> 00:58:43.639
Called the Pharmacology Cognition where I looked at all the
1138
00:58:43.639 --> 00:58:49.480
animal literature on you know, uh, giving neuromodulators as solcholine,
1139
00:58:49.559 --> 00:58:53.360
won't dope mean or whatever, and and there was a
1140
00:58:53.360 --> 00:58:55.639
lot of there was a lot of animal literature sort
1141
00:58:55.639 --> 00:58:58.159
of supporting that this would work in humans. But was
1142
00:58:58.960 --> 00:59:02.159
more striking to me was that it wasn't always just
1143
00:59:02.239 --> 00:59:04.400
a single neuro transmitter.
1144
00:59:04.920 --> 00:59:06.239
There were studies where you'd.
1145
00:59:06.079 --> 00:59:08.559
Give don't mean and it wouldn't do anything, and give
1146
00:59:08.599 --> 00:59:10.760
actyal colon it wouldn't do anything. But if you gave
1147
00:59:10.800 --> 00:59:13.760
a low dose of both, it would it would be
1148
00:59:13.800 --> 00:59:17.440
really effective. So these you know, these church systems don't
1149
00:59:17.440 --> 00:59:20.440
act in isolation, so we need to also study sort
1150
00:59:20.440 --> 00:59:23.039
of how the combinations work. And that's where another you know,
1151
00:59:23.079 --> 00:59:26.360
where the pharmas wool companys have the infrastructure to do
1152
00:59:26.400 --> 00:59:27.159
these kind of things.
1153
00:59:27.199 --> 00:59:29.039
It's very hard to do in a single lad.
1154
00:59:28.840 --> 00:59:32.719
To to do multiple drugs at one time, you know,
1155
00:59:32.760 --> 00:59:34.920
and then try and look at trying to determine all
1156
00:59:34.920 --> 00:59:36.159
the different interactions.
1157
00:59:36.440 --> 00:59:39.960
Maybe we could talk about a couple of other drugs
1158
00:59:39.960 --> 00:59:43.920
that are legal or have and have FDA approval or
1159
00:59:44.039 --> 00:59:48.119
known to be safe in the right context that it
1160
00:59:48.159 --> 00:59:51.800
seems would fit the bill here. For improving working memory,
1161
00:59:51.840 --> 00:59:57.079
one is well beutrinne grow prior.
1162
00:59:57.639 --> 00:59:59.760
I can never pronounce that as far as I know.
1163
00:59:59.800 --> 01:00:00.079
It's a.
1164
01:00:01.880 --> 01:00:05.840
Epinephrin or nor epenefrin agonist. You just mentioned that increasing
1165
01:00:05.840 --> 01:00:08.760
epinephrin may have a positive impact in working memory and
1166
01:00:08.800 --> 01:00:11.519
to some extent a dopamine agonist. Is there any evidence
1167
01:00:11.559 --> 01:00:14.800
that well beautrin can improve working memory?
1168
01:00:15.119 --> 01:00:18.039
Yeah, and anything that boosts norap and nephrin can do it.
1169
01:00:18.039 --> 01:00:21.280
The one that we've used that's most used is guandphysine
1170
01:00:21.360 --> 01:00:23.960
which is actually a blood pressure medication. So that's starting
1171
01:00:24.000 --> 01:00:26.119
to gain some traction. In fact, I think there was
1172
01:00:26.159 --> 01:00:29.199
a study with COVID with brain fog for COVID showing
1173
01:00:29.199 --> 01:00:33.440
that improved symptoms with it. So there's actually some trials
1174
01:00:33.480 --> 01:00:36.280
now that are looking at guanphysine. And so I would
1175
01:00:36.320 --> 01:00:40.679
say anything that boosts norapenephrine would be would be helpful.
1176
01:00:41.000 --> 01:00:42.599
But then again I don't I don't want to leave
1177
01:00:42.599 --> 01:00:47.719
out the other transmitters serotonin, you know, increasing serotonin, increasing
1178
01:00:47.719 --> 01:00:51.280
acid coling, boosts other cognitive processes, and then you know
1179
01:00:51.360 --> 01:00:53.760
in a way they can help working memory. We talked
1180
01:00:53.760 --> 01:00:56.440
about working memory being being this foundation. Well, if if
1181
01:00:56.480 --> 01:00:59.679
you give vascylcholine and it kind of boosts memory, well
1182
01:00:59.719 --> 01:01:01.480
that indirectly.
1183
01:01:00.920 --> 01:01:02.000
Help your executive function.
1184
01:01:02.119 --> 01:01:05.360
Or if you give a drug that improves your focus,
1185
01:01:05.480 --> 01:01:08.480
then that can indirectly help you know, working memory. So
1186
01:01:08.880 --> 01:01:10.880
what I'm really pushing for is is not just a
1187
01:01:11.000 --> 01:01:12.760
single you know, it's going to be one drug. You know,
1188
01:01:12.800 --> 01:01:15.440
one drug, it's going to be a cocktail, and we
1189
01:01:15.559 --> 01:01:18.440
have to not only figure out what the cocktail is,
1190
01:01:18.480 --> 01:01:20.679
but also figure out who we're giving it to, what's
1191
01:01:22.039 --> 01:01:24.239
you know, link it to the person's own makeup of
1192
01:01:24.280 --> 01:01:25.679
their own neurochemistry.
1193
01:01:25.800 --> 01:01:27.000
When we get to a point where.
1194
01:01:26.840 --> 01:01:30.039
We'll know we can map outs or everyone's don't mean
1195
01:01:30.079 --> 01:01:33.480
europe inefferent serotonin levels, so then we'll make real progress
1196
01:01:33.920 --> 01:01:35.960
in helping them, because right now I sort of say
1197
01:01:36.519 --> 01:01:38.880
with my students, what we're doing is just it's just
1198
01:01:38.920 --> 01:01:41.079
like cutting open the skull and just sort of pouring
1199
01:01:41.119 --> 01:01:44.639
it onto the brain. It's not actually but actually doing it.
1200
01:01:44.679 --> 01:01:47.400
But it seems that way we're not. The precision is
1201
01:01:47.440 --> 01:01:48.320
not there yet.
1202
01:01:49.239 --> 01:01:53.880
Well, it's great that you developed this cognitive task that
1203
01:01:53.960 --> 01:01:56.800
can be a proxy for dopamine levels. The cognitive task
1204
01:01:56.840 --> 01:02:01.400
again being how many number letters ring somebody can remember,
1205
01:02:02.280 --> 01:02:06.519
basically working memory performance. There are a lot of tests
1206
01:02:06.559 --> 01:02:10.880
out there that claim they can assess dopamine and serotonin
1207
01:02:10.920 --> 01:02:13.679
acuit of coling levels from a blood draw. I've heard
1208
01:02:13.719 --> 01:02:16.840
of the Dutch test. I've never taken it, But a
1209
01:02:16.880 --> 01:02:21.000
few minutes ago you said that really one needs to
1210
01:02:21.039 --> 01:02:24.599
do positrono mission tomography imaging, which is fairly labor intensive.
1211
01:02:24.639 --> 01:02:27.559
Most people don't have access to one of those. It's
1212
01:02:27.559 --> 01:02:32.639
a clinical tool. So there are behavioral proxies. There's neuroimaging,
1213
01:02:33.119 --> 01:02:35.800
but also to my knowledge, I don't know that there's
1214
01:02:35.840 --> 01:02:38.360
any blood draw that will say, hey, your serotonin levels
1215
01:02:38.400 --> 01:02:43.119
are lower, your dopamine levels are moderate, your et cetera.
1216
01:02:43.199 --> 01:02:44.840
There are a lot of companies that market these, But
1217
01:02:44.960 --> 01:02:47.920
are you aware of any clinical or other tools for
1218
01:02:48.039 --> 01:02:51.719
getting an accurate read of neurotransmitter levels in a person's
1219
01:02:51.719 --> 01:02:53.400
brain aside from neuroimaging.
1220
01:02:54.119 --> 01:02:54.360
No.
1221
01:02:54.440 --> 01:02:57.840
And it's even more complicated than it seems because the
1222
01:02:57.880 --> 01:03:01.000
doperenor system is complicated because it's not only just the
1223
01:03:01.039 --> 01:03:04.320
preformal cortex as we talked about, it's also the basal ganglia.
1224
01:03:04.599 --> 01:03:08.119
And so not only do we have to measure dope
1225
01:03:08.119 --> 01:03:11.159
mean just generally levels, we have to measure the balance
1226
01:03:11.199 --> 01:03:14.039
of the dope mean in the striatum and the and
1227
01:03:14.079 --> 01:03:16.760
the preformal cortex. There's there's a model of don't mean
1228
01:03:17.800 --> 01:03:21.480
function and its relation executive function that has to do
1229
01:03:21.559 --> 01:03:24.000
with sort of the balance between these two systems. That
1230
01:03:24.119 --> 01:03:28.719
don't mean in the prefrontal cortex is promoting sort of stability.
1231
01:03:28.760 --> 01:03:33.159
It's it's keeping information in mind, keeping these representations stable,
1232
01:03:33.800 --> 01:03:36.320
whereas the don't mean in the basil ganglia, what it's
1233
01:03:36.400 --> 01:03:40.480
doing is allowing you to update and refresh, you know,
1234
01:03:40.599 --> 01:03:43.679
the information that that you're holding in mind. This sort
1235
01:03:43.679 --> 01:03:46.599
of stability versus flexibility. So if you have too much
1236
01:03:46.599 --> 01:03:48.400
DoPT mean informal cortex, it could lead to a very
1237
01:03:48.480 --> 01:03:50.320
rigid state where you don't.
1238
01:03:50.159 --> 01:03:50.880
Let anything in.
1239
01:03:50.960 --> 01:03:53.519
And if you have too much don't mean the stratum
1240
01:03:53.519 --> 01:03:55.039
and then you get too flexible, then you can get
1241
01:03:55.119 --> 01:03:58.480
very distractable. So there's this sort of balance of dope means.
1242
01:03:58.480 --> 01:04:00.480
So it's not just how much don't mean you have
1243
01:04:00.599 --> 01:04:03.199
in your brain, it's it's how much what's the balance
1244
01:04:03.239 --> 01:04:04.840
of that don't mean. So I don't see a blood
1245
01:04:04.840 --> 01:04:08.280
tests ever giving us that information, but I do see
1246
01:04:08.280 --> 01:04:12.320
there being a brain test that that can that can
1247
01:04:12.320 --> 01:04:15.079
give us this kind of information of the two, or
1248
01:04:15.079 --> 01:04:17.760
at least a proxy for it. So what I was
1249
01:04:17.800 --> 01:04:20.480
thinking about when you were talking about asking this question.
1250
01:04:20.599 --> 01:04:23.880
You know, for example, if you measure pupillary pupil dilation,
1251
01:04:24.039 --> 01:04:27.880
that's a pretty good proxy for for the neurogenetic system.
1252
01:04:28.199 --> 01:04:30.880
Right, So at a given people will wonder what how
1253
01:04:30.880 --> 01:04:33.920
to do it. We're not gonna go into too much
1254
01:04:33.960 --> 01:04:36.519
detail here, but at a given brightness in the room,
1255
01:04:36.599 --> 01:04:39.639
what we call luminance, the pupil tends to be smaller
1256
01:04:39.639 --> 01:04:42.599
when it's bright and larger when it's you're in a
1257
01:04:42.639 --> 01:04:47.039
dim room, that's sort of obvious. But at a given luminance,
1258
01:04:47.360 --> 01:04:52.559
the more alert aroused somebody is arousal as a general
1259
01:04:52.639 --> 01:04:56.719
term here, not not talking about a particular kind of arousal,
1260
01:04:57.360 --> 01:04:59.960
then the pupil tends to be more dilated, it gets big,
1261
01:05:00.199 --> 01:05:04.920
or the more neuropineffron is in the system. So if
1262
01:05:04.920 --> 01:05:09.840
somebody's pupils are really big in bright light, that person's
1263
01:05:09.880 --> 01:05:13.519
got a lot of a epinephrin adrenaline in their system.
1264
01:05:13.920 --> 01:05:16.000
Do you use this clinically like when someone comes into the.
1265
01:05:16.079 --> 01:05:18.320
Those big old pupils pupil and.
1266
01:05:18.280 --> 01:05:20.079
You're like, Okay, they're probably on a stimulant.
1267
01:05:20.320 --> 01:05:20.519
Yeah.
1268
01:05:20.519 --> 01:05:22.719
I mean a lot of what neurology does is try
1269
01:05:22.760 --> 01:05:25.360
to look for these windows into the brain, and so
1270
01:05:25.440 --> 01:05:27.199
I think there are a number of windows into the
1271
01:05:27.239 --> 01:05:29.280
brain that we're going to be able to develop that
1272
01:05:29.360 --> 01:05:32.119
can reflect these neural monetory systems. So that's why I've
1273
01:05:32.119 --> 01:05:35.639
been so interested in developing biomarkers, because really what a
1274
01:05:35.719 --> 01:05:39.960
neural biomarker is is trying to develop something you can
1275
01:05:40.000 --> 01:05:43.400
measure easily and simply and cheaply with you know, what
1276
01:05:43.679 --> 01:05:46.800
gives you information about how the brain is working. And
1277
01:05:46.800 --> 01:05:48.719
so that's a you know, that's a neurop and efferent
1278
01:05:48.719 --> 01:05:52.920
biomarker working marry capacities that don't mean biomarker. And we're
1279
01:05:52.920 --> 01:05:55.960
getting better at that, but again we're not putting enough
1280
01:05:56.039 --> 01:05:59.159
emphasis on it in my opinion, to really sort of help,
1281
01:05:59.599 --> 01:06:01.239
you know, improve brain health.
1282
01:06:01.679 --> 01:06:03.920
Have you ever tried broumacryptine.
1283
01:06:04.280 --> 01:06:05.480
Very early on?
1284
01:06:05.639 --> 01:06:08.280
But it's such a low do you know at the
1285
01:06:08.320 --> 01:06:11.039
dose that my subjects were getting, But like I said,
1286
01:06:11.039 --> 01:06:13.599
it doesn't it's so low you don't feel anything. And
1287
01:06:13.599 --> 01:06:17.320
I should say with even with patients that take it,
1288
01:06:17.400 --> 01:06:21.400
they rarely get any side effects sometimes with these drugs
1289
01:06:21.400 --> 01:06:24.880
because there's perferle don't mean they can get nausea, vong
1290
01:06:25.039 --> 01:06:29.679
but it's extremely well tolerated. You don't get any anything
1291
01:06:29.880 --> 01:06:30.719
feeling from it.
1292
01:06:30.760 --> 01:06:32.159
Does it change reaction time?
1293
01:06:32.519 --> 01:06:33.199
It does?
1294
01:06:33.280 --> 01:06:35.760
And that's always the question of how much of this
1295
01:06:35.840 --> 01:06:38.000
is that we're just sort of speeding up, We're just
1296
01:06:38.000 --> 01:06:40.360
sort of making them faster. But for all the work
1297
01:06:40.400 --> 01:06:43.000
we've done, it's pretty convincing that it's it's not just
1298
01:06:43.239 --> 01:06:45.079
how fast you're doing it, you're doing it better.
1299
01:06:46.320 --> 01:06:51.599
You might find this entertaining. Some years ago, I learned
1300
01:06:52.199 --> 01:06:58.880
that athletes were taking broumacryptine pre Olympics and in the Olympics.
1301
01:06:58.920 --> 01:07:02.519
I think it's a banned substance now. And the athletes
1302
01:07:02.559 --> 01:07:04.119
that were taking it. Don't ask me how I know this,
1303
01:07:04.360 --> 01:07:06.920
but I could tell you offline and I'm not one
1304
01:07:06.960 --> 01:07:09.440
of these athletes, nor was I supplying the broma cryptine.
1305
01:07:09.840 --> 01:07:12.880
We're using it because they were sprinters, and it turns
1306
01:07:12.920 --> 01:07:14.960
out that a lot of the sprint races are one
1307
01:07:15.639 --> 01:07:18.360
by being first out the blocks. There are other factors
1308
01:07:18.400 --> 01:07:21.239
as well, but that reaction time, you know, hundreds of milliseconds,
1309
01:07:21.320 --> 01:07:27.440
or the difference between podium and no podium, and bromocryptine
1310
01:07:27.480 --> 01:07:29.800
was one of the drugs used. It was not on
1311
01:07:29.840 --> 01:07:32.760
the band substance list. Just a reminder that every Olympics
1312
01:07:32.760 --> 01:07:34.599
you see there are lots of things being used that
1313
01:07:34.639 --> 01:07:36.440
are not on the band substance list. And I'm not
1314
01:07:36.440 --> 01:07:38.119
trying to be disparaging. I think there's just a lot
1315
01:07:38.119 --> 01:07:42.280
of interest in augmenting neuromodulation for nervous system function. Bromocryptine
1316
01:07:42.320 --> 01:07:43.960
was top of the list at that time. I think
1317
01:07:43.960 --> 01:07:47.280
it's on the band list now. There's a lot of
1318
01:07:48.519 --> 01:07:51.880
use of pharmacology now on college campuses and in high
1319
01:07:51.880 --> 01:07:54.559
school and even in elementary schools, and sometimes by parents
1320
01:07:54.599 --> 01:07:57.239
for their kids to try and improve cognitive function, most
1321
01:07:57.239 --> 01:08:00.800
typically the use of adderall vivants, riddle in and other
1322
01:08:00.840 --> 01:08:03.840
stimulants which are neuadridenergic dopaminergic agonists.
1323
01:08:04.840 --> 01:08:05.480
Okay, so.
1324
01:08:07.840 --> 01:08:12.079
With the disclaimer, caveat whatever you want to call it, that,
1325
01:08:12.239 --> 01:08:14.880
you know, those decisions should always be made with a
1326
01:08:14.920 --> 01:08:22.560
trained psychiatrist monitoring things. What are your thoughts about pharmacology
1327
01:08:22.640 --> 01:08:26.359
for enhancing cognitive function? Given that the landscape of society
1328
01:08:26.439 --> 01:08:30.920
is challenging and people want to perform well, they need
1329
01:08:30.960 --> 01:08:34.239
to be able to focus. We've got smartphones distracting us
1330
01:08:34.239 --> 01:08:38.600
and to some extent, you know, one could say, oh, well,
1331
01:08:38.600 --> 01:08:41.199
it's cheating to use pharmacology, but a cup of coffee
1332
01:08:41.600 --> 01:08:46.279
is a bit of a neuroadrenergic agonist and certainly can
1333
01:08:46.279 --> 01:08:48.039
improve my focus, as long as I don't drink too
1334
01:08:48.079 --> 01:08:48.479
much of it.
1335
01:08:49.720 --> 01:08:50.479
Yeah, what are your thoughts?
1336
01:08:50.880 --> 01:08:50.960
Just?
1337
01:08:51.319 --> 01:08:52.960
Yeah, I think it, you know, it kind of gets
1338
01:08:53.000 --> 01:08:56.600
back to what we talked about there being an optimal
1339
01:08:57.119 --> 01:09:00.479
you know, optimal level of dopamin in your brain. I
1340
01:09:00.560 --> 01:09:03.199
think if you think about it as just more and
1341
01:09:03.239 --> 01:09:05.760
more and more is better, and that more is better,
1342
01:09:05.920 --> 01:09:09.039
then there's really no and there's really no how do
1343
01:09:09.079 --> 01:09:10.479
you know how much you should be taking?
1344
01:09:10.520 --> 01:09:12.399
This certain was run in the eighties.
1345
01:09:12.439 --> 01:09:16.439
It's called the cocaine culture of Wall Street in the eighties.
1346
01:09:16.439 --> 01:09:18.439
That was their movies about it. And it doesn't lead
1347
01:09:18.479 --> 01:09:19.760
to good places.
1348
01:09:19.399 --> 01:09:23.359
Right right, So so I'm all for optimizing function. Uh,
1349
01:09:23.720 --> 01:09:25.680
I want to optimize brain health. And if you have
1350
01:09:25.760 --> 01:09:28.800
an underactive you know, enzyme that's not that that makes
1351
01:09:28.800 --> 01:09:31.359
you don't mean levels, then I'm all for trying to
1352
01:09:31.399 --> 01:09:35.119
optimize that along with everything else we need to optimize
1353
01:09:35.119 --> 01:09:35.520
in the brain.
1354
01:09:35.600 --> 01:09:39.359
So if we could figure out who who is sort.
1355
01:09:39.159 --> 01:09:41.800
Of on the lower end and boost them up, I'm
1356
01:09:41.840 --> 01:09:43.600
all for that. The problem is we don't know if
1357
01:09:43.640 --> 01:09:46.119
they're on the high end, and some of these athletes
1358
01:09:46.159 --> 01:09:49.399
were actually making themselves worse. We know for sure, I mean,
1359
01:09:49.520 --> 01:09:53.359
these are healthy ten and Berkeley undergraduates, that we made
1360
01:09:53.359 --> 01:09:56.560
them worse on working memory tests, you know, increasing by
1361
01:09:56.560 --> 01:10:00.840
increasing their dopemain just a little amount, just tip them over,
1362
01:10:00.960 --> 01:10:02.279
just a little little amount.
1363
01:10:02.439 --> 01:10:04.720
And uh and so we you.
1364
01:10:04.680 --> 01:10:08.000
Know, without the knowing, then it just it seems like
1365
01:10:08.079 --> 01:10:10.560
it's not well informed you're going to be taking it.
1366
01:10:10.640 --> 01:10:12.840
The other thing is, if we're going to do this,
1367
01:10:12.880 --> 01:10:14.920
we should do it right. I think drugs like Adderall
1368
01:10:14.960 --> 01:10:18.319
and riddl and you know, they were developed because they
1369
01:10:18.359 --> 01:10:21.800
helped patients, but they weren't nationally developed with knowing how
1370
01:10:21.840 --> 01:10:22.920
exactly they worked.
1371
01:10:23.000 --> 01:10:25.880
I mean that's how the foreign s soole company worked too.
1372
01:10:26.039 --> 01:10:28.199
Yeah, I mean, it just it works, so let's do it. And
1373
01:10:28.239 --> 01:10:31.000
I'm all for that as a physician. But if I
1374
01:10:31.039 --> 01:10:34.079
had my choice, uh, you know, drugs that boost up
1375
01:10:34.159 --> 01:10:36.760
multiples all the catechola means the ones that boost up
1376
01:10:36.800 --> 01:10:39.520
dope mean, epineffrin and normal and effort, and I would
1377
01:10:39.560 --> 01:10:43.359
steer away from those because you have no control over
1378
01:10:43.479 --> 01:10:46.159
how you're moduling the system. Again, I was sort of
1379
01:10:46.199 --> 01:10:48.920
talking about a cocktail. It it may be a little
1380
01:10:48.920 --> 01:10:51.159
bit of dope mean and a little more normal and effort,
1381
01:10:51.279 --> 01:10:53.119
But if you give to take something like riddle and anteroal,
1382
01:10:53.119 --> 01:10:55.520
you just get the same amount. So it's kind of
1383
01:10:55.720 --> 01:10:58.439
if I was to start to sort of experiment. Then
1384
01:10:58.439 --> 01:11:00.840
I except you, I wouldn't use add all a riddle
1385
01:11:00.880 --> 01:11:02.720
and as the as the drug that I think would
1386
01:11:02.720 --> 01:11:05.000
help well, even though they're clinically serve you. So I
1387
01:11:05.079 --> 01:11:08.000
use things like prom kryptine and quanfacine where they can
1388
01:11:08.039 --> 01:11:11.119
modulate a very specific drug. And then and then yeah,
1389
01:11:11.199 --> 01:11:14.359
then the goal is to optimize, and that's what we're
1390
01:11:14.359 --> 01:11:18.399
trying to do with cognitive therapy, therapy and everything's sleeping
1391
01:11:18.479 --> 01:11:21.880
better and better, nutritional. All of these are aiming to optimize,
1392
01:11:21.920 --> 01:11:27.600
not you know, reach some super human potential.
1393
01:11:27.600 --> 01:11:31.279
Right, just bring out the best in people's abilities. Right,
1394
01:11:31.479 --> 01:11:34.520
And I'm I'm so glad you mentioned sleep. I would say,
1395
01:11:34.520 --> 01:11:37.439
you know, sleep is the the bedrock. It's the foundation
1396
01:11:37.479 --> 01:11:40.079
of mental health, physical health, and performance. I mean, without that,
1397
01:11:40.880 --> 01:11:43.760
pharmacology might bridge you for an afternoon, but you're going
1398
01:11:43.840 --> 01:11:48.319
to pay the piper somehow. Our friend and colleague Matt
1399
01:11:48.319 --> 01:11:51.560
Walker obviously has been beating that drum for a while.
1400
01:11:53.119 --> 01:11:55.920
What about drugs like modaphanil, which are thought to be
1401
01:11:56.199 --> 01:12:02.039
true cognitive enhancers as opposed to drugs that just kind
1402
01:12:02.079 --> 01:12:06.159
of are designed to ramp up levels of alertness, as
1403
01:12:06.359 --> 01:12:07.680
many of the drugs we're discussing do.
1404
01:12:08.119 --> 01:12:08.960
Yeah, it's hard to know.
1405
01:12:09.079 --> 01:12:13.439
I mean, I think certain drugs just improve general abilities,
1406
01:12:13.520 --> 01:12:16.520
either they speed how fast you can process it or
1407
01:12:16.520 --> 01:12:19.800
how efficient you can process or narrow the focus of
1408
01:12:19.840 --> 01:12:23.600
your tension, and that just helps all abilities. So it's
1409
01:12:23.640 --> 01:12:25.600
hard to say. I think just this has to be
1410
01:12:25.640 --> 01:12:29.760
more work on really understanding what specifically you know, these
1411
01:12:29.840 --> 01:12:30.439
drugs are doing.
1412
01:12:30.479 --> 01:12:33.119
That's why grow encrypting the The dopernerg story.
1413
01:12:32.920 --> 01:12:36.439
Has been so interesting because it's a very specific effect
1414
01:12:36.520 --> 01:12:38.840
with a very specific mechanism. I like to see that
1415
01:12:39.119 --> 01:12:41.720
be done with with other neuromodulators.
1416
01:12:42.279 --> 01:12:44.239
Maybe we could talk a bit about some of the
1417
01:12:44.279 --> 01:12:48.560
disease conditions that you treat and the role of working
1418
01:12:48.600 --> 01:12:53.039
memory and dopamine in those conditions, as well as other
1419
01:12:53.279 --> 01:12:56.479
transmitter systems. You know, one subject that we haven't talked
1420
01:12:56.479 --> 01:13:01.439
about on this podcast previously but is of tremendous interest
1421
01:13:01.479 --> 01:13:06.199
to people is traumatic brain injury or concussion, even mild concussion.
1422
01:13:06.880 --> 01:13:10.359
And before we're recording the day, we were talking about football.
1423
01:13:10.920 --> 01:13:13.880
But I just want to remind people that football is
1424
01:13:14.079 --> 01:13:18.319
just one instance of an opportunity to get a concussion
1425
01:13:18.399 --> 01:13:21.199
or traumatic brain injury. Most traumatic brain injury. Concussion is
1426
01:13:21.239 --> 01:13:23.560
not due to football. It just gets a lot of
1427
01:13:23.560 --> 01:13:29.359
the attention. But you've got bicycle accidents, car accidents, playground accidents.
1428
01:13:30.720 --> 01:13:34.359
Maybe you could list off a few more, but how
1429
01:13:34.359 --> 01:13:37.920
common is TBI and concussion, and maybe you could just
1430
01:13:38.600 --> 01:13:41.079
perhaps list out some of the other situations where you
1431
01:13:41.119 --> 01:13:43.319
see a lot of this that it's a bit more
1432
01:13:43.359 --> 01:13:45.960
cryptic that people wouldn't necessarily think that sport or that
1433
01:13:46.399 --> 01:13:48.520
population gets TBI, but they do.
1434
01:13:49.119 --> 01:13:53.520
Yeah, I think concussion is much more prevalent than we realize,
1435
01:13:53.600 --> 01:13:56.399
and the numbers have gone up and up, not because
1436
01:13:56.680 --> 01:14:00.840
it's becoming more commoncious it's becoming more recognized, and I think,
1437
01:14:01.159 --> 01:14:04.159
you know, we underestimated and trivialized.
1438
01:14:03.640 --> 01:14:04.920
Sort of what a concussion is.
1439
01:14:05.000 --> 01:14:08.079
You know, is that it's just a you know, something
1440
01:14:08.119 --> 01:14:11.239
that is you know, just you're going to recover from it.
1441
01:14:11.319 --> 01:14:14.239
I mean, still the old school thinking by a lot
1442
01:14:14.279 --> 01:14:17.640
of neurologists is that everyone gets better within a couple
1443
01:14:17.720 --> 01:14:19.960
of months, you know, just just wait it out and
1444
01:14:20.000 --> 01:14:24.159
you'll get better. That's just the normal time course of concussion.
1445
01:14:24.199 --> 01:14:26.680
But as we've studied it more, we realize that there's
1446
01:14:26.720 --> 01:14:29.960
actually quite a large percentage of people who year out
1447
01:14:30.000 --> 01:14:33.560
there's still suffering problems. They still feel like they're not
1448
01:14:33.760 --> 01:14:36.960
mentally clear, and they still are sensitive to light, and
1449
01:14:37.000 --> 01:14:40.479
they still feel a little dizzy, and just the symptoms,
1450
01:14:40.479 --> 01:14:43.560
you know, the host of symptoms that just one year
1451
01:14:43.640 --> 01:14:46.920
later after a concussion where they didn't even lose consciousness,
1452
01:14:46.960 --> 01:14:49.680
you know, that's something that they may not have even
1453
01:14:49.760 --> 01:14:54.319
talked to their doctor about is is lingering. And so
1454
01:14:54.359 --> 01:14:57.560
it's a real this we call this persistent post concussion syndrome.
1455
01:14:57.560 --> 01:15:00.000
And that's the most worrisome to me because it is
1456
01:15:00.000 --> 01:15:03.479
it's true that most concussions will recover. Luckily, the brain
1457
01:15:03.600 --> 01:15:07.439
is incredibly resilient, incredibly plastic, and it will heal itself.
1458
01:15:08.199 --> 01:15:10.920
But there are a lot of patients where it just persists,
1459
01:15:10.960 --> 01:15:13.439
and those are the most worsome to me because we
1460
01:15:13.560 --> 01:15:16.760
don't have very good interventions to try and help that,
1461
01:15:16.840 --> 01:15:19.880
and I don't think we take these patients very seriously
1462
01:15:19.960 --> 01:15:23.520
when they're complaining of something that seems very vague and
1463
01:15:23.560 --> 01:15:26.239
not very specific to most doctors.
1464
01:15:26.880 --> 01:15:30.079
What do you tell a patient who comes in and
1465
01:15:30.319 --> 01:15:34.880
has clearly had a concussion, mild or severe concussion. You
1466
01:15:34.920 --> 01:15:37.680
have maybe car accident, maybe a sports injury, maybe they
1467
01:15:37.680 --> 01:15:40.479
were knocked out cold, maybe not, but they're having some headaches,
1468
01:15:40.479 --> 01:15:45.279
some photophobia, sensitivity light, just feeling not right. I've had
1469
01:15:45.800 --> 01:15:49.600
a couple of these, unfortunately, and you just feel off,
1470
01:15:49.960 --> 01:15:54.279
you don't feel quite right, and some of that MANIFESTSOS
1471
01:15:54.319 --> 01:15:57.159
focus issues. This was some years ago. I like to
1472
01:15:57.159 --> 01:15:59.399
think I'm through it. I've had scans and I'm good,
1473
01:16:00.239 --> 01:16:05.119
Thank goodness. But what do you tell them besides don't
1474
01:16:05.159 --> 01:16:05.880
get another one?
1475
01:16:06.760 --> 01:16:07.039
Yeah?
1476
01:16:07.039 --> 01:16:10.399
Well, first of all, I explain what a concussion is.
1477
01:16:10.560 --> 01:16:13.159
What I found in neurology. A lot of what patients
1478
01:16:13.159 --> 01:16:14.960
want to know is just they just want to understand
1479
01:16:14.960 --> 01:16:18.359
their problem, not walking in expecting a cure. It just
1480
01:16:18.359 --> 01:16:21.319
just like understanding what it is. Having someone understand what
1481
01:16:21.720 --> 01:16:26.119
happened to them is very helpful and comforting. So what
1482
01:16:26.119 --> 01:16:28.960
we mean by concussion, and we in the clinical world
1483
01:16:28.960 --> 01:16:31.399
we use mile traumatic brain ury kind of synon honestly
1484
01:16:31.520 --> 01:16:35.399
with concussions.
1485
01:16:33.840 --> 01:16:37.359
It basically is a tearing of axons. It's the brain.
1486
01:16:37.479 --> 01:16:40.720
The brain cells have these long fibers that communicate with
1487
01:16:40.760 --> 01:16:43.439
each other and they're called axons, and when the brain
1488
01:16:43.520 --> 01:16:47.159
violently moves forward and backwards, if you're in a car,
1489
01:16:47.199 --> 01:16:49.560
accident and you have your seatbelt on and you suddenly hit,
1490
01:16:49.680 --> 01:16:52.720
you go from fifty to zero, your head violently goes
1491
01:16:52.760 --> 01:16:56.199
forward and violently goes backwards, and that angular force actually
1492
01:16:56.279 --> 01:17:00.520
tears and stretches axons in the brain. So if you've
1493
01:17:00.520 --> 01:17:03.720
had a concussion, you have torn some axons. I mean,
1494
01:17:03.800 --> 01:17:06.680
luckily we have billions of them, and so if you
1495
01:17:06.800 --> 01:17:10.439
tear a couple of thousand, you will will recover. But
1496
01:17:10.560 --> 01:17:14.000
you have torn axons. It's a real neurologic, it's a
1497
01:17:14.039 --> 01:17:18.680
real brain injury. Even if if even if you haven't
1498
01:17:18.760 --> 01:17:21.640
lost consciousness and you've only had symptoms for a couple
1499
01:17:21.680 --> 01:17:25.039
of days, but there and there's a correlation. The longer
1500
01:17:25.079 --> 01:17:28.439
you've lost consciousness and the longer symptoms last, the more
1501
01:17:28.479 --> 01:17:31.840
axons you've you've torn. This kind of a direct relationship
1502
01:17:31.880 --> 01:17:36.039
between the two. So the so the mechanism is these
1503
01:17:36.119 --> 01:17:39.079
torn accents. So now nursoes don't communicate with each other,
1504
01:17:39.319 --> 01:17:42.039
and you know that the brain, different brain reangers are
1505
01:17:42.039 --> 01:17:45.439
not communicating with each other. So and it turns out
1506
01:17:45.439 --> 01:17:47.920
the most common place for axons to tears in the
1507
01:17:48.000 --> 01:17:50.720
in the frontal lobes. And so now we talked about
1508
01:17:50.760 --> 01:17:53.039
all these things that the front lobes do to orchestrate
1509
01:17:53.079 --> 01:17:55.399
the rest of the brain. While it doesn't, it has
1510
01:17:55.479 --> 01:17:58.520
some injured pathways, and that's why a lot of the
1511
01:17:58.600 --> 01:18:01.640
symptoms that patient have are these kind of.
1512
01:18:01.600 --> 01:18:03.560
Mild executive symptoms.
1513
01:18:03.640 --> 01:18:07.000
This mental fogness that they're describing is this ability, just
1514
01:18:07.079 --> 01:18:10.600
this non ability to to get things get things done.
1515
01:18:10.720 --> 01:18:13.640
They don't lose knowledge of who they don't forget their
1516
01:18:13.720 --> 01:18:16.079
name or you know, forget where they live, or lose
1517
01:18:16.119 --> 01:18:18.119
memories from the past or anything like that, but they
1518
01:18:18.239 --> 01:18:21.079
just they don't officially get things done as well as
1519
01:18:21.119 --> 01:18:22.800
they used to. It only takes a little bit of
1520
01:18:22.800 --> 01:18:25.479
a drop, right You. People think you have to have
1521
01:18:25.520 --> 01:18:29.279
a big drop and performance to have a real life impact.
1522
01:18:29.319 --> 01:18:31.520
Just a one percent drop and you're you're having a
1523
01:18:31.600 --> 01:18:35.520
hard time doing your podcast or teaching a lecture or
1524
01:18:35.520 --> 01:18:36.319
whatever you might do.
1525
01:18:37.239 --> 01:18:43.840
A one percent drop sounds like a frighteningly small change
1526
01:18:44.600 --> 01:18:49.680
required to negatively impact life. So how about a poor
1527
01:18:49.760 --> 01:18:52.199
night's sleep. I mean, what kind of drop in prefrontal
1528
01:18:52.239 --> 01:18:55.479
cortical function are we looking at from a Let's say
1529
01:18:55.520 --> 01:18:58.439
I normally get seven or eight hours or six to
1530
01:18:58.479 --> 01:19:01.439
eight hours, and I suddenly only get three or four.
1531
01:19:01.560 --> 01:19:03.560
Are we talking a significant detriment?
1532
01:19:04.079 --> 01:19:07.239
I do think so, I do think that, yeah, that
1533
01:19:07.239 --> 01:19:11.119
that that it is significant. That's a poor night's sleep.
1534
01:19:11.199 --> 01:19:13.319
And and we all know, we all notice that. I mean,
1535
01:19:13.359 --> 01:19:16.920
it's very it's very obvious. I mean, and you and
1536
01:19:17.119 --> 01:19:19.640
and you know, it's hard to sort of quantify. I'm
1537
01:19:19.680 --> 01:19:22.239
a baseball fan, so I can quantify it, like if
1538
01:19:22.279 --> 01:19:24.720
you think about it in a picture and how fast
1539
01:19:24.760 --> 01:19:28.960
they throw, you know, a small drop for them, someone
1540
01:19:28.960 --> 01:19:30.920
who's throwing one hundred miles an hour. Just a small
1541
01:19:31.000 --> 01:19:35.279
drop turns them, you know, from really elite to someone mediocre.
1542
01:19:35.359 --> 01:19:37.760
Maybe it's more of a ten percent drop, but it's
1543
01:19:37.760 --> 01:19:41.000
still relatively small drop can have a huge impact. I
1544
01:19:41.000 --> 01:19:43.520
think people think that just because you're a little bit off,
1545
01:19:43.640 --> 01:19:45.479
that's not going to that's not a big deal. You
1546
01:19:45.640 --> 01:19:47.560
kind of you kind of work through it. And that's
1547
01:19:47.600 --> 01:19:50.880
what most doctors say. You just just just plow through it.
1548
01:19:51.000 --> 01:19:52.520
Just just work your way through it. You're going to
1549
01:19:52.560 --> 01:19:56.520
get better. And as opposed to saying, yeah, you really
1550
01:19:56.560 --> 01:20:00.439
had a brain injury, this is what happened. We need
1551
01:20:00.479 --> 01:20:03.680
to rehabilitate you, just like we would do if you
1552
01:20:03.720 --> 01:20:07.159
tore your anti crucial ligament. I don't know why tearing
1553
01:20:07.159 --> 01:20:09.920
your crucial ligament or your achilles ten and gets more
1554
01:20:11.039 --> 01:20:15.600
interest than tearing axons in your brain. It's it's amazing
1555
01:20:15.640 --> 01:20:19.720
to me that there's more emphasis on orthopedic injuries than
1556
01:20:19.760 --> 01:20:20.479
brain injuries.
1557
01:20:20.640 --> 01:20:22.119
Yeah, I don't know why that is either. I think
1558
01:20:22.159 --> 01:20:28.720
the brain is mysterious enough that most people and many
1559
01:20:28.760 --> 01:20:31.399
clinicians just kind of back away with hands raised. But
1560
01:20:32.000 --> 01:20:34.880
if you are in the field of neurology or psychiatrist
1561
01:20:35.000 --> 01:20:37.399
bose it, then one has officially signed on to try
1562
01:20:37.439 --> 01:20:38.920
and resolve these matters.
1563
01:20:39.520 --> 01:20:40.600
So for somebody that.
1564
01:20:41.199 --> 01:20:45.079
Has a traumatic brain injury or low level concussion, excuse me,
1565
01:20:46.600 --> 01:20:51.079
would part of the primary advice be to try and
1566
01:20:51.119 --> 01:20:55.159
get one's sleep as good as possible be given that
1567
01:20:55.600 --> 01:21:00.680
sleep deprivation can compound traumatic brain injury ind deficits in
1568
01:21:00.760 --> 01:21:03.479
working memory, and who knows, maybe a good portion of
1569
01:21:03.520 --> 01:21:07.399
the deficits in working memory due to traumatic brain injury
1570
01:21:07.439 --> 01:21:09.880
and concussion is because of the sleep deprivation that it
1571
01:21:09.880 --> 01:21:10.319
can cause.
1572
01:21:10.359 --> 01:21:11.640
So it gets it can get circular.
1573
01:21:12.560 --> 01:21:15.399
Not only that, but one of the most common symptoms
1574
01:21:15.399 --> 01:21:17.880
that patients my patient with decussion have is is their
1575
01:21:18.000 --> 01:21:18.520
sleep is.
1576
01:21:18.479 --> 01:21:22.039
Disruptive, and that's true in neurology. It's fascinating.
1577
01:21:22.079 --> 01:21:25.680
Almost every neurological disorder, my patients complain of their sleep,
1578
01:21:25.720 --> 01:21:28.000
and and I started asking, you know, not a lot
1579
01:21:28.079 --> 01:21:31.119
of neurologists ask you how you're sleep, you know, but
1580
01:21:31.159 --> 01:21:33.079
I really I remember back for my regency, one of
1581
01:21:33.159 --> 01:21:35.439
the first things my attending would do when we got
1582
01:21:35.479 --> 01:21:35.960
to the ward.
1583
01:21:35.880 --> 01:21:38.159
Is that I just sleep last night. And it's just
1584
01:21:38.199 --> 01:21:39.319
across the board.
1585
01:21:39.560 --> 01:21:43.039
You know, patients are not falling asleep, they're not staying asleep,
1586
01:21:43.119 --> 01:21:45.800
and it's it's, uh, we still don't understand why just
1587
01:21:45.920 --> 01:21:49.319
brain injury does that. So almost every concussion patient says,
1588
01:21:49.319 --> 01:21:53.560
I'm not sleeping well, which then compounds, you know, compounds
1589
01:21:53.600 --> 01:21:58.760
the problem. So optimizing sleep obviously optimizing nutrition. There's a
1590
01:21:58.880 --> 01:22:01.920
question about activity. It used to be that we used
1591
01:22:01.920 --> 01:22:03.960
to recommend, you know, you had a concussion, you should
1592
01:22:04.119 --> 01:22:08.800
you should don't go to work, you know, sleep, you know,
1593
01:22:08.920 --> 01:22:11.000
just just take it easy for a while, don't.
1594
01:22:10.840 --> 01:22:12.800
Extra keep the blood strong.
1595
01:22:12.880 --> 01:22:15.000
But now it's it's it's the idea is that you
1596
01:22:15.039 --> 01:22:17.319
should really get up and moving as best you've got.
1597
01:22:17.600 --> 01:22:19.439
You got to do what you can tolerate. You don't
1598
01:22:19.439 --> 01:22:21.359
want to give yourself ahead. You don't want to give
1599
01:22:21.399 --> 01:22:23.920
yourself more of a headache or more light sensitivity, but
1600
01:22:24.039 --> 01:22:27.920
as much as you can tolerate. Is the thought these
1601
01:22:28.000 --> 01:22:31.479
days about sort of promoting recovery and then really getting
1602
01:22:31.479 --> 01:22:34.239
your brain back working. I think, you know a lot
1603
01:22:34.239 --> 01:22:36.000
of my patients they're off from work for a couple
1604
01:22:36.000 --> 01:22:38.199
of weeks and they feel fine, and they think they're
1605
01:22:38.199 --> 01:22:39.880
pretty much normal, and then the first day of work
1606
01:22:39.880 --> 01:22:44.119
as a complete disaster because until you actually test it
1607
01:22:44.119 --> 01:22:46.199
in real life, you don't know how what kind of
1608
01:22:46.199 --> 01:22:48.680
troubles you have. So I don't recommend going back full steam,
1609
01:22:48.720 --> 01:22:52.079
but I do recommend going back trying to build up
1610
01:22:52.119 --> 01:22:55.840
these these still skills again. And then I think we
1611
01:22:56.119 --> 01:22:58.039
you know, I think we need to develop therapies that
1612
01:22:58.079 --> 01:23:02.399
people will use, you know, things like goal management training,
1613
01:23:02.399 --> 01:23:05.880
which involves a therapist. And you know, health insurance doesn't
1614
01:23:06.039 --> 01:23:09.720
pay for this, so ninety nine percent of my patients
1615
01:23:09.800 --> 01:23:14.720
don't get any help, you know, by any kind of intervention, unfortunately.
1616
01:23:14.840 --> 01:23:19.560
But now we talked about technology, things like brain HQ.
1617
01:23:20.640 --> 01:23:24.000
Do you know about Braine HQ, so, Mike Mrzenik, which
1618
01:23:24.039 --> 01:23:29.880
I know you've talked about with with Eddy developed a
1619
01:23:29.920 --> 01:23:34.399
company called Positive Science where developed these brain training games
1620
01:23:34.520 --> 01:23:39.359
that can help I prove specific cognitive functions. And they're
1621
01:23:39.479 --> 01:23:42.479
very easy to do because they're online and they you know,
1622
01:23:42.600 --> 01:23:45.880
they're science behind them, and you can you can do
1623
01:23:45.920 --> 01:23:47.880
them so that in that way you don't have a
1624
01:23:47.920 --> 01:23:50.600
therapist in your room, but you can online sort of
1625
01:23:51.079 --> 01:23:54.640
do these sort of things that are targeting specific mechanisms,
1626
01:23:55.039 --> 01:23:56.840
trying to improve the kind of things that we think
1627
01:23:56.880 --> 01:23:59.760
are impaired by concussion. And I'd like to see more
1628
01:23:59.800 --> 01:24:02.000
pay since gets started on some of those things.
1629
01:24:02.119 --> 01:24:02.840
Accordaly, if you.
1630
01:24:02.840 --> 01:24:05.399
Go on the web and just say I'll do brain training,
1631
01:24:05.439 --> 01:24:07.800
you'll be overwhelmed with things and you don't know what
1632
01:24:07.880 --> 01:24:08.880
works and what doesn't work.
1633
01:24:08.960 --> 01:24:11.960
Yeah, I think the work that Merzenik and colleagues have done,
1634
01:24:11.960 --> 01:24:13.520
and we'll provide a link to that. I don't have
1635
01:24:13.560 --> 01:24:16.479
any financial stake in his in his work or products
1636
01:24:17.359 --> 01:24:20.479
trainings that is, but I will say I think Mike's
1637
01:24:20.600 --> 01:24:22.399
work has been tremendous.
1638
01:24:22.399 --> 01:24:24.439
I mean he is so far ahead of the curve.
1639
01:24:25.279 --> 01:24:29.239
Twenty years ago everyone was talking about neuroplasticity in critical periods.
1640
01:24:30.039 --> 01:24:31.840
They give a Nobel Prize to it to my scientific
1641
01:24:31.840 --> 01:24:36.319
great grandparents. David Hubie torn some weasel, and they deserve
1642
01:24:36.399 --> 01:24:39.560
that Nobel Prize. But there was a kind of central
1643
01:24:39.600 --> 01:24:42.039
tenet of neuroscience at that time was that critical period
1644
01:24:42.039 --> 01:24:45.680
plasticity ends around adolescents or one's early twenties, and that
1645
01:24:45.800 --> 01:24:48.600
is simply not true. And Mrzenic really, I think one
1646
01:24:48.640 --> 01:24:51.680
of the people who deserves credit for making it clear
1647
01:24:51.720 --> 01:24:56.960
that plasticity is ongoing. It takes some focus and work
1648
01:24:57.239 --> 01:24:59.760
to access it in adulthood, but that we can all
1649
01:24:59.800 --> 01:25:03.760
act access neuroplasticity, but it takes it's there. So I
1650
01:25:03.760 --> 01:25:05.600
don't know they should give Mrzenich a Nobel too, but
1651
01:25:05.640 --> 01:25:06.920
that you know, I'm not on the committee.
1652
01:25:06.960 --> 01:25:10.520
So just a little editorial there.
1653
01:25:12.239 --> 01:25:16.720
The description of specific cognitive trainings that can improve working
1654
01:25:16.760 --> 01:25:19.880
memory in people that have had traumatic brain injury or concussion,
1655
01:25:20.720 --> 01:25:24.000
as well as our earlier discussion about the development of
1656
01:25:24.079 --> 01:25:27.760
frontal lobe function and plasticity a frontal load function makes
1657
01:25:27.760 --> 01:25:33.079
me wonder is the working memory circuitry and frontal lobe
1658
01:25:33.079 --> 01:25:35.560
function a use it or lose it kind of circuit,
1659
01:25:35.880 --> 01:25:39.840
Meaning if somebody you know goes to high school, graduates
1660
01:25:39.880 --> 01:25:42.800
high school, and then gets into a lifestyle or a college,
1661
01:25:42.840 --> 01:25:45.039
and then graduates college as well, and then gets into
1662
01:25:45.079 --> 01:25:48.359
a lifestyle where they're not reading very many books. They're
1663
01:25:48.399 --> 01:25:52.079
definitely scrolling social media. They're carrying out their daily tasks
1664
01:25:52.119 --> 01:25:58.159
with you know, apparently high degree of functionality, but they're
1665
01:25:58.159 --> 01:26:02.720
not really pushing the four brain circuits. Do we imagine
1666
01:26:02.760 --> 01:26:06.880
that some of those four brain circuits regress aka use
1667
01:26:06.920 --> 01:26:10.199
it or lose it? It seems to me that a
1668
01:26:10.199 --> 01:26:12.359
few years back, maybe ten fifteen years back, there was
1669
01:26:12.359 --> 01:26:13.880
a lot of interest in, you know, how to maintain
1670
01:26:13.880 --> 01:26:15.840
cognitive function. In fact, one of the most common questions
1671
01:26:15.840 --> 01:26:19.119
I would get, even as a neuroscientist primarily focused on
1672
01:26:19.159 --> 01:26:21.720
the visual and autonomic nervous system, was how do I
1673
01:26:21.800 --> 01:26:24.039
keep my memory as I age? It seems to me
1674
01:26:24.119 --> 01:26:27.239
that training it up and then continuing to use those
1675
01:26:27.239 --> 01:26:29.920
circuits as would be a really good way reading books
1676
01:26:30.159 --> 01:26:34.119
without forcing oneself to finish the chapter, even though distractions
1677
01:26:34.199 --> 01:26:37.760
jump into one's head things like that. For me, it's
1678
01:26:37.840 --> 01:26:39.159
when I go to the gym, I try not to
1679
01:26:39.159 --> 01:26:40.760
bring my phone, and if I do, all listen to
1680
01:26:40.800 --> 01:26:42.239
one album of music.
1681
01:26:42.239 --> 01:26:43.960
But I won't allow myself to play on my phone.
1682
01:26:43.960 --> 01:26:44.479
I try.
1683
01:26:45.159 --> 01:26:48.399
I mean not interrupting a conversation with text messaging. I
1684
01:26:48.399 --> 01:26:52.199
mean basically the landscape I'm trying to draw here is
1685
01:26:52.439 --> 01:26:56.079
it seems like the world is designed to disrupt that.
1686
01:26:56.119 --> 01:26:59.159
The modern world is designed to disrupt working memory and
1687
01:26:59.159 --> 01:27:03.359
cognition of the loans, right, And we need to do
1688
01:27:03.399 --> 01:27:07.119
some real training, just like muscles and atrophy and cardiac
1689
01:27:07.199 --> 01:27:10.479
fitness atrophies. If we're not doing readier you resistance in
1690
01:27:10.479 --> 01:27:11.720
cardiovascular training.
1691
01:27:12.279 --> 01:27:12.680
Is that?
1692
01:27:12.880 --> 01:27:13.039
Yeah?
1693
01:27:13.079 --> 01:27:13.800
I think that's fair.
1694
01:27:13.880 --> 01:27:16.680
I think you know, of all the systems that decline
1695
01:27:16.720 --> 01:27:20.079
with aging, not every brain system declines, but certainly the
1696
01:27:20.159 --> 01:27:22.680
frontal executive system we're talking about is one that takes
1697
01:27:22.720 --> 01:27:24.279
more of a decline than others.
1698
01:27:24.279 --> 01:27:26.760
That's just how it is with with healthy aging.
1699
01:27:27.800 --> 01:27:31.359
Not surprising, it's it's the most complicated system, and it's
1700
01:27:31.399 --> 01:27:34.640
probably the most biologically costly, and so you know, the
1701
01:27:34.680 --> 01:27:37.800
more complicated system is going to take more of a
1702
01:27:37.880 --> 01:27:42.359
hit than than other systems. And so certainly, I don't
1703
01:27:42.359 --> 01:27:46.479
know about regressing, but certainly we're not maybe accelerating this
1704
01:27:46.479 --> 01:27:50.119
this this decline that we know exists. And but the
1705
01:27:50.119 --> 01:27:52.319
way I would think about it though, is that not
1706
01:27:52.439 --> 01:27:56.159
just trying to prevent a decline. But what we talked
1707
01:27:56.159 --> 01:28:00.319
about before, there's no reason not to optimize if everything
1708
01:28:00.439 --> 01:28:02.279
is couched. And I don't want to get dementia, and
1709
01:28:02.279 --> 01:28:04.119
I don't want to get Alzheimer's disease, and I don't
1710
01:28:04.159 --> 01:28:06.359
want to get this in that, I think that's not
1711
01:28:06.399 --> 01:28:07.840
the way we should be looking about it. We want
1712
01:28:07.880 --> 01:28:13.520
to look about optimizing health and brain health and getting
1713
01:28:13.600 --> 01:28:16.880
up to our optimal levels, because otherwise we're always playing
1714
01:28:16.880 --> 01:28:19.840
defense instead of playing playing offense. And that's really hard
1715
01:28:19.880 --> 01:28:23.319
for neurologists. We have a hard time thinking about brain health.
1716
01:28:23.399 --> 01:28:26.359
Even though we're the brain specialists. We think about brain disease,
1717
01:28:27.119 --> 01:28:29.560
and we're just now as a field start thinking about
1718
01:28:29.600 --> 01:28:33.199
preventative neurology, which seems and thinking about it not just
1719
01:28:33.279 --> 01:28:37.960
like stopping Alzheimer's disease, but promoting healthy health and a
1720
01:28:37.960 --> 01:28:41.159
healthy brain. Neure just you know, neural just don't talk
1721
01:28:41.239 --> 01:28:45.279
to patients about sort of healthy patients about being healthier.
1722
01:28:46.560 --> 01:28:49.119
I love how candid you are about the medical profession,
1723
01:28:50.039 --> 01:28:52.880
and I like to think it's changing. Something happened in
1724
01:28:53.000 --> 01:28:57.439
the twenty twenty twenty twenty one ear. I think I
1725
01:28:57.560 --> 01:29:01.239
feel it's just my bias, But I feel that the
1726
01:29:01.319 --> 01:29:04.880
general public started becoming more aware of the things they
1727
01:29:04.960 --> 01:29:08.359
might do to support their mental and physical health. Maybe
1728
01:29:08.399 --> 01:29:10.119
they had more time on their hands, but I think
1729
01:29:10.119 --> 01:29:13.960
there was just more foraging for information. I love the
1730
01:29:14.000 --> 01:29:18.800
idea that through simple practices like forcing oneself to read
1731
01:29:18.840 --> 01:29:21.960
a book chapter start to finish without looking at one's phone,
1732
01:29:22.640 --> 01:29:24.880
even if it takes twice as long as one would like,
1733
01:29:26.239 --> 01:29:29.640
redirecting one's focus when what focus moves away is it's
1734
01:29:29.640 --> 01:29:33.760
a way of keeping working memory and cognitive function online,
1735
01:29:33.800 --> 01:29:38.079
maybe even strengthening it, as you said, optimizing it. You know,
1736
01:29:38.119 --> 01:29:42.800
I think that there's so much emphasis now on physical health,
1737
01:29:42.840 --> 01:29:45.520
which I think is great sleep thanks to Matt Walker,
1738
01:29:45.560 --> 01:29:47.640
you know, he really you know, brought that torch in
1739
01:29:47.720 --> 01:29:51.760
on sleep, and now others like myself are really you know,
1740
01:29:51.800 --> 01:29:54.159
trying to amplify the message or the critical role of sleep.
1741
01:29:54.159 --> 01:29:56.960
But also, you know, most people realize they should probably
1742
01:29:57.000 --> 01:29:59.880
at least walk, as you know, the ten thousand steps
1743
01:30:00.000 --> 01:30:02.800
thing is not a bad idea. Getting some heart rate
1744
01:30:02.880 --> 01:30:05.039
up a few times a week or more, maybe doing
1745
01:30:05.039 --> 01:30:06.840
some resistance training a few times a week or more
1746
01:30:06.880 --> 01:30:10.039
and then and not just for athletes, but for elderly folks,
1747
01:30:10.039 --> 01:30:13.720
men and women. You know, I feel like we need
1748
01:30:13.720 --> 01:30:19.399
the same for cognition for brain function, and there just
1749
01:30:19.439 --> 01:30:22.720
isn't a structure to that. No one can say right now,
1750
01:30:22.760 --> 01:30:25.279
you know, you need to do three chapters of reading
1751
01:30:25.880 --> 01:30:28.960
you know, fiction per week, or you've got to read
1752
01:30:29.000 --> 01:30:31.279
a you got to learn a few new vocabulary words
1753
01:30:31.279 --> 01:30:33.680
and then write sentences with them they do in school.
1754
01:30:34.159 --> 01:30:37.119
But then we're just you know, set into the general
1755
01:30:37.159 --> 01:30:41.800
population and right and most people I think, regress right now.
1756
01:30:42.079 --> 01:30:45.640
Yeah, I mean, I think the big problem with brain
1757
01:30:45.680 --> 01:30:48.600
health is trying to have a measure of what brain
1758
01:30:48.680 --> 01:30:51.760
health is. And it's interesting to me, again as a
1759
01:30:51.800 --> 01:30:55.720
physician thinking about it from a urologists standpoint.
1760
01:30:56.640 --> 01:30:59.760
When you go to your family doctor, your primary care.
1761
01:30:59.600 --> 01:31:04.039
Physician, and every year from your yearly physical, uh, they
1762
01:31:04.119 --> 01:31:08.800
examine every organ in your body except your brain, your lungs,
1763
01:31:09.039 --> 01:31:12.720
your heart, your skulp system, your skin. But what what
1764
01:31:12.960 --> 01:31:15.159
do they do for you, you know, outside of having
1765
01:31:15.159 --> 01:31:18.760
a conversation with you and no cognitive test, there's nothing memory.
1766
01:31:18.920 --> 01:31:21.119
They don't measure your brain at all.
1767
01:31:21.199 --> 01:31:22.560
And it's not their fault there.
1768
01:31:22.960 --> 01:31:25.600
We haven't provided the field has not provided them with
1769
01:31:25.680 --> 01:31:28.920
a test of brain health. And so part of the
1770
01:31:28.920 --> 01:31:31.119
problem is we don't have a measurement of brain health.
1771
01:31:31.319 --> 01:31:34.239
I'm involved and it's something called the Brain Health Project,
1772
01:31:34.279 --> 01:31:37.239
which is at UT Dallas, which is their goal as
1773
01:31:37.279 --> 01:31:41.479
a study h to enroll one hundred thousand people in
1774
01:31:41.880 --> 01:31:45.720
UH and they've been developing a brain health index. And
1775
01:31:46.560 --> 01:31:49.520
that's a complicated thing to do, but I really believe
1776
01:31:49.560 --> 01:31:52.479
they're onto something because it's not just cognition. It's cognition,
1777
01:31:52.640 --> 01:31:58.039
it's it's social, it's it's lifestyle like sleep, and it's it's.
1778
01:31:58.199 --> 01:31:59.600
Well being the brain.
1779
01:31:59.640 --> 01:32:01.920
A brain health index is going to cover all of
1780
01:32:01.960 --> 01:32:03.119
these aspects.
1781
01:32:03.159 --> 01:32:04.520
So they've developed.
1782
01:32:04.159 --> 01:32:09.119
Quite an interesting UH important index which which can which
1783
01:32:09.199 --> 01:32:11.720
does try to capture all aspects of brain health and
1784
01:32:11.760 --> 01:32:15.279
then can be used to track UH where you can
1785
01:32:15.319 --> 01:32:17.319
track your brain health over time with.
1786
01:32:17.399 --> 01:32:20.520
Interventions that they've they've developed. So we need.
1787
01:32:20.319 --> 01:32:22.800
Something like we need to first once we develop a
1788
01:32:22.880 --> 01:32:25.960
brain health index, that's that then then we have something
1789
01:32:26.000 --> 01:32:29.359
to to follow and and to be able to measure
1790
01:32:29.640 --> 01:32:32.359
if if we are optimizing our brain health. Otherwise, how
1791
01:32:32.399 --> 01:32:35.039
do you know if you're you're optimizing your your brain health.
1792
01:32:35.079 --> 01:32:37.039
You don't your doctor's not telling you.
1793
01:32:37.039 --> 01:32:37.600
You don't know.
1794
01:32:38.800 --> 01:32:40.680
All these games you get on in the web don't
1795
01:32:40.720 --> 01:32:44.199
really tell you. So when we develop that, uh, then
1796
01:32:44.359 --> 01:32:46.640
all of the things that can promote brain health will
1797
01:32:46.640 --> 01:32:48.560
be measurable, and I think it will take off the
1798
01:32:48.600 --> 01:32:50.359
way physical fitness did.
1799
01:32:51.399 --> 01:32:54.039
Perhaps you get enough of it from your work. But
1800
01:32:54.319 --> 01:32:57.039
given what you know about brain health and approaches to
1801
01:32:57.079 --> 01:32:58.960
brain health, what are some of the things that you
1802
01:32:59.079 --> 01:33:06.520
do i'd sleep, exercise, nutrition in terms of trying to
1803
01:33:06.560 --> 01:33:08.720
optimize brain function. I mean, do you make it a
1804
01:33:08.760 --> 01:33:10.520
point to read fiction. Do you make it a point
1805
01:33:10.560 --> 01:33:14.880
to learn new skills, like instruments, things like that. Again,
1806
01:33:14.920 --> 01:33:17.840
maybe your profession and your personal life keeps you busy
1807
01:33:17.920 --> 01:33:20.000
enough that you don't have to do those things. I mean,
1808
01:33:20.039 --> 01:33:24.319
for me, gathering, organizing and disseminating the information for the
1809
01:33:24.359 --> 01:33:28.039
podcast feels like the heavy lifting mental work for me.
1810
01:33:28.119 --> 01:33:30.279
But I'm keenly aware of the.
1811
01:33:30.199 --> 01:33:34.119
Fact that were I to read more fiction or learn
1812
01:33:34.159 --> 01:33:37.479
an instrument, I mean, everyone else around me would suffer
1813
01:33:37.520 --> 01:33:40.720
if I learned an instrument, but that it would probably
1814
01:33:40.720 --> 01:33:43.000
benefit me in some real way. What are the things
1815
01:33:43.000 --> 01:33:45.640
that you do and that you think are kind of
1816
01:33:45.720 --> 01:33:48.680
access points that hopefully people also enjoy.
1817
01:33:49.680 --> 01:33:51.439
Yeah, no, I agree with that.
1818
01:33:51.680 --> 01:33:55.079
I think when you have a busy career and you're
1819
01:33:55.079 --> 01:33:58.279
doing many different things like teaching and research and seeing patients,
1820
01:33:58.279 --> 01:33:59.239
I've always felt.
1821
01:33:59.039 --> 01:34:02.079
That I I'm.
1822
01:34:00.319 --> 01:34:03.680
Maxing out on I'm full. My executive function is being
1823
01:34:03.720 --> 01:34:04.520
tested to the limit.
1824
01:34:04.560 --> 01:34:06.560
But you're like an athlete, You're like a professional athlete
1825
01:34:06.600 --> 01:34:07.079
of the mind.
1826
01:34:07.359 --> 01:34:08.439
Yeah, in a way.
1827
01:34:08.520 --> 01:34:11.920
But then then you realize there's that's that's not you know,
1828
01:34:11.960 --> 01:34:15.840
that's not everything there there's so many other aspects everything
1829
01:34:15.960 --> 01:34:18.000
mn's from the brain. So you start to think about
1830
01:34:18.000 --> 01:34:20.760
what should I be doing in my my life as
1831
01:34:20.880 --> 01:34:23.640
as a father and a husband, what what what should
1832
01:34:23.680 --> 01:34:25.720
I be doing, you know, in terms of promoting social
1833
01:34:25.720 --> 01:34:29.399
interactions with friends and and what should I be doing
1834
01:34:29.399 --> 01:34:33.199
for sleep and health of sleep and nutrition? And it's
1835
01:34:33.199 --> 01:34:35.119
funny you bring up books. I think you know, I
1836
01:34:35.119 --> 01:34:38.239
went probably twenty years where I never read any non
1837
01:34:38.439 --> 01:34:41.159
you know, any fictional book, and said this, this can't
1838
01:34:41.159 --> 01:34:44.520
be good for my brain, and then just consciously started
1839
01:34:44.680 --> 01:34:49.199
you know, reading reading books and reading His and more
1840
01:34:49.239 --> 01:34:52.000
nonfiction books and just listening to books or reading reading.
1841
01:34:52.159 --> 01:34:55.359
Yeah. I still like to read the hard, hardcovers, you know, likewise.
1842
01:34:55.520 --> 01:34:58.840
Unfortunately, when I was an undergraduate, you know, with PREMD,
1843
01:34:58.880 --> 01:35:01.079
they don't let you take any horses that are interesting.
1844
01:35:01.119 --> 01:35:03.159
So I never learned any history or or you know,
1845
01:35:03.199 --> 01:35:05.079
all the books that I never read. I started reading
1846
01:35:05.119 --> 01:35:07.439
my kids, you know, English literature books that I never
1847
01:35:07.439 --> 01:35:09.960
got a chance to, and started reading history. And so yeah,
1848
01:35:09.960 --> 01:35:12.840
I always felt just like just increasing you know, just
1849
01:35:12.960 --> 01:35:15.039
knowledge was was another you know, like I said, our
1850
01:35:15.039 --> 01:35:17.880
brain just stores information. That's one of his jobs, so
1851
01:35:17.920 --> 01:35:21.439
that that's got to be useful. But but again, all
1852
01:35:21.479 --> 01:35:24.640
of these things that I do believe help brain health,
1853
01:35:25.600 --> 01:35:28.119
we need we need some way to measure it.
1854
01:35:28.199 --> 01:35:31.039
I think certainly, if you feel healthy.
1855
01:35:30.760 --> 01:35:33.640
That's an important thing. If you feel like you're healthy
1856
01:35:33.680 --> 01:35:36.960
physically or mentally, that's that's good. That's a good start.
1857
01:35:37.239 --> 01:35:39.119
But if we actually had a way to sort of
1858
01:35:39.159 --> 01:35:41.239
track it the way we can track you know, heart
1859
01:35:41.319 --> 01:35:45.199
disease and lung disease and skin and things like that,
1860
01:35:45.279 --> 01:35:47.960
I think that would really boost everyone's confidence that this
1861
01:35:48.119 --> 01:35:50.720
is really making a making a difference.
1862
01:35:51.359 --> 01:35:53.720
Well, on the basis of today's conversation, I'm going to
1863
01:35:53.920 --> 01:35:57.600
read some fiction. I read a lot of nonfiction, and
1864
01:35:57.640 --> 01:36:00.640
I enjoyed I listened to some audiobooks, but I I
1865
01:36:00.760 --> 01:36:04.640
just it's crazy to me because I'm a neuroscientist by training,
1866
01:36:04.760 --> 01:36:09.800
and I understand neuroplasticity, and I do know a bit
1867
01:36:09.880 --> 01:36:13.560
about fitness and the key role of remaining active kind
1868
01:36:13.560 --> 01:36:16.279
of use it or lose it and maybe improve it. Right,
1869
01:36:16.359 --> 01:36:20.920
kind of that wasn't intended to rhyme folks kind of behaviors,
1870
01:36:20.960 --> 01:36:24.279
but clearly, based on everything you've told us that if
1871
01:36:24.319 --> 01:36:28.520
we don't exercise these working memory and other circuits for cognition,
1872
01:36:28.680 --> 01:36:32.039
like why should they stick around? And I'm beginning to
1873
01:36:32.079 --> 01:36:35.399
think that social media as entertaining as it is, and
1874
01:36:35.479 --> 01:36:39.039
I learned there and I teach there, but that it's
1875
01:36:39.119 --> 01:36:45.520
not a cohesive plot, right, It's like those baby otters,
1876
01:36:46.680 --> 01:36:49.119
that really cool looking dog that I'd love to own.
1877
01:36:49.159 --> 01:36:53.239
I'm thinking about geting another dog. This interesting conference. You know,
1878
01:36:53.399 --> 01:36:57.439
it's like random pseudo orandom tailored to me, of course,
1879
01:36:57.439 --> 01:36:58.840
because that's what their algorithms do.
1880
01:36:58.960 --> 01:37:01.760
But that's not following a plot.
1881
01:37:02.039 --> 01:37:09.760
Character development, antagonist, protagonists, uh, any of the things that
1882
01:37:09.800 --> 01:37:13.520
provide like cognitive richness. It's kind of obvious as I
1883
01:37:13.600 --> 01:37:17.199
as I say this, but I feel like we're divorced
1884
01:37:17.239 --> 01:37:21.119
from these things that really helped evolve culture and involved individuals.
1885
01:37:21.600 --> 01:37:25.359
And it takes some discipline. But like a run or
1886
01:37:25.399 --> 01:37:27.079
going to the gym, you do a few times for
1887
01:37:27.439 --> 01:37:29.439
shorter amount of time with less intensity and prey soon
1888
01:37:29.520 --> 01:37:31.760
you're up to speed and there's an upper threshold. Unless
1889
01:37:31.760 --> 01:37:33.560
you're going to be a pro I'm not. I'm certainly
1890
01:37:33.560 --> 01:37:36.600
not gonna be an English lit I mean, you know, professor, you.
1891
01:37:36.560 --> 01:37:39.880
Know so, I don't think obviously boosting execs function is
1892
01:37:39.880 --> 01:37:41.960
incredibly important. But I don't think it's gonna happen just
1893
01:37:42.000 --> 01:37:45.399
with technology. I think it's gonna need it needs human interaction.
1894
01:37:45.720 --> 01:37:48.279
I mean, I I believe execution FUNC should be taught
1895
01:37:48.319 --> 01:37:51.279
in you know school as one of the court, you know,
1896
01:37:51.359 --> 01:37:55.159
as as a course. Uh, this school management theory that
1897
01:37:55.199 --> 01:37:57.560
I talk about could be taught in school. It's what
1898
01:37:57.640 --> 01:37:59.319
you do with your students. For example, when you have
1899
01:37:59.319 --> 01:38:02.800
a graduate students and they have to learn how to
1900
01:38:02.880 --> 01:38:06.479
read the literature and design experiment and carry out the experiment.
1901
01:38:07.239 --> 01:38:09.640
There's no technology that's going to just be able to
1902
01:38:09.680 --> 01:38:11.680
teach them how to do that. You've got to intervene
1903
01:38:11.680 --> 01:38:14.960
sometimes and say stop reading all those papers. That are
1904
01:38:15.000 --> 01:38:18.359
not relevant, okay, or you know, you're you're you've piloted
1905
01:38:18.399 --> 01:38:21.520
this enough, get going. It's it's that kind of wisdom
1906
01:38:21.600 --> 01:38:23.520
that that that you get when you get older, that
1907
01:38:23.520 --> 01:38:27.000
that that that allows that has to be uh has
1908
01:38:27.039 --> 01:38:30.159
to be on top of the technology. So that's why
1909
01:38:30.239 --> 01:38:33.479
I think we also need to it needs to be directed.
1910
01:38:33.560 --> 01:38:36.560
So whether it's in school or whether it's.
1911
01:38:36.479 --> 01:38:38.840
In a patient, I think there still needs to be
1912
01:38:39.000 --> 01:38:42.279
someone coaching us, you know, And I know that's why
1913
01:38:42.479 --> 01:38:45.279
life coaches have have been some people have really benefited
1914
01:38:45.319 --> 01:38:48.319
from life coaches because someone just needs It sounds obvious
1915
01:38:48.359 --> 01:38:51.199
when you tell your kids, you know, just write, you know,
1916
01:38:51.399 --> 01:38:53.520
just just do it this way, you know, break it
1917
01:38:53.640 --> 01:38:54.600
up into little pieces.
1918
01:38:54.640 --> 01:38:55.720
It seems so obvious.
1919
01:38:55.760 --> 01:38:57.880
But to them it's not always obvious, and they just
1920
01:38:57.920 --> 01:39:00.399
need to be told something simple for it to make
1921
01:39:00.439 --> 01:39:01.199
a big difference.
1922
01:39:01.520 --> 01:39:03.760
And in school, we were we were brought along step
1923
01:39:03.800 --> 01:39:06.199
by step and there was context. So why wouldn't it
1924
01:39:06.239 --> 01:39:09.720
be the same in adulthood. I'm realizing I shed probably
1925
01:39:09.760 --> 01:39:12.319
learn how to play chess. Yeah, it seems like a
1926
01:39:12.359 --> 01:39:13.039
good game.
1927
01:39:12.920 --> 01:39:15.680
Right, Chess is yeah, any any one.
1928
01:39:15.560 --> 01:39:18.680
Of the working memory, you got to keep information online.
1929
01:39:18.720 --> 01:39:22.880
There's sure there's a bunch else there, I think, but
1930
01:39:23.000 --> 01:39:26.279
as a tool to improve cognition, I was also thinking,
1931
01:39:26.319 --> 01:39:28.840
you know, some people orient more towards the arts. My
1932
01:39:28.920 --> 01:39:32.560
sister is really great about and she's a therapist in
1933
01:39:32.600 --> 01:39:35.560
San Francisco. But also it takes like theater classes, and
1934
01:39:35.600 --> 01:39:37.600
she said, you know, like improv is like forces you
1935
01:39:37.640 --> 01:39:40.760
to keep on your toes, keep the context there. You're
1936
01:39:40.840 --> 01:39:43.159
up on your feet, like you know. And I wasn't
1937
01:39:43.159 --> 01:39:45.159
a theater kid. I did the crew. I did like
1938
01:39:45.199 --> 01:39:47.239
the pulling the curtains and stuff to like, went and
1939
01:39:47.239 --> 01:39:50.560
did other things. But but but that whole biz is
1940
01:39:50.600 --> 01:39:54.960
about being you know, learning the novel rules set in
1941
01:39:55.000 --> 01:39:55.399
the moment.
1942
01:39:55.920 --> 01:39:58.800
You know, it's improv by definition absolutely.
1943
01:39:58.840 --> 01:40:01.720
I mean anything that requires you to have that you know,
1944
01:40:02.039 --> 01:40:03.760
where there's a goal and you've got to break it
1945
01:40:03.800 --> 01:40:06.520
down to sub goals, and you've got to do it simultaneously,
1946
01:40:06.560 --> 01:40:09.119
and you've got to filter out distractions and you know,
1947
01:40:10.039 --> 01:40:12.199
you know, for example, my kids got me one of
1948
01:40:12.239 --> 01:40:16.840
these pizza ovens for Christmas, and you know how you
1949
01:40:16.880 --> 01:40:18.920
think it's easy just sort of make some pizza and
1950
01:40:18.960 --> 01:40:21.000
throw it in the oven and done. That's where I'm
1951
01:40:21.039 --> 01:40:23.319
on my third time and it's still not even round.
1952
01:40:24.920 --> 01:40:27.239
I'll come over and test. That sounds good.
1953
01:40:27.640 --> 01:40:30.399
That sounds good, and you're in a city with great food,
1954
01:40:30.479 --> 01:40:34.479
so the standard is really high. Attempted to make a
1955
01:40:34.479 --> 01:40:36.720
reference to the cheeseboard pizza, but I want to keep
1956
01:40:36.720 --> 01:40:39.319
the lines as short as possible because they're already too long.
1957
01:40:41.960 --> 01:40:44.399
Maybe we could talk a little bit about some other
1958
01:40:44.720 --> 01:40:51.279
unfortunately common disease states, Parkinson's and Alzheimer's. Let's start with Alzheimer's.
1959
01:40:51.600 --> 01:40:56.520
I think a few things scare people more than the
1960
01:40:56.560 --> 01:40:59.199
idea of getting Alzheimer's, especially if they have Alzheimer's in
1961
01:40:59.239 --> 01:41:01.680
their family. First of all, what is the genetic link
1962
01:41:01.720 --> 01:41:03.960
with Alzheimer's. If one has a parent or grandparent that
1963
01:41:04.039 --> 01:41:09.079
got Alzheimer's, is there a known increase in their one's
1964
01:41:09.199 --> 01:41:10.680
risk for getting Alzheimer's.
1965
01:41:11.079 --> 01:41:14.199
It's not that straightforward as other diseases. There's disease like
1966
01:41:14.279 --> 01:41:17.000
hunting disease, where it's a very strong link that if
1967
01:41:17.039 --> 01:41:20.039
you have a parent you have a very high chance
1968
01:41:20.039 --> 01:41:23.000
of getting it. But there's so many factors that it's
1969
01:41:23.039 --> 01:41:24.520
not necessarily case.
1970
01:41:24.359 --> 01:41:27.399
That increases your risk of getting it.
1971
01:41:27.399 --> 01:41:31.000
There are families where there is something special about the family,
1972
01:41:31.039 --> 01:41:32.600
where it just runs in families.
1973
01:41:32.680 --> 01:41:34.119
But I try to.
1974
01:41:35.760 --> 01:41:41.760
Not scare my patient's children into worrying that they're necessarily
1975
01:41:41.760 --> 01:41:44.920
going to get Alzheimer's, because it's not that straightforward.
1976
01:41:45.960 --> 01:41:50.359
As I understand, Alzheimer's is the NERD's gener disorder impacts
1977
01:41:50.399 --> 01:41:52.640
the hippocampus, among other structures.
1978
01:41:53.000 --> 01:41:54.159
There's been some debate in.
1979
01:41:54.119 --> 01:41:56.279
Recent years as to whether or not the whole amyloid
1980
01:41:56.359 --> 01:42:01.279
hypothesis is real or not. There's a bunch of unfortunately
1981
01:42:01.760 --> 01:42:06.720
false data, accusations and that whole thing. But my understanding
1982
01:42:06.800 --> 01:42:08.479
is that if you look at a slice of human
1983
01:42:08.479 --> 01:42:13.119
brain from an a patient that died with Alzheimer's, maybe
1984
01:42:13.159 --> 01:42:16.680
even from Alzheimer's, that you see plaques and tangles, you
1985
01:42:16.720 --> 01:42:23.880
see these subsellar structures and build up, and that our
1986
01:42:23.920 --> 01:42:26.279
basic understanding of Alzheimer's that's in the textbook and that
1987
01:42:26.319 --> 01:42:30.920
most people have heard of is still correct. Right, Yes, okay,
1988
01:42:31.000 --> 01:42:34.880
because I think a couple of years ago it was. Unfortunately,
1989
01:42:34.960 --> 01:42:36.920
the way social media sometimes can work is that, you know,
1990
01:42:36.960 --> 01:42:38.920
the idea was that it was all wrong, right, you know,
1991
01:42:39.000 --> 01:42:41.800
all wrong, and indeed somebody fudged data, they made up
1992
01:42:41.840 --> 01:42:47.079
data and that's terrible. But Alzheimer's is anergic genertive disorder
1993
01:42:47.399 --> 01:42:51.119
includes the hippocampus. Plaques and tangles are present in the neurons.
1994
01:42:51.119 --> 01:42:53.760
Those are not good for neurons, as I understand. So
1995
01:42:54.199 --> 01:42:56.680
what's the controversy like and why don't we have a
1996
01:42:56.760 --> 01:43:00.000
treatment for Alzheimer's yet? I feel like almost every other
1997
01:43:00.000 --> 01:43:03.199
psychiatric disease, including Parkinson's, like, there's certain things you can
1998
01:43:03.279 --> 01:43:05.239
do to at least push the system in the right way.
1999
01:43:05.840 --> 01:43:10.199
Why is Alzheimer's and other dementia so tricky?
2000
01:43:11.039 --> 01:43:14.720
Yeah, I mean it's very frustrating because the neuroggener source.
2001
01:43:14.760 --> 01:43:18.840
It's just it's so so many factors that are probably
2002
01:43:18.880 --> 01:43:22.279
involved in the pathology that there's not once you know
2003
01:43:22.399 --> 01:43:27.000
one single transmitter. The Parkin's disease, it's a decreased dope mean,
2004
01:43:27.079 --> 01:43:30.039
and so one transmitter can make a very big difference.
2005
01:43:30.840 --> 01:43:32.960
Early on in Alzheimer's it was discovered that there was
2006
01:43:33.039 --> 01:43:36.359
low acyl coline in the brains, and the only approved
2007
01:43:37.199 --> 01:43:40.720
treatment for Alzheimer's disease is a drug that boosts acyl coline.
2008
01:43:40.840 --> 01:43:43.439
What's the drug, right, It's called the nepazil. There's a
2009
01:43:43.439 --> 01:43:47.479
few of them. They're anti coolon estraates inhibitors that boost astylcholine.
2010
01:43:47.840 --> 01:43:50.079
They've been around for twenty years or more.
2011
01:43:50.680 --> 01:43:52.119
And you know the reality.
2012
01:43:51.760 --> 01:43:53.640
Is when you give it to your patients, they don't
2013
01:43:53.840 --> 01:43:58.079
see much of a difference because it's not the primary deficits.
2014
01:43:58.119 --> 01:44:00.560
So the real problem has been trying and find out
2015
01:44:00.600 --> 01:44:02.119
what is the primary.
2016
01:44:01.840 --> 01:44:03.640
Mechanism that's leading to this.
2017
01:44:05.000 --> 01:44:08.319
The wide range of cognitive behavioral issues, and there doesn't
2018
01:44:08.359 --> 01:44:11.000
seem to be at least one transmitter that can make
2019
01:44:11.039 --> 01:44:12.920
the difference. And so now the push has been is
2020
01:44:12.960 --> 01:44:15.760
there one Is there something else that we can do?
2021
01:44:15.600 --> 01:44:19.039
We can we block amyloid, can we block something in
2022
01:44:19.079 --> 01:44:22.840
the pathology, And again it just has not been successful.
2023
01:44:23.119 --> 01:44:25.920
It's very frustrating because I think it was over probably
2024
01:44:25.920 --> 01:44:28.439
thirty five years ago. I saw my first Alzheimer's patients,
2025
01:44:28.479 --> 01:44:32.560
and I don't believe I say that much different to
2026
01:44:32.680 --> 01:44:34.920
them now, you know, except that we have a lot
2027
01:44:34.960 --> 01:44:37.159
more things we can do just on the social side
2028
01:44:37.199 --> 01:44:39.600
of things. But unfortunately for drugs, we don't have anything
2029
01:44:39.840 --> 01:44:44.520
that's been really transformative. But again, that that's I think
2030
01:44:44.560 --> 01:44:47.840
part of being a neurologi is it sounds very depressing.
2031
01:44:47.880 --> 01:44:50.239
But I think part of the what the family isn't
2032
01:44:50.279 --> 01:44:51.199
always looking.
2033
01:44:51.039 --> 01:44:51.640
For a cure.
2034
01:44:51.720 --> 01:44:53.960
Of course, that's they'd like to have a cure, but
2035
01:44:54.039 --> 01:44:57.399
I think them understanding what's going on, what to expect,
2036
01:44:57.520 --> 01:44:59.920
how to handle the behaviors is what they're really app
2037
01:45:00.279 --> 01:45:02.399
at least until we find, you know, a cure.
2038
01:45:03.159 --> 01:45:07.239
Parkinson's you mentioned is a deficit in dopaminergic function due
2039
01:45:07.760 --> 01:45:12.960
largely to degeneration of dopaminergic neurons. There there's some some
2040
01:45:13.039 --> 01:45:17.520
effective treatments, right el dopa. Did you know there's this
2041
01:45:17.640 --> 01:45:20.079
over the counter stuff that's sold that a lot of
2042
01:45:20.119 --> 01:45:22.680
people take who don't have Parkinson's. I'm not suggesting they
2043
01:45:22.680 --> 01:45:26.479
take it, called mcuna pruines. It's the velvety bean.
2044
01:45:26.720 --> 01:45:29.840
Yeah, I've heard of it. It's dopa, however, Yeah.
2045
01:45:29.640 --> 01:45:32.239
It's in present in like some energy drinks and supplements,
2046
01:45:32.279 --> 01:45:34.159
and people can go buy it. I'm not suggesting they
2047
01:45:34.159 --> 01:45:39.680
do that. I actually tried it. Boy, feel being really
2048
01:45:39.720 --> 01:45:43.199
dopamined out does not to me doesn't feel that good. Yeah,
2049
01:45:43.239 --> 01:45:45.560
I felt kind of agitated, my vision got a little,
2050
01:45:45.960 --> 01:45:49.439
you know, twinkly. It did not feel like a high
2051
01:45:49.520 --> 01:45:51.560
of any kind. And then I felt lousy for a
2052
01:45:51.560 --> 01:45:52.960
couple hours after it wore off.
2053
01:45:53.279 --> 01:45:56.000
Yeah, I don't think you can really get in enough
2054
01:45:56.000 --> 01:45:58.359
al dopa to get enough into your brain. That happened
2055
01:45:58.359 --> 01:46:01.159
to earlyer in neurology when it was discovered we couldn't
2056
01:46:01.159 --> 01:46:04.319
give our patients enough l dopa without them feeling bad
2057
01:46:04.359 --> 01:46:08.199
because it's also metabolized in the periphery. And so it
2058
01:46:08.279 --> 01:46:12.640
wasn't until we cinnemat came along, which has this debox
2059
01:46:12.680 --> 01:46:16.760
alse decopboxyist and hibre to block sort of the the
2060
01:46:16.800 --> 01:46:18.439
breakdown of don't mean that we were able to sort
2061
01:46:18.479 --> 01:46:19.960
of get enough don't mean into the brain.
2062
01:46:20.000 --> 01:46:20.640
So I'm not sure.
2063
01:46:20.720 --> 01:46:23.920
Yeah, so that's why I think it's not going to
2064
01:46:24.000 --> 01:46:26.439
probably get the levels up high enough in the brain.
2065
01:46:27.239 --> 01:46:33.600
So Parkins patients are given al dopa or bromacryptine or
2066
01:46:33.800 --> 01:46:36.199
drugs like that. Going back to Alzheimer's for a moment,
2067
01:46:36.319 --> 01:46:38.479
I mean, what do you tell somebody who has early
2068
01:46:38.479 --> 01:46:41.479
stage Alzheimer's. You just say, listen, try and get good sleep,
2069
01:46:41.760 --> 01:46:44.600
try and keep people around you, stay cognitively engaged, try
2070
01:46:44.600 --> 01:46:48.159
and keep those circuits going through behavioral induce neuroplasticity. But
2071
01:46:48.680 --> 01:46:53.000
we're just going to watch the steepness of the decline
2072
01:46:53.680 --> 01:46:54.560
that really is that.
2073
01:46:54.560 --> 01:46:57.319
Really all we've got, all we've got is such yeah,
2074
01:46:57.520 --> 01:47:00.119
is to help them with everything that comes up on
2075
01:47:00.119 --> 01:47:02.720
a day to day basis. A lot of the problems,
2076
01:47:03.319 --> 01:47:07.119
the memory problems tend to be something that families can
2077
01:47:07.279 --> 01:47:10.479
help compensate for. But you do get to a point
2078
01:47:10.479 --> 01:47:14.199
where you can't be with someone for twenty four to seven.
2079
01:47:14.239 --> 01:47:17.199
It's a real burnout for caregivers. A lot of the
2080
01:47:17.239 --> 01:47:21.119
behaviors that come up. Patients get kind of delusions and agitated,
2081
01:47:21.199 --> 01:47:25.399
and some of the medications that we use for other
2082
01:47:25.439 --> 01:47:29.439
conditions are helpful for treating that, but it's really just
2083
01:47:29.439 --> 01:47:34.760
a purely symptomatic therapy. And the more socialization that patients
2084
01:47:34.800 --> 01:47:36.720
get that they tend to do better. There was a
2085
01:47:36.760 --> 01:47:39.399
study back at pen way back that if you showed
2086
01:47:39.439 --> 01:47:43.840
patients some family movies or family albums, it was a
2087
01:47:43.880 --> 01:47:46.159
real co It was better than any drug you could
2088
01:47:46.159 --> 01:47:49.239
give them to sort of help their behavior. So there's
2089
01:47:49.239 --> 01:47:51.640
still those memories that are in there, and they were
2090
01:47:51.640 --> 01:47:55.199
making some type of contact that was helping them emotionally
2091
01:47:55.199 --> 01:47:57.560
that you couldn't turn off with with the drug. So
2092
01:47:57.600 --> 01:48:00.199
I think the more we do things like that that
2093
01:48:00.560 --> 01:48:03.600
more will be helpful for them, at least in a symptomatically.
2094
01:48:04.119 --> 01:48:06.960
Yeah, I've seen a number of videos and on social
2095
01:48:07.000 --> 01:48:10.000
media people with Alzheimer's who listen to a piece of
2096
01:48:10.079 --> 01:48:12.560
music or people with Parkinson's that hear a piece of
2097
01:48:12.640 --> 01:48:16.720
music and that seems to resurrect some at least emotion
2098
01:48:16.880 --> 01:48:19.960
context appropriate emotional state where he kind of brings the
2099
01:48:20.000 --> 01:48:21.680
person to the surface.
2100
01:48:22.760 --> 01:48:23.079
Again.
2101
01:48:24.920 --> 01:48:27.520
Yeah, it's a kind of a tragic situation for Alzheimer's
2102
01:48:27.600 --> 01:48:29.960
right now. It seems like if ever there was a
2103
01:48:29.960 --> 01:48:34.399
call to arms for the neurology community and biotech and
2104
01:48:34.960 --> 01:48:39.159
behavioral tech would be for for for Alzheimer's, for the
2105
01:48:39.159 --> 01:48:44.039
treatment of Alzheimer's. Absolutely, I will never ask a guest
2106
01:48:44.119 --> 01:48:48.760
to comment on the the good or bad behaviors of
2107
01:48:48.800 --> 01:48:53.359
other people except my own. But there's a Nobel Prize
2108
01:48:53.399 --> 01:48:58.199
winning neuroscientist and I visited him. He's in a big
2109
01:48:58.239 --> 01:49:02.279
East Coast school back in twenty ten, and during the
2110
01:49:02.279 --> 01:49:05.159
course of our one hour meeting, he consumed no fewer
2111
01:49:05.199 --> 01:49:09.359
than four pieces of nicorette gum, and I said, I
2112
01:49:09.359 --> 01:49:12.000
gotta ask, what's this about. By the way, he's extremely
2113
01:49:12.039 --> 01:49:16.920
sharp still and he said, oh, yeah, yeah, you know,
2114
01:49:16.960 --> 01:49:18.720
I used to be a smoker. But smoking is really
2115
01:49:18.720 --> 01:49:21.720
bad for you because you can get lung cancer. Dipping's
2116
01:49:21.760 --> 01:49:25.640
bad for you because you can get mouth cancer. But nicotine,
2117
01:49:25.840 --> 01:49:27.920
these are his words, by the way, is protective against
2118
01:49:27.960 --> 01:49:30.199
Parkinson's and Alzheimer's, and it keeps in my brain sharp.
2119
01:49:30.439 --> 01:49:34.840
So I chew nicorette all day long. And I thought, okay,
2120
01:49:34.840 --> 01:49:40.000
well he's not He is an MD, actually, and I thought, well,
2121
01:49:40.079 --> 01:49:42.520
that's interesting. And I did an episode of this podcast
2122
01:49:42.520 --> 01:49:45.000
on nicotine. It, by the way, he can raise blood pressure.
2123
01:49:45.079 --> 01:49:49.399
It's certainly smoking, vaping, dipping, or snuffing not good, bad,
2124
01:49:49.680 --> 01:49:52.560
don't do it. But there is some interest in the
2125
01:49:52.640 --> 01:49:56.760
use of nicotine as a cognitive enhancer. So I'd love
2126
01:49:56.800 --> 01:49:59.640
to know your thoughts on that, And I'd love to
2127
01:49:59.680 --> 01:50:03.920
know your thoughts on his statement about nicotine being a
2128
01:50:03.960 --> 01:50:08.319
potential way to stave off Parkinson's and Alzheimer's, with the
2129
01:50:08.359 --> 01:50:10.239
caveat that he just kind of threw that out there,
2130
01:50:10.239 --> 01:50:11.880
and this guy's sort of known for just kind of
2131
01:50:11.880 --> 01:50:13.800
throwing stuff out there every once in a while. I
2132
01:50:13.800 --> 01:50:15.399
have a feeling, you know who this person is. But
2133
01:50:16.600 --> 01:50:18.760
in any event, what gives.
2134
01:50:18.560 --> 01:50:21.720
Yeah, Well, I don't know anything about nicotine staving off
2135
01:50:21.760 --> 01:50:26.560
any neurodegener disorder, but nicotine was used, and it was
2136
01:50:26.680 --> 01:50:29.720
used in a number of early Alzheimer's studies just because
2137
01:50:29.720 --> 01:50:32.279
of its effect on the colinergic system.
2138
01:50:32.359 --> 01:50:34.479
So there is some truth to that.
2139
01:50:35.000 --> 01:50:39.600
The colinergic system is, you know, dysfunctional in Alzheimer's disease,
2140
01:50:39.640 --> 01:50:43.560
and boosting the colinergic system probably is beneficial. I mean,
2141
01:50:43.600 --> 01:50:46.840
the patients that we give the anticolonessary's inhibitors, there are
2142
01:50:46.840 --> 01:50:49.560
some families that say, yeah, he just he's remembering more
2143
01:50:49.600 --> 01:50:52.159
and he's just doing better. So there there, I've seen
2144
01:50:52.319 --> 01:50:56.720
positive things to it. It doesn't really slow the course
2145
01:50:56.800 --> 01:50:57.479
of the disease.
2146
01:50:57.560 --> 01:50:58.119
That's the problem.
2147
01:50:58.159 --> 01:51:01.800
That disease just carries on, even though symptomatically improving the symptoms.
2148
01:51:01.840 --> 01:51:04.039
And again, I think it's going to take both assele
2149
01:51:04.079 --> 01:51:07.520
calling and something else. I think we don't know should
2150
01:51:07.560 --> 01:51:09.600
we give dope mean with the with the nicotine or
2151
01:51:09.640 --> 01:51:11.600
the assyle calling or shuld wear a nuffern. I think
2152
01:51:11.600 --> 01:51:15.399
it's going to be a cocktail, which which again pharmaceutical companies,
2153
01:51:15.640 --> 01:51:19.560
you know, have not tried a cocktail of neuromodulators for Alzheimer's.
2154
01:51:19.720 --> 01:51:22.199
They've just tried Assel calling.
2155
01:51:22.920 --> 01:51:25.319
It sounds like you should be running the FDA. No
2156
01:51:25.439 --> 01:51:29.000
disrespect to the current people in charge, by the way,
2157
01:51:29.079 --> 01:51:33.760
but maybe actually I'm a big believer that there shouldn't
2158
01:51:33.760 --> 01:51:37.319
be individuals in charge of large organizations. There should be panels.
2159
01:51:37.800 --> 01:51:39.600
I mean, there's so much talk about diversity, but they
2160
01:51:39.680 --> 01:51:43.479
appoint individuals. You can't get it right anytime there's when
2161
01:51:43.479 --> 01:51:46.239
there's only one person by definition.
2162
01:51:45.800 --> 01:51:48.640
So committees, folks, committees.
2163
01:51:49.600 --> 01:51:54.359
Anyway, another editorial, are there any sex differences male female
2164
01:51:54.359 --> 01:51:55.159
differences in.
2165
01:51:57.000 --> 01:51:57.479
Sort of.
2166
01:51:59.039 --> 01:52:06.079
These dopamine les levels, working memory, injuries, concussion like things
2167
01:52:06.079 --> 01:52:11.960
that would direct people toward different routes of treatment given that,
2168
01:52:12.039 --> 01:52:14.359
you know, maybe there's more susceptibility in one case, maybe
2169
01:52:14.399 --> 01:52:19.359
less susceptibility. Maybe certain neurotransmitters are more effective in improving
2170
01:52:19.920 --> 01:52:21.840
symptoms in men versus women.
2171
01:52:21.880 --> 01:52:23.000
Do you see that in the clinic?
2172
01:52:24.279 --> 01:52:28.279
Yeah, that's a great question. There was Emily Jacobs, who's
2173
01:52:28.279 --> 01:52:31.880
a professor at UC Santa Barbara now in the psychology department,
2174
01:52:32.119 --> 01:52:34.760
when she was a gratitude in my lab, studied the
2175
01:52:34.880 --> 01:52:38.319
role of esergen on working memory and doper nurgic function.
2176
01:52:39.159 --> 01:52:41.119
And what she brought to my attention at the time
2177
01:52:41.159 --> 01:52:44.359
and was embarrassing that I didn't know, was that there's
2178
01:52:44.399 --> 01:52:47.439
the frontal lobes are full of estrogen receptors. There's probably
2179
01:52:47.520 --> 01:52:50.359
more esgen receptors in the frontal lobes than any other
2180
01:52:50.479 --> 01:52:53.079
part of the brain in men and women. Estrogen boosts'
2181
01:52:53.119 --> 01:52:57.319
is dope mean, So higher estrogen levels correlates with with
2182
01:52:57.479 --> 01:53:02.039
increased of dope met levels. And there was some anecdotal
2183
01:53:02.039 --> 01:53:06.159
evidence that in postmedipazzal women who were put on estrogen
2184
01:53:06.199 --> 01:53:09.319
that they're working memory improved, and there was a kind
2185
01:53:09.319 --> 01:53:12.640
of evolving link between estrogen and frontal low function. And
2186
01:53:12.680 --> 01:53:16.720
she did this amazing study where she studied healthy Berkeley
2187
01:53:16.800 --> 01:53:19.479
undergraduates at two points in time during the mental cycle
2188
01:53:19.479 --> 01:53:22.399
when estro was lowest and what was as highest, and
2189
01:53:22.439 --> 01:53:26.159
she also genotyped them for this enzyme they were talking
2190
01:53:26.199 --> 01:53:28.279
about to know if they were sort of lower or
2191
01:53:28.359 --> 01:53:32.159
higher on the dopmein level, and then put them in
2192
01:53:32.199 --> 01:53:35.359
the scan or a measured frontal low function and showed
2193
01:53:35.359 --> 01:53:38.640
that there was a clear the frontal low function was
2194
01:53:38.760 --> 01:53:41.439
modulated by where they were in their estroan cycle when
2195
01:53:41.439 --> 01:53:43.720
they were low estrogen, they were a low dope meaning,
2196
01:53:43.720 --> 01:53:45.800
and if they were low estrogen and low dope mean
2197
01:53:45.840 --> 01:53:49.239
to start, they were really had decreased frontal low function
2198
01:53:49.319 --> 01:53:53.520
and decreased working memory ability. So it fluctuated based on
2199
01:53:53.520 --> 01:53:58.000
this interaction between estrogen and dope mean, suggesting that you know,
2200
01:53:58.039 --> 01:54:01.720
not only the dope meaning it's important. Hormones are clearly
2201
01:54:02.039 --> 01:54:06.520
important and they work us synergistically. So you know, as
2202
01:54:06.560 --> 01:54:11.640
we're developing this cocktail, we certainly have to bring hormones
2203
01:54:11.640 --> 01:54:15.399
into the equation and learn more about it. There's just
2204
01:54:15.479 --> 01:54:19.399
so little information about hormones and cognition.
2205
01:54:20.239 --> 01:54:22.119
Yeah, one of the themes that's come out of some of
2206
01:54:22.119 --> 01:54:25.680
the episodes we've done with mds who specialize in endocrine
2207
01:54:25.720 --> 01:54:30.199
health is that for both men and for women, optimizing
2208
01:54:30.439 --> 01:54:33.680
estrogen levels is really important for cognition and vascular function.
2209
01:54:33.760 --> 01:54:37.840
I think people mistakenly hear, okay, testosterone men, you know,
2210
01:54:38.079 --> 01:54:41.119
estrogen women. Obviously, both hormones are present in men and women.
2211
01:54:41.159 --> 01:54:45.640
In fact, I think I know that testosterone levels and
2212
01:54:45.680 --> 01:54:48.159
women are actually higher than their estrogen levels.
2213
01:54:48.159 --> 01:54:50.000
When you look at when you sort of.
2214
01:54:51.399 --> 01:54:54.399
Use the same units of measure, it just so happens
2215
01:54:54.399 --> 01:54:57.239
that they still have lower testosterone on average than the
2216
01:54:57.279 --> 01:55:01.359
typical male, but that men who's estrogen levels are too
2217
01:55:01.479 --> 01:55:05.840
low suffer cognitive defects and vascular defects.
2218
01:55:05.840 --> 01:55:06.640
So this idea that.
2219
01:55:06.560 --> 01:55:11.000
More testosterone, lower estrogen in men is the is the ideal, right,
2220
01:55:11.119 --> 01:55:14.960
And uh, it just doesn't hold. It doesn't hold. I
2221
01:55:15.000 --> 01:55:16.600
mean unless you want to be dumb and have a
2222
01:55:16.640 --> 01:55:21.600
heart attack. It just doesn't. It just doesn't hold. Very interesting,
2223
01:55:21.760 --> 01:55:24.840
do we know what estrogen's doing there? Is it's specifically
2224
01:55:24.960 --> 01:55:28.680
raising dopamine. We don't have to get into the synaptic biology.
2225
01:55:28.840 --> 01:55:29.920
It's so interesting.
2226
01:55:30.359 --> 01:55:33.680
Yes, it's actually boosting dope mean activity.
2227
01:55:34.199 --> 01:55:36.319
So it's making more dopamine available. Yeah.
2228
01:55:36.479 --> 01:55:42.359
Yeah, it's really amazing. And and and to think about
2229
01:55:42.399 --> 01:55:46.079
it sort of fluctuating certainly during the mental cycle. We
2230
01:55:46.119 --> 01:55:48.600
can think about how much a fluctuate cyndidual woman over
2231
01:55:49.000 --> 01:55:51.680
thirty days. But then you can think across individuals. You
2232
01:55:51.720 --> 01:55:54.199
can think about how how much it can account for
2233
01:55:54.279 --> 01:55:58.199
individual differences. So not only sort of knowing your dope level,
2234
01:55:58.239 --> 01:56:02.000
but just knowing sort of este and Sarto is really
2235
01:56:02.079 --> 01:56:02.880
going to be important.
2236
01:56:03.399 --> 01:56:03.960
Interesting.
2237
01:56:04.479 --> 01:56:09.039
Is there any evidence that physical exercise can improve working memory?
2238
01:56:09.039 --> 01:56:14.119
And cognition separate from the known improvements in cardiovascular function
2239
01:56:14.199 --> 01:56:17.159
and blood flow to the brain that occur with exercise, Like,
2240
01:56:17.239 --> 01:56:21.199
is there anything about going for you know, a forty
2241
01:56:21.239 --> 01:56:24.319
five minute bout of exercise, you pick your favorite exercise,
2242
01:56:24.520 --> 01:56:29.399
and then doing cognitive work immediately afterward, when presumably the
2243
01:56:29.439 --> 01:56:32.039
catechola means dopamine or epineffort and neper effort are going
2244
01:56:32.039 --> 01:56:35.520
to be circulating at least in the blood at higher levels.
2245
01:56:36.239 --> 01:56:37.880
Has that stuff ever been explored?
2246
01:56:38.479 --> 01:56:40.640
In all of the groups around the country that are
2247
01:56:40.640 --> 01:56:44.079
trying to develop cognitive therapies, they've they often use aerobic
2248
01:56:44.159 --> 01:56:49.119
exercise as as another type of therapy. And so for example,
2249
01:56:49.159 --> 01:56:53.039
the group at Universe Illinois Champaign, our Cramer's group has
2250
01:56:53.399 --> 01:56:56.079
done aerobic exercise quite a bit and they can find
2251
01:56:56.079 --> 01:57:00.279
it just as effective as cognitive therapy and improving a
2252
01:57:00.319 --> 01:57:03.159
function just straight up aerobic exercise.
2253
01:57:03.359 --> 01:57:03.600
Wow.
2254
01:57:03.960 --> 01:57:07.119
And and so you know, the hard part in the
2255
01:57:07.159 --> 01:57:09.439
real world is how do you get you know, a
2256
01:57:09.520 --> 01:57:11.279
seven year eight year old you know, to do the
2257
01:57:11.359 --> 01:57:13.239
kind of aerobic cent But but now with.
2258
01:57:13.279 --> 01:57:14.640
You know, we come in bicycles.
2259
01:57:14.640 --> 01:57:17.640
And now there has been studies with seven year olds
2260
01:57:17.680 --> 01:57:20.960
with just putting them in mostly with overcoming bicycles. It's
2261
01:57:21.000 --> 01:57:22.800
sort of designing. We have to think about ways to
2262
01:57:22.840 --> 01:57:25.720
design exercise. I can get aerobics up, but it's it's
2263
01:57:25.800 --> 01:57:30.239
uh and you know, neurologists are starting I think, you know,
2264
01:57:30.319 --> 01:57:32.640
my field is starting to realize that there's there's we
2265
01:57:32.760 --> 01:57:35.880
got to tackle this at all, all every way we can.
2266
01:57:36.079 --> 01:57:37.920
And so now I'm hearing more, you know, you hear
2267
01:57:37.960 --> 01:57:40.920
more neurologists talk about that. You know, thirty years ago, no,
2268
01:57:41.000 --> 01:57:43.199
no neurologe would say you got exercise more, you know,
2269
01:57:43.359 --> 01:57:46.800
or just now it's talking about exercise and nutrition and
2270
01:57:46.880 --> 01:57:49.840
sleep and and uh, you know, it's all becoming sort
2271
01:57:49.840 --> 01:57:52.079
of part of our package of how we're going to
2272
01:57:52.239 --> 01:57:55.399
help our patients. But the Arabic decise is super is
2273
01:57:55.439 --> 01:57:58.199
super interesting, and I think it's going to be you
2274
01:57:58.239 --> 01:58:00.479
know that that kind of made me think that what
2275
01:58:00.520 --> 01:58:03.840
we didn't talk about was mindfulness. And so when we
2276
01:58:03.880 --> 01:58:05.760
add a lot of these studies also, if they add
2277
01:58:05.800 --> 01:58:11.560
mindfulness training to the hardcore goal management training, it's it's
2278
01:58:11.600 --> 01:58:16.720
better than just the executive training alone. Just learning skills
2279
01:58:16.760 --> 01:58:21.159
to stop, relax, refocus kind of gives this sort of
2280
01:58:21.239 --> 01:58:24.039
boost to executive function as well.
2281
01:58:24.159 --> 01:58:26.840
Yeah, I think of mindfulness like sort of well, there's
2282
01:58:26.880 --> 01:58:28.840
no such thing as traditional meditation. I have to be
2283
01:58:28.880 --> 01:58:33.159
careful here, but they sort of stereotypical meditation of closing
2284
01:58:33.159 --> 01:58:37.439
one's eyes, closing one's eyes, excuse me, sitting down, lying down,
2285
01:58:37.640 --> 01:58:41.079
and just focusing on one's breath and then redirecting one's
2286
01:58:41.079 --> 01:58:43.720
focus to maybe third eye center, you know, area between
2287
01:58:43.720 --> 01:58:47.119
the forehead, just redirecting focus, redirector. I think of meditation
2288
01:58:47.239 --> 01:58:51.000
of that sort as a focus exercise. Rights, it's not
2289
01:58:51.039 --> 01:58:53.399
so much a perceptual exercise because thoughts.
2290
01:58:53.199 --> 01:58:56.319
Are kind of you know, doing what they're doing. It's
2291
01:58:56.359 --> 01:58:57.560
like a focus exercise.
2292
01:58:57.720 --> 01:59:00.720
And that's half of the problem with not achieving our goals,
2293
01:59:00.800 --> 01:59:04.520
right as we lose our focus and so building into
2294
01:59:04.520 --> 01:59:08.479
sort of strategies to main focus, you know, to stop
2295
01:59:08.560 --> 01:59:13.399
and lacks some refocus is an important strategy for boosting
2296
01:59:13.439 --> 01:59:17.159
executive function. So that and it doesn't seem to matter
2297
01:59:17.199 --> 01:59:21.039
what you know. I know, there's all different flavors of mindfulness,
2298
01:59:21.039 --> 01:59:22.000
So we just happened to.
2299
01:59:22.000 --> 01:59:23.479
Use one when we were studying it.
2300
01:59:23.479 --> 01:59:25.840
It doesn't yet, I don't think we know enough about
2301
01:59:25.920 --> 01:59:28.920
how we should tell her the mindfulness, but most forms
2302
01:59:28.920 --> 01:59:31.840
of mindfulness will work of the type you're talking about.
2303
01:59:31.920 --> 01:59:34.079
That's similar what I described as similar to what you
2304
01:59:34.520 --> 01:59:35.479
explored exactly.
2305
01:59:35.640 --> 01:59:36.359
Yeah, I mean.
2306
01:59:36.279 --> 01:59:37.199
It's amazing to me.
2307
01:59:37.399 --> 01:59:40.840
You know, twenty years ago, if somebody wanted to talk
2308
01:59:40.840 --> 01:59:44.760
about neuroscience and mindfulness on a major university campus, let's
2309
01:59:44.800 --> 01:59:47.079
say Stanford or Berkeley, is probably a little bit more
2310
01:59:47.119 --> 01:59:49.920
toleranted these ideas at that time, just given the kind
2311
01:59:49.960 --> 01:59:53.520
of culture, they wouldn't have been laughed out of the room.
2312
01:59:53.560 --> 01:59:56.279
But there was a lot of skepticism. And I feel
2313
01:59:56.319 --> 02:00:01.399
like now mindfulness, meditation, breath work idea that, oh my goodness,
2314
02:00:01.439 --> 02:00:03.079
breathing can impact your emotional state.
2315
02:00:03.359 --> 02:00:05.039
Yeah, I mean that should have been obvious.
2316
02:00:05.399 --> 02:00:07.079
But now that people are on board that and now
2317
02:00:07.079 --> 02:00:09.199
of course there's a lot of interest in psychedelics. That's
2318
02:00:09.279 --> 02:00:12.760
kind of a new emerging therapy carrying more risk, potential risk,
2319
02:00:13.079 --> 02:00:16.279
but it looks like it's very likely that some of
2320
02:00:16.319 --> 02:00:18.560
those are going to make it through the FDA filters
2321
02:00:18.600 --> 02:00:23.079
at some point. But the conversation we're having now, neurologist
2322
02:00:23.399 --> 02:00:28.640
neurobiologists talking about mindfulness nutrition, we're talking freely about nicotine.
2323
02:00:28.880 --> 02:00:31.279
You know, we're not suggesting people do that bromacryptine as
2324
02:00:31.319 --> 02:00:35.039
it to optimize cognitive function. I mean this conversation would
2325
02:00:35.079 --> 02:00:36.960
have never happened.
2326
02:00:40.000 --> 02:00:42.960
Seven years ago. No, it's just the field has changed.
2327
02:00:43.039 --> 02:00:45.720
Yeah, I hear neurologists talk about it all the time.
2328
02:00:46.039 --> 02:00:48.960
So do you try mindfulness? And if you do, does
2329
02:00:49.000 --> 02:00:51.039
it make your day? Do you feel like you performed
2330
02:00:51.079 --> 02:00:51.640
better that day?
2331
02:00:51.720 --> 02:00:51.920
Yeah?
2332
02:00:51.920 --> 02:00:54.399
Thanks for asking. There are two forms of yes. The
2333
02:00:54.399 --> 02:00:59.079
short answer is yes. There's a very specific practice that
2334
02:00:59.119 --> 02:01:02.600
I've used since twenty seventeen that's really benefited me so much,
2335
02:01:02.640 --> 02:01:05.000
which is what I call it non sleep deep breast.
2336
02:01:05.039 --> 02:01:07.079
But it's based on a practice called yoga nidro where
2337
02:01:07.119 --> 02:01:10.199
you just lie down and it's These are free audio
2338
02:01:10.199 --> 02:01:13.319
scripts online. We can provide links to these, and you
2339
02:01:13.319 --> 02:01:15.359
go through a body scan and you do some long
2340
02:01:15.399 --> 02:01:19.399
axhale breathing, which emphasizes the parasympathetic aka relaxing aspect of
2341
02:01:19.439 --> 02:01:20.560
the autonomic nervous system.
2342
02:01:20.600 --> 02:01:21.159
I know you know this.
2343
02:01:21.239 --> 02:01:24.119
I'm saying that for the audience, and it does involve
2344
02:01:24.119 --> 02:01:26.239
some intentions and things like that, but it can also
2345
02:01:26.399 --> 02:01:30.399
just be self directed relaxation and I emerge from that
2346
02:01:30.439 --> 02:01:33.319
with much more mental and physical vigor than I did prior,
2347
02:01:33.359 --> 02:01:35.600
and this only takes maybe ten minutes. There's also thirty
2348
02:01:35.640 --> 02:01:39.520
minute scripts. I do those and then I do mindfulness meditation.
2349
02:01:40.000 --> 02:01:43.000
The thing about mindfulness meditation that the biggest impact for
2350
02:01:43.079 --> 02:01:49.600
me has been the problems of my life get re.
2351
02:01:51.600 --> 02:01:52.800
I get a different perspective.
2352
02:01:53.199 --> 02:01:55.720
I start thinking about things in different domains of time,
2353
02:01:56.399 --> 02:01:58.720
like this thing that is like a problem that I've
2354
02:01:58.720 --> 02:02:01.479
been dealing with, for instance, And I start thinking, you know,
2355
02:02:01.560 --> 02:02:03.520
like in the course of my lifetime, this is you know,
2356
02:02:03.720 --> 02:02:07.239
a relatively small, not small thing, but in relatively small
2357
02:02:07.279 --> 02:02:09.319
time being and I sort of think about, you know,
2358
02:02:09.600 --> 02:02:12.720
best course of action given its real role in my
2359
02:02:12.800 --> 02:02:14.680
life and what I want, et cetera. So I feel
2360
02:02:14.680 --> 02:02:18.000
like it sort of orients me in time. So that's
2361
02:02:18.000 --> 02:02:21.800
been a major effect for focus. The best tool I
2362
02:02:21.840 --> 02:02:24.760
know is to, you know, put the phone in another room,
2363
02:02:25.560 --> 02:02:28.399
but that's kind of a don't. And I know our
2364
02:02:28.439 --> 02:02:31.800
friend Eddie Chang, neurosurgeon, Chair of neurosurgery at UCSF, he's
2365
02:02:31.800 --> 02:02:33.439
big on unmindfulness meditation.
2366
02:02:33.960 --> 02:02:34.840
So do you meditate?
2367
02:02:35.119 --> 02:02:35.159
No?
2368
02:02:35.319 --> 02:02:37.199
I think that's one of the things we were talking about.
2369
02:02:37.199 --> 02:02:39.680
What should we do besides reading fiction? I think that's
2370
02:02:40.000 --> 02:02:43.079
that should be on my list because because because I know,
2371
02:02:43.199 --> 02:02:46.239
I guess it's just amazing that I the patients tell
2372
02:02:46.279 --> 02:02:48.680
me about it and what we've seen from our studies,
2373
02:02:49.960 --> 02:02:51.600
you know, a lot of this. Like again I was
2374
02:02:51.640 --> 02:02:55.039
saying before, is if we had some measure of you know,
2375
02:02:55.319 --> 02:02:57.439
brain health that we could see the impact of, it
2376
02:02:57.479 --> 02:03:00.479
would sort of push us towards arts, you know, probably
2377
02:03:00.479 --> 02:03:02.880
doing it more. I think another thing that we didn't
2378
02:03:02.880 --> 02:03:04.399
sort of talk about we talked a little about with
2379
02:03:04.439 --> 02:03:07.319
Don't mean is are there other kind of brain states
2380
02:03:07.359 --> 02:03:10.520
that sort of you know, predict you know, you know,
2381
02:03:10.560 --> 02:03:13.399
how you're going to respond to these therapies and how
2382
02:03:13.640 --> 02:03:17.000
if you're going to benefit from them. And uh, you know,
2383
02:03:17.039 --> 02:03:18.520
we've we've done a lot of work with sort of
2384
02:03:18.560 --> 02:03:20.960
measuring sort of the large scale organization of the brain
2385
02:03:21.000 --> 02:03:23.800
and brain networks, and that's sort of very popular idea
2386
02:03:23.840 --> 02:03:26.880
in neuroscience today, sort of moving away from sort of
2387
02:03:26.880 --> 02:03:28.439
what is this We've talked a lot about what the
2388
02:03:28.439 --> 02:03:31.079
frontal loves do, but the frontal loves are part of
2389
02:03:31.720 --> 02:03:35.560
these networks in the brain and and really sort of
2390
02:03:35.600 --> 02:03:38.960
your the state of your networks is really important factor
2391
02:03:38.960 --> 02:03:41.800
as well. In addition to sort of your your dot
2392
02:03:41.880 --> 02:03:45.439
your sort of neuromodule, you know, sort of neurochemical profile.
2393
02:03:45.920 --> 02:03:48.800
Yeah, tell me more about this. I mean, you actually
2394
02:03:49.039 --> 02:03:52.039
uh preempted my next question, which was going to be
2395
02:03:52.119 --> 02:03:54.600
and this is my favorite question to ask. Carl Diaser
2396
02:03:54.800 --> 02:03:57.199
taught me to ask this way back when, Like, what
2397
02:03:57.239 --> 02:03:59.159
are you most excited about now?
2398
02:03:59.399 --> 02:04:01.279
Because I know the work you've published.
2399
02:04:00.880 --> 02:04:03.560
And and you've done a magnificent job of sharing the
2400
02:04:03.600 --> 02:04:06.920
details of that and work of others in a really
2401
02:04:06.920 --> 02:04:09.000
informative and in some cases actionable way.
2402
02:04:09.039 --> 02:04:11.439
But what do you what are you really excited about?
2403
02:04:11.560 --> 02:04:16.319
Like if if there were no financial barriers to your grants,
2404
02:04:16.319 --> 02:04:18.880
et cetera, you had a thousand people working, what what's
2405
02:04:19.000 --> 02:04:22.560
the what's the thing that's hitting your dopamine circuits these days?
2406
02:04:23.239 --> 02:04:26.560
Well, in the grand scale, I'm excited that things that
2407
02:04:26.600 --> 02:04:28.880
we've learned over the last thirty years, not just in
2408
02:04:28.960 --> 02:04:31.239
my lab or your lab or anyone's lab, is actually
2409
02:04:31.279 --> 02:04:35.279
now being translated to actually helping people. I Mean, when
2410
02:04:35.319 --> 02:04:37.880
people ask me what I do, I say I'm a neurologist,
2411
02:04:37.960 --> 02:04:40.279
because that's at my core what I feel I am,
2412
02:04:40.319 --> 02:04:44.039
and I feel I got into this business to help people,
2413
02:04:44.039 --> 02:04:47.039
and so it's it's when you when you work for
2414
02:04:47.159 --> 02:04:50.760
years and years and years and it doesn't translate it
2415
02:04:50.520 --> 02:04:53.920
it can be frustrating. But now I'm excited that it
2416
02:04:54.119 --> 02:04:56.159
seems that the things we've learned, that all of aus
2417
02:04:56.239 --> 02:04:58.880
have learned and neuro science is starting to now translate
2418
02:04:58.880 --> 02:05:02.760
into something isn't something in neuroscience. What's sort of what's
2419
02:05:02.800 --> 02:05:04.960
happened the last ten years we've been thinking of the
2420
02:05:05.000 --> 02:05:09.159
brain and in a kind of grander scale, is sort
2421
02:05:09.199 --> 02:05:12.760
of its overall organization and not so focused on just
2422
02:05:12.920 --> 02:05:15.439
this area or that area. When I when I talk
2423
02:05:15.479 --> 02:05:19.119
about the front of loves as being the most important part,
2424
02:05:19.319 --> 02:05:23.720
you know, the conductor. Yes, I am talking about one
2425
02:05:23.720 --> 02:05:26.000
brain region, but it's a brain region, like I said,
2426
02:05:26.000 --> 02:05:28.640
that's connected to everywhere. And it's because it's connected to
2427
02:05:28.680 --> 02:05:32.640
everywhere is what's really the essence of why it's it's
2428
02:05:32.680 --> 02:05:35.960
so important. So some of the research I'm excited most
2429
02:05:35.960 --> 02:05:38.399
about it sort of taking away the names of areas
2430
02:05:38.399 --> 02:05:40.800
and just thinking about the brain as a as a
2431
02:05:41.640 --> 02:05:45.039
big network like a like an airline network or or
2432
02:05:45.199 --> 02:05:50.039
electrical network, and how different areas communicate with each other
2433
02:05:50.199 --> 02:05:52.359
and when you think of it that way. So, for example,
2434
02:05:52.359 --> 02:05:55.079
an airline network, you've got all these hubs all over
2435
02:05:55.119 --> 02:05:58.279
the world, all over the country. In the United States,
2436
02:05:58.319 --> 02:06:02.560
for example, you've got Chicago is a hub, and there's
2437
02:06:02.640 --> 02:06:06.079
other hub Milwaukee or Cincinnati, but they have very different
2438
02:06:06.319 --> 02:06:09.720
functions in the network as a whole. Right, if you're
2439
02:06:09.720 --> 02:06:13.800
trying to get from New York to San Francisco, which
2440
02:06:13.880 --> 02:06:16.439
happened to me many times, even though you're not going
2441
02:06:16.439 --> 02:06:20.560
through Chicago, if Chicago's shut down, you're probably going to
2442
02:06:20.640 --> 02:06:23.359
get delayed because it just has this huge impact on
2443
02:06:23.439 --> 02:06:27.239
the whole system. And you know, if Milwaukee goes down, you.
2444
02:06:27.159 --> 02:06:29.279
Don't even know it. You just fly right over there.
2445
02:06:29.399 --> 02:06:30.880
I'm sorry, if anyone's listening.
2446
02:06:30.680 --> 02:06:32.439
From there, probably a few.
2447
02:06:32.960 --> 02:06:33.880
You got to go through.
2448
02:06:33.960 --> 02:06:36.760
But so thinking about the brain, the brain is the
2449
02:06:36.760 --> 02:06:39.600
same way. The brain has these hubs as well. And
2450
02:06:40.199 --> 02:06:43.439
you know, the prefrontal cortex is a hub like Chicago.
2451
02:06:43.600 --> 02:06:48.479
It's just an important hub that keeps the whole system going.
2452
02:06:48.680 --> 02:06:51.119
And that's why it has much more of an impact
2453
02:06:51.199 --> 02:06:54.640
when you when you when you damage it or you
2454
02:06:54.720 --> 02:06:57.199
stress it as opposed to some other part of the brain.
2455
02:06:57.239 --> 02:06:58.840
And so what's exciting to me, is not only is
2456
02:06:58.880 --> 02:07:01.960
that make us thinking about disease differently, because now we're
2457
02:07:02.000 --> 02:07:06.079
starting to think about how is diseases affecting these hubs
2458
02:07:06.119 --> 02:07:08.960
that the pathology seems to be. Like when you look
2459
02:07:08.960 --> 02:07:11.439
at Alzheimer's disease and you look at schizophrenia, and you
2460
02:07:11.439 --> 02:07:14.079
look at a lot of diseases, it's not just that
2461
02:07:14.119 --> 02:07:17.079
there's some microscopic change and some neuron It seems to
2462
02:07:17.079 --> 02:07:20.680
be affecting hubs in the brain that are affecting the
2463
02:07:20.680 --> 02:07:23.159
whole network. And so we have a different target to
2464
02:07:23.199 --> 02:07:26.239
go after for treatments. What can we do to sort
2465
02:07:26.239 --> 02:07:29.960
of boost, you know, a hub that's been damaged as
2466
02:07:29.960 --> 02:07:33.359
opposed to thinking about it in a less specific way.
2467
02:07:33.600 --> 02:07:37.439
And then also as we've as we've really start to
2468
02:07:37.520 --> 02:07:40.079
learn about how the brain is organized in these networks,
2469
02:07:40.159 --> 02:07:44.560
we've also learned that in measuring your network structure is
2470
02:07:44.640 --> 02:07:48.399
very predictive of of your well being and how you
2471
02:07:48.479 --> 02:07:53.760
respond to interventions. So there's a metrical modularity which measures
2472
02:07:54.760 --> 02:07:58.479
how organized your brain networks are. And the brain is
2473
02:07:58.520 --> 02:08:02.960
made up of different modules, different networks, and these networks
2474
02:08:02.960 --> 02:08:05.560
can either be very communicating with each other or not
2475
02:08:05.600 --> 02:08:09.880
so communicating with each other, and the more segregated they are,
2476
02:08:10.159 --> 02:08:14.279
we call that more modularity. They're kind of separate entities.
2477
02:08:14.399 --> 02:08:17.800
They're modular, and it turns out we can measure that
2478
02:08:17.840 --> 02:08:20.199
with fm RII we can put someone in a scanner.
2479
02:08:20.279 --> 02:08:24.079
We can do this resting fMRI scanning, and then we
2480
02:08:24.119 --> 02:08:27.000
can measure how modular your brain is versus my brain,
2481
02:08:27.039 --> 02:08:30.199
and all of us are very different levels of modularity.
2482
02:08:30.520 --> 02:08:33.880
Is it more advantageous to have more modularity as opposed
2483
02:08:33.880 --> 02:08:34.399
to less?
2484
02:08:34.600 --> 02:08:36.359
Yeah, it turns out that it seems to be more
2485
02:08:36.359 --> 02:08:39.279
advantation to have more, so we can predict.
2486
02:08:38.880 --> 02:08:41.279
More separateness of brain function between areas.
2487
02:08:41.359 --> 02:08:44.119
Yeah, that the networks are sort of more independent. That
2488
02:08:44.119 --> 02:08:46.239
doesn't mean they don't talk to each other, but at
2489
02:08:47.000 --> 02:08:51.800
sort of baseline they're more resting. Yeah, they're more they're
2490
02:08:51.840 --> 02:08:55.560
more independent as opposed to less independent with each other.
2491
02:08:55.840 --> 02:09:00.399
Not unlike neuromuscular junctions, the development are what we call pollinevated.
2492
02:09:00.880 --> 02:09:02.720
That's why babies can move their limbs, but not with
2493
02:09:02.760 --> 02:09:05.119
a lot of coordination. Look at a one year old
2494
02:09:05.119 --> 02:09:07.880
trying to eat spaghetti, for instance. It's hilarious, right, Look
2495
02:09:07.880 --> 02:09:10.279
at that same kid seven months later. There's a lot
2496
02:09:10.319 --> 02:09:13.920
more precision, a movement largely due to removal more modularity
2497
02:09:13.920 --> 02:09:15.600
of connections.
2498
02:09:15.079 --> 02:09:16.439
Right right, interesting.
2499
02:09:16.520 --> 02:09:19.720
So we did a study where we took twelve traumatic
2500
02:09:19.760 --> 02:09:23.359
brainery patients and measured the modularity, so you get a number,
2501
02:09:23.520 --> 02:09:25.279
you know, you just get a modulary index for each
2502
02:09:25.279 --> 02:09:28.560
of the twelves people, and then they underwent this goal
2503
02:09:28.640 --> 02:09:31.880
management training and we were able to predict who was
2504
02:09:31.960 --> 02:09:35.199
going to improve on the training, that those who had
2505
02:09:35.239 --> 02:09:39.560
more started off more modular benefited more from the training.
2506
02:09:39.960 --> 02:09:41.720
And it's turned out that this has been a very
2507
02:09:41.840 --> 02:09:47.600
robust finding across studies now, across different training, different young,
2508
02:09:47.760 --> 02:09:52.520
old patient populations. It's also predicted things like whether someone
2509
02:09:52.600 --> 02:09:55.840
in a coma is more likely to do well, or
2510
02:09:55.840 --> 02:09:58.439
if someone who's older is going to have a certain
2511
02:09:58.439 --> 02:10:00.800
amount of cognitive cline, or no one's going to respond
2512
02:10:00.840 --> 02:10:04.880
to behavioral therapy if they're obsessive compulsive. So there's something
2513
02:10:04.920 --> 02:10:07.760
about this brain state that not only we can measure,
2514
02:10:07.800 --> 02:10:11.560
but actually it is giving us insight into the interventions
2515
02:10:11.600 --> 02:10:13.640
that we're doing, which again is going to be much
2516
02:10:13.680 --> 02:10:18.159
more helpful in determining what helps and what doesn't help
2517
02:10:18.199 --> 02:10:20.960
if we know we know sort of what the state
2518
02:10:21.039 --> 02:10:23.239
is before we start the intervention.
2519
02:10:23.319 --> 02:10:28.439
So interesting and makes me think many things, but I'll
2520
02:10:28.479 --> 02:10:30.439
just focus on two of them. One is, I love
2521
02:10:30.439 --> 02:10:33.520
this idea that you and others are starting to look
2522
02:10:33.560 --> 02:10:38.039
at brain network activity as opposed to overemphasizing the role
2523
02:10:38.079 --> 02:10:41.439
of say, prefrontal cortex or hippocampus, understanding more that those
2524
02:10:41.479 --> 02:10:44.079
are hubs in a larger theme of.
2525
02:10:45.640 --> 02:10:46.159
Activation.
2526
02:10:46.279 --> 02:10:49.479
Because if I had one wish for science communication, it's
2527
02:10:49.479 --> 02:10:52.039
that people would yes learn some terms like dopamine and
2528
02:10:52.079 --> 02:10:54.960
frontal lobes. It is important to know the nomenclature, but
2529
02:10:55.039 --> 02:10:57.920
to understand that if you really want to be able
2530
02:10:57.920 --> 02:11:00.000
to work with the information in a way that's benefit,
2531
02:11:00.239 --> 02:11:00.760
you need to think.
2532
02:11:00.680 --> 02:11:02.319
About verbs, not nouns.
2533
02:11:02.880 --> 02:11:06.039
It's about the action states of these areas, and those
2534
02:11:06.079 --> 02:11:11.000
action states are always involving multiple areas, just like you
2535
02:11:11.039 --> 02:11:13.800
can't talk about running as just like quadrucep and hamstring
2536
02:11:14.159 --> 02:11:16.720
inflection and extension and you know, and contractions.
2537
02:11:17.560 --> 02:11:18.079
You can.
2538
02:11:18.319 --> 02:11:20.279
You can break it down that way, and it's useful
2539
02:11:20.279 --> 02:11:24.039
to know that, but ultimately you're talking about gate and
2540
02:11:24.119 --> 02:11:28.199
stride and things that have a real verb action to them,
2541
02:11:28.199 --> 02:11:29.720
and we haven't had so much of that for the
2542
02:11:29.760 --> 02:11:32.680
nervous system at a circuit level. We've been able to
2543
02:11:32.680 --> 02:11:35.399
do that for individual neurons. That's the first piece, and
2544
02:11:35.479 --> 02:11:38.920
then the second piece is that, you know, it occurs
2545
02:11:38.960 --> 02:11:44.239
to me that there's so much rich understanding of the
2546
02:11:44.279 --> 02:11:47.199
different states of sleep. You know, Matt Walker was just
2547
02:11:47.199 --> 02:11:49.960
here recording this series on sleep that will release later
2548
02:11:50.000 --> 02:11:52.399
this year, and your stage is one, two, three, four,
2549
02:11:52.520 --> 02:11:55.439
deep sleep, slow wave sleep, wrap, an eye movement sleep.
2550
02:11:55.479 --> 02:11:58.520
But we don't even really have a naming.
2551
02:11:59.119 --> 02:12:04.039
System for states, like we say focus, we say task switching,
2552
02:12:04.159 --> 02:12:08.640
but those are just names we made up, just as
2553
02:12:08.720 --> 02:12:10.840
stage one, two three and rem sleeper names that we
2554
02:12:10.840 --> 02:12:12.600
made up. But there seems to be a much richer
2555
02:12:12.680 --> 02:12:15.079
understanding of like what rapid I movement sleep is good for,
2556
02:12:15.239 --> 02:12:16.640
and what deficits and rapid eye.
2557
02:12:16.560 --> 02:12:17.640
Movement sleep lead to.
2558
02:12:18.039 --> 02:12:22.399
Then there is, for instance, how given our network, I'm
2559
02:12:22.399 --> 02:12:24.920
gonna make this up, like calling a certain network activation
2560
02:12:25.079 --> 02:12:26.199
state like state A.
2561
02:12:27.840 --> 02:12:29.359
Like what I feel like.
2562
02:12:29.399 --> 02:12:32.119
Neuroscience is tasked the field of neuroscience now is tasked
2563
02:12:32.119 --> 02:12:35.000
with with giving us an understanding of the verb states
2564
02:12:35.000 --> 02:12:36.960
and like what like these waking states of mind are
2565
02:12:37.079 --> 02:12:40.039
very mysterious and for the general public This is important
2566
02:12:40.079 --> 02:12:44.520
because people wonder like is my focus poor or is
2567
02:12:44.560 --> 02:12:46.840
it good? Is my task switching ability good? I mean,
2568
02:12:46.840 --> 02:12:48.720
we only tend to look at you know, are they
2569
02:12:48.720 --> 02:12:52.359
functional enough to do their job and manage their family,
2570
02:12:52.399 --> 02:12:55.000
manage their lives. We don't really have metrics, but for
2571
02:12:55.079 --> 02:12:57.560
sleep we have metrics, and commercial products can measure that,
2572
02:12:57.600 --> 02:13:00.199
you know, sleep track of rings, risk bands, metrics cover that.
2573
02:13:00.239 --> 02:13:02.039
I mean this sort of thing.
2574
02:13:02.159 --> 02:13:05.600
Well, you know, yeah, I think modularity can actually be
2575
02:13:05.720 --> 02:13:10.560
that metric, some metric of your large scale organization of
2576
02:13:10.600 --> 02:13:13.319
your of your brain can be that metric. We've there's
2577
02:13:13.359 --> 02:13:15.760
a number of labs that have done this, have measured
2578
02:13:15.760 --> 02:13:18.720
modularity in real time. So what I was talking about
2579
02:13:18.760 --> 02:13:20.800
was just getting a snapshot of this is what your
2580
02:13:20.800 --> 02:13:24.079
baseline modularity is. But we can also look at modularity
2581
02:13:24.159 --> 02:13:26.760
have changes on a second to second to minute to
2582
02:13:26.840 --> 02:13:30.800
minute basis. And one of my foreign posts except at
2583
02:13:30.840 --> 02:13:32.600
a side of the Hunties, she just did a very
2584
02:13:32.640 --> 02:13:36.880
simple experiment where there were noise, there were sounds, and
2585
02:13:37.000 --> 02:13:40.399
the functional rice scare is very loud, so you can't
2586
02:13:40.439 --> 02:13:42.720
hear very well, but every once in a while there'd
2587
02:13:42.720 --> 02:13:45.560
be a sound that was just above the level of
2588
02:13:45.640 --> 02:13:48.199
the noise of the of the scanner, and all you
2589
02:13:48.319 --> 02:13:50.840
had to do was sort of, you know, press a button.
2590
02:13:50.840 --> 02:13:53.119
If you heard that sound and you didn't pick it
2591
02:13:53.239 --> 02:13:55.319
up all the time, you know, you maybe eighty percent
2592
02:13:55.319 --> 02:13:57.880
of the time you heard and sometimes twenty percent of
2593
02:13:57.960 --> 02:14:01.079
times you didn't hear it. Well, she measured their modularity
2594
02:14:01.680 --> 02:14:04.560
on a moment to moment basis, and she could predict
2595
02:14:04.600 --> 02:14:06.720
if they were going to get that, if they were
2596
02:14:06.760 --> 02:14:08.840
going to be correct or not, and rec and break
2597
02:14:08.920 --> 02:14:11.279
the sound before they got the sound. If they were
2598
02:14:11.279 --> 02:14:14.920
a highly modular boom, they got it. If their brain
2599
02:14:15.000 --> 02:14:17.720
had gone into this kind of you know, diffuse less
2600
02:14:17.800 --> 02:14:19.159
minor state, they missed it.
2601
02:14:19.520 --> 02:14:22.159
And so I could definitely see as you're talking.
2602
02:14:21.960 --> 02:14:25.039
About, where if we could develop a modularity metric in
2603
02:14:25.159 --> 02:14:29.239
real time on a device, this would be game changer.
2604
02:14:29.359 --> 02:14:31.560
And so and that's sort of what I'm you know,
2605
02:14:31.640 --> 02:14:33.720
what I've been interested in do. What's excites me is
2606
02:14:33.760 --> 02:14:35.880
that we're not going to do with a skin. Obviously,
2607
02:14:36.439 --> 02:14:38.359
you can't walk around with a skinner in your head,
2608
02:14:38.439 --> 02:14:40.680
right and even I don't think you could even do
2609
02:14:40.760 --> 02:14:44.239
with the eg I think can we develop a proxy
2610
02:14:44.520 --> 02:14:48.199
for modularity with some more simple way of doing it.
2611
02:14:48.359 --> 02:14:51.479
Can we extract this maybe out of heart rate variability
2612
02:14:51.720 --> 02:14:57.760
or for oxygen. I've been I've been working with some colleagues,
2613
02:14:57.880 --> 02:15:03.079
the former student Brian Miller and a postdoc of Adam
2614
02:15:03.119 --> 02:15:06.119
Gazally's West Clap who have a company called Neuse Scouting
2615
02:15:06.800 --> 02:15:10.800
where they are able to They have we've been sort
2616
02:15:10.840 --> 02:15:15.520
of doing scanning and also collecting physiological data to try
2617
02:15:15.560 --> 02:15:17.760
and determine if there's some problem. We can measure the
2618
02:15:17.840 --> 02:15:20.199
modular in the scanner, but can we pick that up
2619
02:15:20.439 --> 02:15:23.119
in the in the physiology data because they can collect
2620
02:15:23.600 --> 02:15:27.159
you know, oxygen and heart rate variability and other metrics
2621
02:15:27.199 --> 02:15:29.640
that may be kind of a readout of that, and
2622
02:15:29.720 --> 02:15:31.960
then then we'd have a brain state, which is what
2623
02:15:32.079 --> 02:15:34.359
you were looking. You know, you're looking for some brain state,
2624
02:15:34.439 --> 02:15:36.560
but it's not. I think people are thinking, we're going
2625
02:15:36.720 --> 02:15:39.239
we need a helmet or something like that. We need
2626
02:15:39.399 --> 02:15:42.279
just something simple, right that reads out brain state, just
2627
02:15:42.359 --> 02:15:47.279
the way we read out other physiological information from our
2628
02:15:47.399 --> 02:15:49.399
watch or or something like that.
2629
02:15:49.760 --> 02:15:52.199
Well, the sleep trackers of various kinds have certainly been
2630
02:15:52.199 --> 02:15:54.960
able to pull out information about rabbit eye movement and
2631
02:15:55.079 --> 02:15:57.760
other stages of sleep. I mean key metrics, not every metric,
2632
02:15:57.960 --> 02:16:00.640
and not what you would get with a person wearing eeg.
2633
02:16:02.039 --> 02:16:04.520
You know probe or something, you know, set of probes,
2634
02:16:04.920 --> 02:16:08.399
but certainly information that can be used. One thing that
2635
02:16:08.520 --> 02:16:13.640
has me a little bit perplexed, and I'm almost reluctant
2636
02:16:13.640 --> 02:16:15.760
to bring it up, but I'm gonna do it, is
2637
02:16:15.840 --> 02:16:19.640
that I did a couple episodes about psilocybin and the
2638
02:16:19.840 --> 02:16:24.680
use of psilocybin for the treatment of depression. This is
2639
02:16:24.960 --> 02:16:27.560
Robin Carterart Harris from UCSF and I also just solo
2640
02:16:27.640 --> 02:16:30.560
episode emphasizing of course this isn't recreational use we're talking about.
2641
02:16:30.560 --> 02:16:33.120
We're talking about for treatment of depression. But there's a
2642
02:16:33.159 --> 02:16:39.040
lot of neuroimaging about of patients before and after macrodose psilocybin,
2643
02:16:39.079 --> 02:16:41.920
and this isn't microdosing. And one of the major takeaways
2644
02:16:42.000 --> 02:16:46.360
is increased resting state connectivity, which by virtue of what
2645
02:16:46.479 --> 02:16:51.440
you just described, might not be ideal for cognitive function,
2646
02:16:51.559 --> 02:16:56.399
it might be good for social emotional function. And I
2647
02:16:56.559 --> 02:16:59.920
certainly don't want to disparage the beautiful work that's been
2648
02:17:00.079 --> 02:17:04.639
done there, but you said that increased modularity predicted improved function,
2649
02:17:05.520 --> 02:17:11.879
especially with cognitive interventions. Psilocybin seems to induce fairly significant
2650
02:17:12.719 --> 02:17:16.600
increases in cross modal talk between brain networks, in other words,
2651
02:17:16.840 --> 02:17:17.879
less modularity.
2652
02:17:18.479 --> 02:17:21.799
So should we be concerned.
2653
02:17:22.319 --> 02:17:24.840
No, it's just it has to do with how we
2654
02:17:25.479 --> 02:17:29.159
make these measurements, and connectivity doesn't mean the same. You know,
2655
02:17:29.200 --> 02:17:32.879
there's different types of connectivity, and so I like to
2656
02:17:34.239 --> 02:17:36.959
when I think about connectivity, we talked about the connective
2657
02:17:37.000 --> 02:17:41.559
of brain state versus a brain trait. So when we're
2658
02:17:41.559 --> 02:17:45.360
talking about you being highly modular as a trait, that's
2659
02:17:45.479 --> 02:17:48.920
very different than what your modularity is like in different states.
2660
02:17:49.000 --> 02:17:51.799
It actually turns out you do when you do these
2661
02:17:51.920 --> 02:17:56.280
highly executive, demanding tasks, you get less mod You get
2662
02:17:56.479 --> 02:17:59.959
less modular because you have more your networks are communicating
2663
02:18:00.280 --> 02:18:03.639
with each other. So it's important to be for networks
2664
02:18:03.680 --> 02:18:06.319
to get less modular when it's a more demanding task.
2665
02:18:07.000 --> 02:18:10.719
But that's very different than than whether what's your you know,
2666
02:18:10.920 --> 02:18:14.399
what's your baseline modularity, because it's you've got to get
2667
02:18:14.479 --> 02:18:17.440
from your your you know where your baseline is to
2668
02:18:17.600 --> 02:18:19.159
this other state, and a lot of it has to
2669
02:18:19.239 --> 02:18:21.520
do is like going from one state to another, not
2670
02:18:21.799 --> 02:18:24.520
not so much sort of the absolute sort of differences.
2671
02:18:24.600 --> 02:18:25.600
So that's that's interesting.
2672
02:18:25.639 --> 02:18:27.600
I didn't know about those results, but it's interesting that
2673
02:18:28.360 --> 02:18:30.879
that it does affect sort of connectivity in that way.
2674
02:18:31.040 --> 02:18:33.399
I think the drugs that are going to be helpful
2675
02:18:33.440 --> 02:18:37.360
are gonna are going to promote sort of networks talking
2676
02:18:37.479 --> 02:18:40.360
to each other as opposed to networks not communicating with
2677
02:18:40.440 --> 02:18:40.799
each other.
2678
02:18:41.280 --> 02:18:44.719
In your clinic, do you ever combine drug therapies cognitive training,
2679
02:18:44.879 --> 02:18:48.479
and things like transcranial magnetic stimulation? Do you use stimulators?
2680
02:18:49.200 --> 02:18:52.079
Yeah, so I think, you know, I have a lot
2681
02:18:52.159 --> 02:18:56.120
of patients that I've referred for UH for its approved use,
2682
02:18:56.159 --> 02:18:58.760
which is depression. So I'm very excited about sort of
2683
02:18:58.879 --> 02:19:01.639
the work that's being done with it as a as
2684
02:19:01.680 --> 02:19:04.760
a for depression. But we haven't really had any improved
2685
02:19:05.239 --> 02:19:07.760
anything that's been for you.
2686
02:19:07.799 --> 02:19:08.600
Know, for cognition.
2687
02:19:08.840 --> 02:19:11.319
So there there are a bunch of studies and total
2688
02:19:11.399 --> 02:19:14.520
small studies where you can give transcrirent simulation in frontal
2689
02:19:14.559 --> 02:19:17.680
cortex and working memory improved, but they really haven't been
2690
02:19:17.719 --> 02:19:20.479
done in ways that are we don't know if it generalizes,
2691
02:19:20.680 --> 02:19:22.760
if it's if it's going to be how you know,
2692
02:19:23.000 --> 02:19:25.040
the way it's been done in depression in a way
2693
02:19:25.079 --> 02:19:25.719
that can really be.
2694
02:19:25.840 --> 02:19:28.159
But but again, it's just a matter of doing it.
2695
02:19:28.280 --> 02:19:29.479
I think it will be part of.
2696
02:19:29.559 --> 02:19:33.719
The things we do, drugs, TMS and all the other
2697
02:19:33.760 --> 02:19:35.479
things we've talked about. It's not just going to be
2698
02:19:35.840 --> 02:19:38.360
one one thing. And it gets back to networks, right.
2699
02:19:38.680 --> 02:19:43.000
What this is doing is really changing how nodes, you know,
2700
02:19:43.120 --> 02:19:45.840
the the interaction of regions. It's not about sort of
2701
02:19:45.920 --> 02:19:49.760
just increasing or decreasing activity in some mysterious part of
2702
02:19:49.760 --> 02:19:52.000
the brain. It's just sort of restoring the balance of.
2703
02:19:52.079 --> 02:19:53.520
A of a of a network.
2704
02:19:54.319 --> 02:19:57.319
Well, Mark, I I just really want to thank you you.
2705
02:19:58.360 --> 02:20:02.479
You're gonna given us an amazing tour of basically five fields.
2706
02:20:02.520 --> 02:20:06.120
I threw a lot at you, you know, as a neurologist.
2707
02:20:06.319 --> 02:20:09.559
But the way I'm I'm slightly reluctant to do this,
2708
02:20:09.680 --> 02:20:13.040
but I'm gonna tell you a joke that was told
2709
02:20:13.079 --> 02:20:17.680
to me, so that they are these people stranded on
2710
02:20:17.760 --> 02:20:23.280
an island and they're they're really stuck and they're running
2711
02:20:23.319 --> 02:20:26.920
out of resources. And by the way, this joke was
2712
02:20:26.959 --> 02:20:31.159
told to me by a physician, and all of a sudden,
2713
02:20:31.760 --> 02:20:35.159
this hot air balloon comes over and they're like, oh
2714
02:20:35.239 --> 02:20:37.319
my goodness. So they start they write help in the sand,
2715
02:20:37.399 --> 02:20:42.920
and they you know, and hot air balloon directly over them,
2716
02:20:43.479 --> 02:20:48.959
descends almost, you know, almost to them, and and then
2717
02:20:49.000 --> 02:20:51.879
someone in the hot air balloon says, you know, I'm
2718
02:20:51.920 --> 02:20:55.040
doing the measurement, and it's exactly seventy six feet down
2719
02:20:55.120 --> 02:20:57.760
to those people. And then the hot air balloon takes
2720
02:20:57.799 --> 02:21:00.280
off and goes away, and the people on the beach,
2721
02:21:01.120 --> 02:21:04.280
one of them is a physician. In egos, those were neurologists.
2722
02:21:06.079 --> 02:21:08.840
I tell that joke because that was the old school
2723
02:21:08.959 --> 02:21:13.559
view of neurology that neurologists were great at describing things,
2724
02:21:13.760 --> 02:21:16.799
talking about the terrible conditions they could observe in great detail,
2725
02:21:17.319 --> 02:21:21.680
but that they did not do anything about it. You,
2726
02:21:21.920 --> 02:21:24.440
on the other hand, and I'm guessing others in the field,
2727
02:21:25.040 --> 02:21:28.760
but certainly you have proven today that that joke.
2728
02:21:28.639 --> 02:21:29.600
Needs to be revised.
2729
02:21:29.639 --> 02:21:33.079
Whereby there's one, at least one neurologist who cast a
2730
02:21:33.200 --> 02:21:36.360
line down and shimmy's down and assists them and pulls
2731
02:21:37.200 --> 02:21:42.079
those stranded people on the island up to the balloon.
2732
02:21:42.159 --> 02:21:46.760
Because today you've described the underlying nature of some of
2733
02:21:46.840 --> 02:21:51.159
these things, like working memory deficits, traumatic brain injury, concussion, Alzheimer's, Parkinson's. Again,
2734
02:21:51.200 --> 02:21:53.280
I threw a lot at you, and you responded with
2735
02:21:53.879 --> 02:21:56.920
in thorough clear detail, but also a number of things
2736
02:21:56.959 --> 02:22:01.239
that clearly can assist in these in these in these situations,
2737
02:22:01.479 --> 02:22:06.000
such as from a cryptine mindfulness exercise and really as
2738
02:22:06.159 --> 02:22:09.680
an exploration of what can be done, interventions. And so
2739
02:22:10.719 --> 02:22:13.360
for all those reasons, and for tolerating this terrible joke
2740
02:22:13.440 --> 02:22:16.920
that I just told, I want to say thank you
2741
02:22:17.239 --> 02:22:21.040
because I've learned a ton, and I know the audience
2742
02:22:21.040 --> 02:22:23.840
has learned a ton, and much of what we've learned
2743
02:22:24.159 --> 02:22:28.159
has us looking in the directions of possibility to alleviate
2744
02:22:28.479 --> 02:22:31.680
these situations and as you point out, for the already healthy,
2745
02:22:31.719 --> 02:22:34.479
even to optimize brain function and health.
2746
02:22:34.719 --> 02:22:39.040
So for all of that, thanks for sliding down the
2747
02:22:39.120 --> 02:22:40.319
rope to the to the island.
2748
02:22:41.360 --> 02:22:43.040
Well, i'd say, you know, on behalf of all the
2749
02:22:43.079 --> 02:22:44.479
neurologists in the world, thank you.
2750
02:22:46.280 --> 02:22:49.559
We're appreciating what we do. It's just so important to
2751
02:22:49.680 --> 02:22:52.319
try and get this message apart. Like I said, you know,
2752
02:22:52.440 --> 02:22:55.479
with patients, we just try to have them understand what
2753
02:22:55.879 --> 02:22:57.840
it is that they're going through. And I think today
2754
02:22:58.000 --> 02:23:00.600
patients have to really be advocates for them selves, and
2755
02:23:00.719 --> 02:23:02.920
so I think the more they learn about all of
2756
02:23:03.040 --> 02:23:04.920
these possibilities.
2757
02:23:04.639 --> 02:23:07.399
The more they can go back to their doctors or
2758
02:23:07.799 --> 02:23:10.559
whoever try and ask for you know, what about this?
2759
02:23:10.719 --> 02:23:13.159
What about that is? Do you think this would help me?
2760
02:23:13.280 --> 02:23:15.799
Because we have to be advocates for our own health
2761
02:23:15.959 --> 02:23:18.000
and the only one we're going to do that is
2762
02:23:18.159 --> 02:23:22.440
just make people understand what it is that the possibilities are.
2763
02:23:22.719 --> 02:23:24.360
So thank you. It was a a lot of fun.
2764
02:23:24.639 --> 02:23:25.319
It's a great time.
2765
02:23:25.680 --> 02:23:28.559
Well amen to all of that, and hope to have
2766
02:23:28.639 --> 02:23:30.840
you back again. Thanks so much, You're welcome.
2767
02:23:31.639 --> 02:23:34.159
Thank you for joining me for today's discussion about the
2768
02:23:34.200 --> 02:23:37.879
brain mechanisms of cognition and memory and how to optimize
2769
02:23:37.959 --> 02:23:41.520
cognition and memory with doctor Mark Desposito. To learn more
2770
02:23:41.520 --> 02:23:44.319
about doctor Disposito's work, please see the links in the
2771
02:23:44.360 --> 02:23:47.159
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2772
02:23:47.200 --> 02:23:50.879
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02:23:51.000 --> 02:23:54.280
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02:23:54.319 --> 02:23:57.079
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02:23:57.159 --> 02:23:59.000
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02:23:59.079 --> 02:24:02.159
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02:24:02.200 --> 02:24:04.920
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02:24:05.000 --> 02:24:07.840
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02:24:07.879 --> 02:24:10.559
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02:24:10.600 --> 02:24:13.239
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02:24:13.280 --> 02:24:15.200
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2782
02:24:15.399 --> 02:24:16.879
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02:24:17.159 --> 02:24:19.479
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02:24:19.559 --> 02:24:23.639
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02:24:30.520 --> 02:24:32.959
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02:24:33.159 --> 02:24:35.319
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02:24:35.360 --> 02:24:38.520
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02:24:38.680 --> 02:24:41.760
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2801
02:25:15.200 --> 02:25:17.639
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2802
02:25:17.840 --> 02:25:22.479
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2803
02:25:22.879 --> 02:25:24.440
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