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

welcome to the huberman Lab podcast where we discuss science and science-based tools for everyday [Music] life I'm Andrew huberman and I'm a professor of neurobiology and Opthalmology at Stanford School of Medicine my guest today is Dr and Professor Mark despasito Dr Mark despasito is a neurologist and a professor of neuroscience and psychology at the University of California Berkeley he is a world expert in the brain mechanisms controlling executive function and memory executive function is the way in which we are able to designate and carry out specific cognitive strategies and it is fundamental to every aspect of our daily lives and because so much of being effective in daily life involves using specific context relevant batches of information in order to understand what to do and when and what not to do and when and to come up with strategies that are very adaptive for us to move forward in the context of relationships work school and Athletics and on and on there's really no separation between executive function and memory and today Dr desposito explains the neural circuits controlling executive function and memory how they interact the key role of dopamine in executive function and something called working memory and teaches us ways to optimize executive function and memory that is how to optimize cognitive function in addition to discussing how to optimize cognitive function in the healthy brain today's discussion also centers around how to restore cognitive function in disease or injury conditions that deplete executive function in memory such as traumatic brain injury concussion Alzheimer's Parkinson's and attention deficit disorders Dr desposito shares with us research findings both about behavioral and pharmacologic strategies to enhance executive function and memory by the end of today's discussion you will have learned from Dr despasito a tremendous amount about the modern understanding of cognition that is thinking and memory and the carrying out of specific cognitive strategies you will also learn a tremendous amount about how to optimize brain function and brain health before we begin I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford it is however part of my desire and effort to bring zero cost to Consumer information about science and science related tools to the general public in keeping with that theme I'd like to thank the sponsors of today's podcast our first sponsor is Maui Nei venison Maui Nei venison is the most nutrient-dense and delicious red meat available I've spoken before on this podcast and there's General consensus that most people should strive to consume approximately one gram of protein per pound of body weight now when one strives to do that it's important to maximize the quality of that protein intake to the calorie ratio because you don't want to consume an excess of calories when trying to get that one gram of protein per pound of body weight Maui Nei 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sleeping environment and that's what eight sleep allows you to do it allows you to program the temperature of your mattress and sleeping environment such that you fall and stay deeply asleep easily and wake up each morning feeling incredibly refreshed and energized I've been sleeping on an eights Sleep mattress cover for almost 3 years now and it has dramatically improved the quality of my sleep if you'd like to try eight sleep you can go to 8sleep.com huberman to get $150 off their pod three mattress cover eight sleep currently ships in the USA Canada UK select countries in the EU and Australia again that's 8sleep.com huberman and now for my discussion with Dr Mark desposito Dr desposito welcome hi Andrew thank you so much for inviting me I'm really looking forward to our ation yeah you may not remember me but I remember you when I was a first year graduate student and uh you showed up at Berkeley one of the first people to really bring functional Imaging of the human brain to Berkeley bring a neurology and a clinical um emphasis to the Neuroscience studies there and it's really just um blossomed and it's been a real thrill for me to see all the Magnificent work out of your laboratory over the years and I know you also still see patients so the topics that are of interest to you I know are of great interest to our audience maybe we'll just start off with a few of the basics and um do a little functional neuro Anatomy lesson for folks not to scare anyone don't worry this will be accessible to everyone and just talk about the frontal loes and prefrontal cortex and a little bit of what those structures do because many times on this podcast I've said okay the neural real estate right behind your forehead is involved in context and planning Etc but you're the real expert here um how should we think about what the frontal lobes do and and their various roles in health and disease yeah so there's four loes there's a frontal loes parietal temporal occipital and the frontal loes probably take up more do take up more territory than the other Lo probably about a third of of the uh cortex and within the frontal loes uh I I don't I'm going to use sort of frontal loes probably in our conversation a lot but what I really mean is the prefrontal cortex So within the frontal loes there's also Mo areas that important for motor function as well um but when we're talking about the frontal loes and talking about it's you know involvement higher level cognitiv abilties real talking about the prefrontal cortex and this is what's considered sort of the highest level of Cortex in the brain and so yeah when you think when you think about it people assign it all sorts of functions almost every function you think of people have sort of put into the frontal lows but I think what we've all kind of uh moved towards is this idea of executive function this abil this ability to to plan to organize uh to really transfer our thoughts you know into an action and really to be guided by goals and and intentions and not be kind of take you know kind of ruled by sort of just automatic behaviors a word we use in cob ner science is called cognitive control so C control executive function is what we attribute to the frontal L and so you can think of it as you know the CEO of the brain or the uh you know or the conductor of the orchestra really the part of the brain that's that's really controlling the the the rest of the brain so yeah if you had to choose which part you wanted to not leave home it's your front it's your frontal loes speaking of which um what are some of the uh symptoms of mild frontal lobe damage um and severe frontal lobe damage a damage brought about either through uh neurod degenerative disease or physical injury I know we're going to talk a bit about both today or a lot about both um but how would lack of executive function uh show up um um maybe on in kind of a subtle level yeah I mean at first I should say is that it it shows up all the time because when when uh and and frontal lobe behavior is probably much more prevalent than than we realize certainly we think about it when you have a brain injury to the frontal Lopes and there's lots of neurological disorders like stroke and traumatic brain injury and Alzheimer's disease that can affect the frontal lobe and there's a number of you know psychiatric disorders obsessive compulsive disorder and schizophrenia and depression that are thought to be frontal L dysfunction but when you're sleep deprived and when you're stressed and just normal aging the frontal loobe seems to be the first system that's affected because it really is involved in the highest level so when we're having a bad day when we're having difficulty sort of setting priorities when we're having difficulties achieving the goal that we've set out when we get distract you know when we get distracted um you know when we're not able to sort of adapt and be flexible these are all the type of things that are reflect that our frontal loes are not functioning optimally approximately what age does the frontal lobe circuitry uh come online so to speak I mean when I see a baby uh babies can Orient their eyes towards things but they're rather reflexive in in where they'll Place their eyes but um by time kids are three or four they can certainly you know play with blocks or interact with other children or their parents but it seems that you know full functionality the frontal loaves is it's really gradual at least that's my non-clinically trained assessment you know yeah I mean it's a really tough question to know when they're fully develop because these studies haven't been done when MRI was introduced and we were able to sort of image the brain in a non-invasive way uh then studies did start to come out trying to sort of map out at what age say your frontal LS fully develop and it seemed like it was early into your your 20s um you know I always say that it's not surprising that you can't rent a car until you're 25 that the insurance companies knew before n scientists did as to when your frontal lows have you know when your decision-making skills at their highest and so that's probably about right into your 20s um is probably before your frontal loes are fully developed and it's really interesting question is why why do it takes so long it's the area of the brain that takes the longest to develop and why is that and I think there's a reason I think that this sort of slow development frontales allows us to to explore allows us to to think about novel ways of solving problems allows us to take in the world if they were shut off earlier uh it it would lead to maybe a much more sort of rigid kind of you know less flexible kind of uh behavior that that we'd seen things so I so I think that that it helps to be uh it take a long time to develop but also it obviously leads to some problems sometimes in adolescence as as as we see sometimes can one see a lack of frontal L maturity in just the sheer number of physical movements that a child makes um so for instance in a classroom of uh you know let's say um you know fourth graders um oftentimes there'll be a range of uh a parent ability of kids to sit still or to listen um do we think that the kid that's having a hard time focusing and listening to instructions or steadying their body when they're told to sit still um I don't know if they still tell kids to sit but they were telling me to sit still when I was a kid um is that um somehow reflective of a you know slightly lagging frontal frontal L function um and maturity whereas that you know the the kids that can sit you know still and stoic and focus does that mean that they're a little bit more accelerated along that trajectory yeah it's hard to say I mean the frontal lobe is B is a big territory and we can get into it but there's you know the frontal L probably has 25 different sub regions within it and and so grossly we think about the frontal loes as the lateral portion of the frontal loes which is involved in these executive function probably supports these exective function abilities but then we've got another part of the frontal loes called the orbital frontal cortex which is probably involved more in Social and emotional Behavior so you know when we think again when we think about frontal L behaviors uh they kind of you have to break there's so many different type of frontal behaviors so that type of behavior which may be involved in sort of being able to inhibit you know your motor movements or maybe not being distracted May reflect that that system is a little bit delayed but it could be that another system the one that's involved in planning and organizes you know it's more developed and I I do think they they develop at different trajectories so with the frontal loes essentially um serving an executive or CEO type function goal directed Behavior intentions cognitive control uh these are the terms you used um where are the rules what do the rules look like you know when I think about brain function which I've spent a lot of my life thinking about we think about chemical and electrical signaling between neurons different neurons communicating more or less at a given moment reflecting some sort of circuit as we call it and then some Behavior or some decision comes out and if I for instance um have to get my driver's license renewed soon so if I go to the Department of Motor Vehicles what a lovely experience that is um the moment I get there that i s of lock into a certain rule set um when I'm home I'm in a different rule set when I'm in with my friends versus when I'm with my parents different rule sets and it seems that the frontal loobe is really good at um drawing on context based on knowledge of where one is um and then coming up with kind of algorithms that are appropriate or inappropriate to run in that context but what is the nature of these algorithms are they um of the okay shut down all um cursing in this environment um okay you're free to just quote unquote be you I mean when when it really comes down to it it has some interesting philosophical aspects too because uh just be yourself be authentic be vulnerable you know all these things make sense but of course one needs to be appropriate with the context so how how do does this work like what what is the what are the algorithms how how does this work right because because that's a pretty common example of our patients that they they don't follow the rules um they they you know if you're sitting in a someone's the doctor's office and the phone rings you you you know not to pick up his phone but the patients don't and they they may pick up the phone there's there's this Dr L who's a a neurologist from France published these beautiful papers in the 80s of all these things that patients did that just that broke the rules and and so and BR just kind of pulled to the their environment without having any context to it if he put a pair of glasses on the table uh and didn't ask going to put them on they would put them on even if they had a pair of glasses on already or he took them to their apartment and they saw the bed and they jump into the bed and go under the covers or he saw he had a nurse and she he put a blood pressure cuff there and she picked up the blood pressure cuff and just started taking his blood pressure again not asking him to do any of these things and so they they they just don't follow sort of the social rules but they're there they they haven't lost rules if you ask these patients was that the appropriate thing to do they'll say no they know it's not they know it's appropriate yeah they say no I'm not supposed to answer your phone but oh wow so they know better but they can't control the impulse exactly so it's it's it's so it's not a breakdown that the rules disappear it's that they can't apply the rule they can't apply the rules Pro properly and and and that's true for a lot of PA patients even with kids you know you tell them uh don't have anything to eat before dinner because we're having dinner and then they're sitting there having a sandwich and you say what did I just tell you you said well don't eat but I'm I'm hungry right as another sort of example sort of the frontal Lo's not completely kind of developed so when I think about rules I I think about the brain you know the brain processes information obviously but it also stores information the most important thing it does is store all sorts of information all over the brain and I think what the frontal lobes do is they store rules and what's interesting uh about the way it stores rules they seem to store the rules in a hierarch arcal fashion um and what I mean by that is that there's different levels to rules I like to give the example of uh playing golf I tell a story a lot about my good friend bob Knight when he hits a ball into the you know off into the woods and he has to try and hit the ball out of the woods he's holding on to all different levels of rules on how to successfully get his ball back towards the green so the most simplest one is just like where you know where is the FL you know I've got to maintain the uh orientation to get to the flag you know so he's holding that he also at a higher level rules he knows that if he kicks the ball it's a penalty so he's not going to do that right and then another higher level rule might be if I just keep doing this you know then this is going to be healthy for me so he's storing all this information at sort of at different levels of hierarchy and he's apply he's applying it to ultimately achieve this very simple Act of or not so simple Act of of hitting the golf ball so yeah so I just I think about sort of the frontal cortex is able to call upon the rule in the appropriate context and if you don't have your frontal loaves it it it doesn't get pulled up properly and those rules must be learned right they it there's no way I can imagine that one can be born into the world with these rules sets intact um I think about the the two marshmallow experiment that's sort of famous now um where kids are offered to eat uh one marshmallow right away or right defer and get two marshmallows these adorable videos of theid the strategies they use like Turning Away poking the marshmallow and you know there's some debate uh ongoing as to whether or not uh success or lack of success in deferring to the two marshmallow reward is um predictive of of other things in life but leaving that aside um am I correct in assuming that that task is a frontal lobe task the kids are given a novel rule you can have one marshmallow now or wait um patiently and then uh with and overcome the craving for that one marshmallow and then you'll get two um and presumably that um that experiment is engaging the frontal loes and you know we can only speculate but um some kids are able to defer some are not um and I can imagine that at that age there's a lot of neuroplasticity um strengthening and weakening of Connections in the brain on in an experience dependent way so does that mean that um children and perhaps adults as well can train up their prefrontal Court cortical abilities to strategize and defer in a way that's adaptive absolutely I mean definitely you can learn strategies to not only sort of learn rules um but but how to apply goals when when you start to think about that task in particular some of it has to do with sort of maintaining a goal and and maintaining a goal at different you know time scales right and children tend to sort of act on goals that are much more short on a shorter time scale you know I'm going to have the sandwich right now because I'm hungry as opposed to wait till till dinner which is a longer longer term goal and so yeah this default to sort of the shorter you can you can learn that maintaining a longer type goal uh can be much more beneficial uh than than the short-term goal even though it doesn't seem obvious and we all learn that right we as we as we get older most us we keep our eye on the ball of sort more long term goals and that's very predictive of how successful we can we can be the farther out we can maintain a goal and that's what the that's what the prefrontal cortex does it maintains goals and then applies those goals and if you don't apply them then you lose you know then you then all of this executive function breaks down do you think that these algorithms and rules that the prefrontal cortical circuitry can learn and indeed does learn can generalize so for instance when I my first year of college was the disaster uh for reasons that aren't interesting right now but then when I came back my sophomore year really spring of my freshman year I was like okay it's on it was I had to rescue myself and so one of the things I used to do was I would study um and I would set a timer so I refuse to get up even if I had to use the the restroom very very badly I would um set up all sorts of Behavioral constraints um and I like to think that I was building up my prefrontal ability to refocus on the material and fortunately for me there were no smartphones back then it was much easier internet we had email but no real internet browsing to to speak of and I like to think that the I sometimes call it uh and this is terrible um to call it this because it's not uh nearly exhaustive of the underlying function but I call it sort of like lyic friction it's like there's this friction that one feels mentally like you want to get up you want to use the restroom you want to eat something you want to call a friend but you stay focused on the task at hand do you think that that business of quote unquote staying focused on the task at hand can generalize because of the sensations it generates in the body and then you oh this is familiar this is just like studying but in a different context one is one stays focused or do you think that the prefrontal cortex is is so context specific that it needs to learn a Ru the rules for every individual situation and then this has all sorts of implications for Behavioral restraint and focus and attention deficit so uh if you could just speculate um I know a number of people are interested in how they can be more focused and people often defer to like what supplement what drug okay that those are interesting conversations but I think ultimately we're talking about neural circuitry yeah I mean it absolutely can generalize it that's been a frustrating thing into trying to develop what we call cognitive therapy where we we teach we try to improve someone's memory ability or we try to improve someone's executive function ability the the disappointing early results was always that yeah they get very good at the task that you've trained them at but it doesn't seem to generalize to anything else so if you teach them a you know a task they can do amazing things like match a finger to a color to a shape and put together all sorts of rules and then and they're really good at that task very quickly and then nothing's really changed in their real life but but I think we've learned on how to sort of on how to try and make it uh translate to real life and and so for example there's there's a therapy called goal Management training which is developed um by Brian LaVine and colleagues at the rotman Research Institute of Toronto where they've been very successful in teaching uh patients how to improve your executive function uh and how to make that translate into your real world but it's it's very hard work it's it's very therapist driven it requires um it requires a series of of trainings for example people learn uh they develop individual projects like planning a meal or planning a family vacation or planning a podcast and then they work through what's involved in that sort of very specific project how you how you stay focused how you don't just get distracted how you keep your eye on the ball how you break it down to subg goals how you um you monitor what you're doing how you don't let anxiety and procrastination get involved but it's a it's a very active sort of process but when you add all that to it in a very disciplined way over the course of many hours and many weeks it does translate patients and individuals to say yeah I'm just better at doing things I mean the whole goal is to do things right and and I'm just better at it I don't know what it is but I'm I'm not just better at what you taught me I'm just better at other things so I do have a lot of hope that these kind of therapies will generalize to the you know to people's real life I throughout the term lyic friction again not a technical or clinical or official term in any way but just a way to kind of capture um some of the interactions of the frontal cortex with other circuitry I mean there's far more um involved in ation and challenges focusing than the lyic system but it's it certainly is involved um when thinking about the frontal cortex I often think about its connections with other areas of the brain so maybe we could talk a little bit about those connections and and in particular the connections from the frontal cortex to let's call it um circuitry that controls reflexive behaviors um what are what is the nature of that circuitry and um can we make any general statements like does the frontal cortex really serve to um provide a quieting um suppressive function on reflexes or is it more of an Orchestra conductor where it's saying okay A little bit of that and a little bit of that um and then what's what comes out in Behavior or speech is something that looks very organized but is actually the the the reflection of a lot of selective filtering yes I mean the prefrontal cortex what's so fascinating about it is that it I would say it connects to every part of the brain uh cortex and the subcortex and almost every part of the brain connects to it so that I mean that right there tells you it's a pretty important area and it has to if it's going to be in this CEO you know conductor type experience uh role and so it's in this privileged position just anatomically so that that gives us great insight to how important it is and so it is connecting and then of course we could talk about it how it's connected to the body as well how it controls heart rate and respirations as well well so it's not just just the brain so um but it's really interesting like like you said is is it really just sort of maintaining telling you what's relevant and what's not relevant or is it allowing you to switch I I think it does all those things it it it definitely what we call sends these top- down signals it sending signals to the other brain about what you should be paying attention to and what you shouldn't be paying attention to so for example if you we've done studies with functional Imaging where we have them look at pictures of faces and scenes and that lights up the back of your brain your visual cortex has areas that are can process faces and process scenes and um but sometimes we have you just want to pay attention to the faces and not the scenes and other times we want you to pay attention to the scenes and not the faces well you know even though it's getting the same bottom up visual input the prefrontal cortex will will show greater activity to the relevant information it it'll it'll sort it's sending a signal say pay attention to the faces ignore the scene and uh or vice versa so it's it's directing all of this information that bombarded with to what's what's relevant but at the same time it's also uh allowing us to switch if if that we now have to go switch to another task it says okay this is not important now we're going to move over to this this other other task so there's many different components of how it can you know how it can kind of control Behavior but it does all of these things in this incredible way that we still don't completely understand but we know that's the source of of all of this control is coming from the prefrontal cortex I'd like to take a brief moment and thank one of our sponsors and that's ag1 ag1 is a vitamin mineral probiotic drink that also contains adaptogens I started taking ag1 way back in 2012 the reason I started taking it and the reason I still take it every day is that it ensures that I meet all of my quotas for vitamins and minerals and it ensures that I get enough Prebiotic and probiotic to support gut health now gut health is something that over the last 10 years we realized is not just important for the health of our gut but also for our immune system and for the production of neurotransmitters and neuromodulators things like dopamine and serotonin in other words gut health is critical for proper brain functioning now of course I strive to consume healthy Whole Foods for the majority of my nutritional intake every single day but there are a number of things in ag1 including specific micronutrients that are hard to get from Whole Foods or at least in sufficient quantities so ag1 allows me to get the vitamins and minerals that I need probiotics prebiotics the adaptogens and critical micronutrients so anytime somebody asks me if they were to take Just One supplement what that supplement should be I tell them ag1 because ag1 supports so many different systems within the body that are involved in mental health physical health and performance to try ag1 go to drink a1.com huberman and you'll get a year supply of vitamin D3 K2 and five free travel packs of ag1 again that's drink a1.com / huberman you mentioned connections between the prefrontal cortex and the body um that's the first I've heard of that um and I'm not challenging that to the contrary I'm just intrigued by it um I'm aware that the hypothalamus and some of these deeper brain structures associated with more um let's call them primitive drives um temperature regulation uh hunger Etc connect to the body but uh what what's the nature of some of the connections with the front to the body yeah I was just sort of talking in terms of of our knowledge of how you know changing on one of your podcast you talked about how TMS to the prefrontal cortex can slow heart rate so I meant in that in that sort of way got it that that that yeah by by that by influencing cortical function will obviously we can influence uh organs like the got it so through some intermediate stations yes yeah I mean it's you know not to um not to be hyperbolic but I mean it seems like the prefrontal cortex here we referring to as the frontal loes um are essentially the seat of what makes us human and What Makes Us functional or dysfunctional in a given context right I mean uh I recall there's a syndrome cluver buy syndrome which has some vague um uh similarities to how you describe frontal cortex damage but there as I recall humans or animals um with that syndrome will act in a way that's not appropriate to context but more inappropriate like they'll they'll try and eat a ceramic cup or Draw with a piece of paper which obviously won't work it seems like with the frontal cortex it knows that a pen is for writing it just the person might say yeah I know I'm not supposed to write this but I'm just going to or write with it but I'm going to take your pen and write something inappropriate with it but it it's not that they people forget that there's a that it's a pen so it seems like it's drawing on um so rule sets but that something's intact it's like it's not like cluver buy syndrome where um like animals and people can try and like mate with inanimate art objects um which is one of the more Salient um symptoms I'll never forget that never forget that from from my cognitive Neuroscience course which you taught by the way um just throw that in there so yeah so how how should we think about this and here I'm trying to get at a kind of a broader understanding of brain function and context specific behavior um it so frontal cortex is like super sophisticated um but it doesn't have all the information right it seems like someone without a frontal cortex probably knows that you write with a pen you don't write with a piece of paper yeah I I think it's you know we think about it as it's you know the frontal CeX allows us to take thought and move it towards action and there's this disconnect between the knowledge and and action and the separation of action from knowledge and I guess I can reflect on my patience you know when I I've seen a lot of patients with damage all over the brain and all of the families of patients who have frontal Lo injury always say the same thing they're they're just no longer that person they're no longer my spouse they're no longer my best friend they're no longer my father just something they can't put it into words but they're not them anymore there's something has changed whereas if you talk to a patient with brok as aasia who has this inability to speak they can't get any words out you know this is a devastating problem they're still the same person they they they their personality hasn't changed they they feel the same person they just can't speak the way they get around in the world is different or if you take a patient with prosopagnosic which is uh this inability to recognize faces of course the way they navigate around the world is is is difficult and it's not the same but they're still the same person so there's something really special about the frontal cortex that allows us to be as you said sort of who we are and that's the difficult part like how does the frontal Lopes allow us sort of take um take who we are and translate that into knowledge so we're not I guess in other words saying just just having knowledge isn't what makes us who we are right it's to be able to take that knowledge and and and present it in a way that allows us to live life based on our intentions and our goals and our desires so much of things like stoic philosophy and um and even online Wellness culture are about um having routines um you know overcoming reflex by just having recipes scripts to follow each day um I certainly try to have my mornings be as what I call linear as possible and I find it's much easier in the earlier part of the day to just decide here's what I'm going to do write out a list do things in a certain sequence if I don't do that I go nonlinear as I refer to it and we'll get distracted and things of that sort but um earlier you mentioned sleep deprivation can impair frontal Lo function it does seem that um as the day progresses and certainly in the middle of the night it just becomes much harder to um control our our thinking maybe even our Behavior but um and certainly our emotions is there a frontal lob uh regulation of emotional states as well I know you have some recent work on this so i' love to hear more yeah yeah I mean as I was saying earlier the frontal L is a big place and and half of it is involved in these high level executive functions but the other half of it is in is part of the lyic system or that we call it the paralic system that's involved in Social and emotional behavior and so uh there's this intimate back and forth between these two areas of the cortex if you have just damage to these frontal to these areas that are kind of in the overal frontal lobe you will have many different impairments that we would call sort of social or emotional impairments and they're executive function will be quite normal and then you'll have the the opposite where patients with the lateral damage will have executive functions but they seem emotionally intact but but you know in real life when we have both these intact they're they're communicating with each other so right emotion and context and is going to influence our executive function we make bad decisions in stressful situations or situations we're not comfortable with it's it's where we might make a better decision if it's a quiet you know kind of quiet place um but it is something that we can I think you you're right you can you can sort of get into a routine and learn how to do things you know if you have very much planned out but what's so unique about us is how we can be flexible and adaptable right when when something novel comes up or there's something something unexpected comes up we can adapt to it and that's really what the frontal cortex is really important for um not just sort of making these plans routines and setting all the rules but being a when things don't go right how to how to write the ship right I will never ask you to um demonize technology um I certainly use a a smartphone um from waking till sleep um generally not in the middle of the night if I can avoid it uh and I generally avoid it but I'm trying to take what we've discuss this far and superimpose the the notion of smartphones and ask what are the rules what are the algorithms that we're learning when we use these devices and I'm not calling them adaptive or maladaptive they're clearly here to stay they've assisted in medicine I'm sure it makes it easier for doctors to communicate on the on the ward and and for um clinic and it's so useful right but contained in this small device um there are things like uh for instance text messaging where unlike 20 years ago we can have four or five different conversations very quickly while boarding a flight um there's a task switching element that was just not present in our life um prior to that um social media in particular this notion of being able to scroll so move if we really step back from this move one's thumb and access hundreds if not thousands of video content from dist which Each of which has a distinct context um and so I have to imagine that kids and adults have frontal cortices that are learning these rules and the rule is move your thumbs stay engaged emotions either positive veilance emotions or negative emotions I mean it's it's a fairly limited um landscape there when you really think about it but but the algorithm that's learned is to me doesn't seem exportable it doesn't help me prepare for a podcast at all I know that for sure doesn't help me go for a run doesn't help me listen with more focused attention to a family member or a friend or a significant other um it may make me more empathic or more angry I you know we can we can speculate but um again with no with no intention of demonizing social media does it seem that the the algorithms that are being run in our brain I mean are they neutral are they positive are they negative should we be worried um it doesn't seem like they translate to much else they they W I can't see a way in which they help us be better people in other domains whereas reading a book line by line and then going back oh I didn't even remember anything from that page going back line by line um playing a game of squash or something like that there I can see the real value of the rule sets that generalize yeah I mean I can you know just historically I grew up in a world when there was no smartphones as a resident and and so one of the most difficult things I do in practice is have to take care of patients in the emergency room and there's a real emergency someone's having gun control seizures or they're having a stroke and you know doing this back in the 80s or 90s and early 2000s when you went down there and you didn't have any smartphone you you could only rely on what's what's in your head and I could say now having the smartphone it hasn't it doesn't help me at all I I never you know it does not help me at all in making the kind of decisions that I have to make in the emergency room I'm I'm trying to decide you know what what what's the problem here what's the differential diagnosis what how should I treat it I'm just trying to make very going through an algorithm like you said in a common sense way and there's nothing on my phone that I can turn to to help me do that it has helped with giving me knowledge like back in the day I had to remember what the Dilantin dose was and have that in my head or go look for the piece of paper in my pocket and so I can quickly pull up you know I guess I'm a little bit you know there's information that I can access that I don't have to worry about keeping every single dose in my head or keeping everything in my head just facts in my head but uh outside of that there's nothing I can turn to that it's it's making me you know better making me make better decision so I I don't even need my cell phone I don't go searching my for my cell phone if I'm going to go to mer room or going to take a take a phone call so I don't see how it's helping sort of make your frontal Lo it can't be your frontal loes I mean it's another way of saying it but but on the flip side can it help you optimize frontal low function technology certainly it can we can maybe talk about it later there there certainly that's one way to get learn strategies is through a through a device that that's easily accessible and uh you know to you as opposed to a book or or having a therapist uh in your house yeah I suppose I worry that um too much of my time and other people's time and especially young people's time is um engaging in a algorithm that does not um generalize for adaptive Behavior elsewhere and and by comparison you know like a a game of soccer with friends or something right it's social social media is social um it's physical social media is not physical but we'll we'll rule that that portion out but there's a rule set um there's gold directed behavior um presumably some of the things that happen in a game of soccer with friends translate to some other domain of life um because it's a single context game of soccer whereas with social media I don't know anybody that goes and looks at One account and that's it and absorbs the information maybe comments has an interaction and goes it's it's hundreds or thousands of contacts so is there any risk or perhaps benefit to being able to um get this very detailed portal into so many contexts per unit time I mean the the forebrains never had done that in the course of human history as far as I know yeah I mean I think there is a risk but what Pops to mind you know having kids is is watching them navigate in their cars to places totally dependent on on Google Maps um I I think you're probably old enough to remember real Maps where you didn't I still have one in my I still I love paper maps I love Maps right where you had to really figure out you know you you had to go to a certain place and you had to either look at the map or or or ask stop at a gas station and ask these these these skills were something that you learned and you developed and it was problem solving and and uh and that's all gone now I mean it's it's I I wonder even if sometimes if if uh people even know the direction they're going whether it's West North or what set they're in because they're just following the directions so I we we'll see I I just can't imagine that that learned skill is not going to be detrimental to us at at some point and generalize in the generalize in a bad way right as as opposed to a good way um so I don't I yeah it does it does definitely worry me but like you said there's nothing on the phone that helps you plan a podcast nothing that helps me in the emergency room nothing helps a professor when he's giving a lecture so I agree with you that that the sort of having your head buried in in a cell phone I'm not yeah it's I don't see it being healthy for your frontal loves let's talk about working memory um some years back but still now you use working memory tasks and experiments in your laboratory if you would um be so kind as to explain what working memory is and then I'd love to talk about um some of the work you've done exploring the role of dopamine in working memory um because this is so critical to everyday life and I know dopamine's a bit of a buzzword these days but um the listeners of this podcast anyway are are um pretty sophisticated in terms of knowing that dopamine is not just about reward it's about motivation and goal directed behavior and I think dopamine intrigues for a good reason that it does govern a lot of our you know quality of life so um what's working memory yeah I mean working memory it's interesting I started studying at about 30 years ago and I don't think I realized how important it was when I started but what we mean by working memor is this ability to hold information in mind uh when it's no longer accessible to us so if you tell me your telephone number and I'm have to put it into my phone you know it's no longer there you just told me but I'll hold it in my working memory until I can punch it into my my phone it doesn't have to be something that comes from the outside world I could hold up uh you know I can pull up my own if I'm filling out a form and I want to pull up my social security number can hold that in mind too until I put it down so um when you think about it it's a very important uh you know ability that we have that we do very flawlessly and what I've learned more about working memory is is the working part of it it's not just this passive holding information on mind but it's being able to do things with the information it's being able to um you know when we when we do a bath problem which we don't do that much now that we have calculators but if you do that in your head you're able to sort of manipulate the information and and do the different parts of the problem or even if you're you know you're trying to find someone in a crowd and you're holding on to some face you're able to hold that face in mind and cross check it and search and and so there's there's operations to working memory it's not just you know it's not just this passive maintenance so when we start to think about working memory in that way we start to realize how important it is for it's you know I think of it as the foundation for for cognition just think about reading comprehension you can't understand this conversation if you can't hold in mind what's going on you know earlier in the in the conversation or when you're reading a book you know remembering the sentence uh before it so it just predicts all these abilities that that allows us to to read to to uh plan to organize and all the sort of executive functions that we're we're doing right we have to hold in mind rules we have to hold in mind goals we have to hold in mind all of these things in order to carry out behavior um you know so it's it's it's it's really come a long way in terms of how people are thinking about it I I I know that uh Matt Walker said that like you know sleep is our superpower but I guess one way to sort of use this term while we're awake working memory is is really our superpower because it it allows us to to translate as we said sort of our knowledge into action by holding this information uh in mind as we're thinking about what we want to do if we're going to think about dopamine in the context of working memory is dopamine an accelerator on working memory is it a facilitator I mean what is dopamine doing for working memory and maybe we could talk a little bit about the circuitry um I've talked about dopamine before on this podcast but there's a good chance that some of the people listening to this haven't heard those episodes so maybe we could just quickly review the three major circuits for dopamine and the one that's relevant for working memory yeah let me start with the working memory the circuitry for working memory because one one of the important things about working memory is the other type of memory is is long-term memory it's it's you you can working memory shortlived it's only as long as you're able to rehearse it and then it disappears whereas what we call long-term memory if I remembering what you had for breakfast or your vacation this is information that's gets Consolidated and and gets put into a a more durable form that we call long-term memory and the interesting thing about memory is that these are separate systems everything from working memory just doesn't pass into long-term memory there're they're two completely different systems and and two completely different parts of the brain that seem to control it um so working memory uh the frontal cortex seems to be very important for working memory when when we are holding information in line the neurons the brain cells in the frontal loes are active and they stay kind of active as long as we're holding on that information and they're more active when the information is relevant um and if we uh we we get distracted they'll get less active so it kind of the frontal Loops kind of track your uh you know track TR the memory that you're holding in mind another important thing about the circuitry is that um if we're holding in mind say digits you know the phone number well that information is in your back of the brain and so the the frontal loes is sort of keeping information in the back of the brain active because it's connected to the visual areas it's it's able to sort of keep that information active and so what what we've learned is that there's not these buffers in the brain where oh you know if you're holding verbal information it's in this little buffer if you're holding visual information it's in another buffer the whole brain acts as a buffer and and the frontal lobe can call up any part of the brain and keep that part of the brain active as it's as it's you know as it's trying to hold this information in line so the mechanism for working memory is just this persistent neural activity within the frontal LS and so then the question is what does dopamine do well dopamine is one of the neuromodulators that are made in the brain stem and IT projects up to different parts of the brain there's a system that goes up into the into the what we call the basil gangula which is important for motor function and there's another dope neric system that goes up to the frontal loes and what was discovered was that if you deplete DOP mean a working memory drops you get a significant impairment and working memory if if you deplete dopamine and if you replace it uh then your working memory will be improved and so DOP mean seems to be a modulator to help this persistent activity stay persistent consistent uh you know during the time that you need to keep this information in mind am I reaching to far to draw an analogy between dopamine's role in working memory that is to keep information online and the other established role of dopamine which is for movement for the generation of smooth movement um as evidenced by conditions like Parkinson's where people lack dopaminergic neurons or have damage to dopaminergic neurons and have a you know challenges in generating smooth movement what I'm essentially asking is can we think of dopamine as facilitating physical movement through one circuit but also kind of mental movement thought movement and um I'm thinking about for those just listening and and not watching I'm kind of rubbing my um index and middle finger against my thumb just keeping something online um it's sort of a movement of thought or information and then you kind of Chuck it away and bring about the next information is that is that yeah I think that's a good way of thinking about it and one might wonder well how can do me be important for memory but also be important for movement and and it's really simple it's just that it's acting on different circuits the the the neurons that go to the motor areas that carry dope mean will will when dope mean is expressed there then and boosted there then it will be involved in movement and lack of dope mean in the basil ganging will lead to neurological disorders like Parkinson's disease that has severe movement uh difficulty but when it's acting in the frontal cortex uh and expressed in the frontal cortex then it's going to improve working memory so it's just it's just a the nature of where the circuits are where the DOP mean is that's that's allowing it to have different kinds of actions and that's all for all transmitters the reason why OS choline seems to be more important for long-term memory is because it it's projecting to the hippocampus which is we know is another area that's important for memory and that's why asine doesn't boost your working memory but DOP mean does and vice versa I'd like to take a quick break to acknowledge our sponsor element element is an electrolyte drink that has everything you need and nothing you don't that means zero sugar and the appropriate ratios of the electrolytes sodium magnesium and potassium and that correct ratio of electrolytes is extremely important because every cell in your body but especially your nerve cells your neurons relies on electrolytes in order to function properly so when you're well hydrated and you have the appropriate amount of electrolyt in your system your 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element.com huberman so drilling a little bit more deeply into the role of dopamine and work memory uh you did some really lovely experiments uh showing that if um people who have low levels of dopamine um increase their dopamine uh pharmacologically I think the drug that was used was bromocryptine um that working memory improves um conversely if one depletes dopamine pharmacologically dop uh working memory gets worse um but as I recall there was an important Baseline that is important because it really mattered in terms of the outcome meaning if somebody already had relatively high levels of dopamine in this circuit increasing dopamine further with bromocryptine didn't impart a benefit and might have even made their working memory worse so there's a kind of inverted us shape function to this um how does one know whether or not their Baseline dopamine is low medium or high Ergo how do they know whether or not that they would uh want to explore going about increasing dopamine through any number of different approaches right well most people probably have optimal dopamine but there's a significant percentage that probably have too little or maybe too much and it's unfortunately we can't measure it in the blood um there isn't a blood test that I'm aware of that can can measure uh do me because it's stuck in stuck in the brain um peripheral dopamine in the blood doesn't is not a good readout it's not a good readout yeah and and especially when you're talking about dope mean in in areas like prefrontal cortex and um so we don't have a good read out there there's there's invasive procedures like positron emission tomography where we can inject a radioisotope um and that tags DOP mean and then we can measure how much we can do a scan that actually shows us how much dope mean this scan was originally developed to show Parkinson disease that that you can diagnose Parkinson disease by showing that there's there's less DOP mean in patients that have Parkin disas by looking at this this scan um obviously it's invasive you're injecting a r isotope it's expensive and it's not something we could all do but we had used it to show that it correlates very strongly with your working memory capacity so how much information you can hold online if you can hold four or five or six letters when I do a a span task um correlated with how much do me we can see in the pet scan so that that would be a a way that we could do it um so if you were to read out a string of a few numbers or letters um and and I can remember all of those a few moments later um Perhaps Perhaps my Baseline dopamine levels are U moderate um in the in the normal range whereas if I couldn't keep that online um that might be might be reflective of lower Baseline dopamine levels is that right yeah it's a it's a very strong proxy for dopamine so if you're you're working Maring capacity is seven letters when or numbers when I say 437 1506 if you 43 get them all back pretty quickly you probably have more dope Baseline dope mean than than someone who has five they're so it's it's a proxy for measuring someone's open so that that's one way of do it and that's actually how we did it in our original studies we we actually um grouped individuals based on whether their capacity based on this behavioral measure was high or low and like you said those who were that can only hold five or six letters if we gave them bromo crype which was the Doper nergic Agonist we improved their working memory uh we got them into sort of an optimal level but but those who were already Pi we actually made them we were we got them worse and the moral of that story was that more is just not better we're trying to get people optimal and so the real question is is you know if we want to get people optimal like you were inferring you have to know what their do mean is where where are you on this inverted you curve another way of doing it it uh is through um a Genet through genetic studies so we have don't mean uh all neurotransmitters have to be broken down and re-uptake into the into the brain cell in order to be used again and there's different ways of doing it and some cells uh it gets transported back into the brain cell and other other places there's an enzyme that that breaks it down well there's an enzyme called compt uh that is breaks down dope being in the prefrontal cortex specific speically in a large percentage of individuals that enzyme is either overactive or underactive probably about 25% of individuals it's overactive and another 25% it's underactive so probably half the population now this is going to vary depend on other where you live and where you come from and things but it but but maybe half the population either has an underactive enzyme or overactive enzyme if you have an underactive enzyme then actually more dopamine sits around and you you actually have more dopamine than others and if you have an overactive enzyme it's the opposite so we've actually shown that if you now go and genotype people with a simple saliva test and figure out do they have this genetic what we call polymorphism where just one amino acid gets changed and the enzyme becomes either active or underactive we can we can do the same thing as as grouping them by their capacity those that have the low dope mean we will make make them better and those who have sort of Baseline High dope me will will make them worse super interesting um maybe we could talk about bromocryptine a little bit and I'm not encouraging people to run out and take bromocryptine um bromocryptine as you mentioned is a dopamine Agonist um relatively short acting yeah four five hours six hours so kicks in about 90 minutes after as I recall you saying I've never taken it um how do people feel when they're on bromocryptine I mean when I hear uh dopamine Agonist I mean there are a lot of illicit drugs like cocaine methamphetamine that are increased dopamine but then again chocolate sex and food increased dopamine but the kinetics the time course and the levels are different for each of those things um dopamine of course being a currency of motivation and reward not not um directly related to any one compound but um I would think that based on the data you just described that um and given the fact that there are a number of people out there with challenges in working memory attention task switching Etc that there would be a strong interest on the part of the pharmaceutical companies at least and certainly the general public um in things like bromocryptine to increase dopamine to increase working memory given it it is our superpower yeah I mean one of the most disappointing things to me in my career has been that pharmaceutical companies have not picked up on this idea that that we could improve cognition and very specifically improve C process with very specific neurom modulators the the discovery that depletion of dope mean and not other transmitters and pairs working memory was made in 1979 um when I heard uh Pat G talk about this as a resident I was just amazed that there could be a single transmitter can change a single Behavior I was seeing very complicated behavioral deficits and it just seemed impossible to me that there could be such a tight link between a single you know a single neurom modulator and a single cognitive process and just open the door for me that this really could be a incredibly Ben official therapy for for any anyone with executive function or frontal low function so but unfortunately there's never been a Pharm company that's tried to develop a drug for improving cognition to this to this day and they I mean it's crazy for several reasons one is that the data are clearly there uh two these drugs are already established it's not like they have to go through safety trial again that that's already been done but mostly because regardless of whether one is a fan of the pharmaceutical industry or hates it the pharmaceutical industry in principle can make a ton of money doing this so I would think that they'd be heavily incentivized to do it so why have they um Turned a blind eye on this I'm not sure I mean when I realized um that I could test these drugs in in healthy individuals that that they were s if I gave them in low enough doses they were safe and and I had so much experience of them in patience that I felt comfortable doing it um then I started asking pharmaceutical companies you know do you want to get involved here we we can we this should be done I can't do this by myself we need to have real trials and real studies of how this will help you know and just was you know their eyes would always cross and never never got any any sort of traction it always went back to sort of disease you know what what disease are you um curing you know what what's the market for it is it a parking disease thing is it an Alzheimer's disease thing and this has been a general problem with Neurology it's very disease Centric it's always sort of and it's always focused on you know how can we develop a treatment for Alzheimer's or traumatic brain injury or stroke as opposed to how can we develop a treatment for working memory dysfunction which is a problem across diseases so the answer to your earlier question is these drugs are very safe they we give them in such low doses to heal the individuals they don't even know they can't even tell the difference between the placebo and the drug really don't even know which one they're on so they're not buzzing thinking like oh this feels good and my working memory is better they have no idea they don't even know their working memory is better until we we show them that their working memory is better so love it yeah so they're truly blind to what's going on um bromocryptine is but one of the dopamine Agonist um can think of a few other um koline like other things like that um do any of these dopamine Agonist um exert this uh impact on working memory or is it um does it vary by drug because different dopamine Agonist uh sort of hit different receptor Pathways and things like that yeah no it's not specifically the drug I mean the the reason for bromocryptine is that it's the oldest and it's the one I was most comfortable with I had to be comfortable with it clinically before I'd give it undergraduates at at pener Berkeley so there's nothing special but other agonists work similarly um there's a there's a drug that's develop a Park which is a compt inhibitor which actually inhibits this this enzyme that we're talking about and that that also will improve uh we'll have the same uh function there's been some future work that Nora and nephrine also seems to be helpful with working memory uh it's not as uh maybe not as um potent as as the dop energic and that that's the point I want to make another another disappointing thing about this whole field of the pharmacology of cognition um you know I I wrote a paper as a resident you know sometimes you're tending to say hey can you write this review paper for us and and I wrote one as a resident called the pharmacology cognition where I looked at all the animal literature on you know uh giving neuromodulators Aline BR um DOP mean or whatever and and there was a lot of there was a lot of animal literature sort of supporting that this would work in humans but was more striking to me was that it wasn't always just a single uh neurotransmitter there were studies where you'd give DOP mean and it wouldn't do anything you give acetal choline it wouldn't do anything but if you gave a low dose of both it would it would be really effective so these you know these trans systems don't act in isolation so we need to also study sort of how the combinations work and that's where another you know where the pharmaceutic companies have the infrastructure to do these kind of say it's very hard to do in a single lab to to do multiple drugs at at at one time you know and then try and look at trying to determine all the different interactions maybe we could talk about a couple of other drugs um that are legal or have and have FDA approval are known to be safe in the right context that um it seems would fit the bill here uh for improving working memory one is um Wellbutrin bronin uh I can never pronounce that um as far as I know it's a uh um epinephrine or norepinephrine Agonist you just mentioned that increasing epinephrine may have a positive impact in working memory and to some extent a dopamine Agonist is there any evidence that um Wellbutrin can improve working memory yeah anything that um boosts norer nephrine can do it the one that we've used that's most used is guanfacine which is actually a blood pressure medication so that's starting to gain some Traction in fact I think there was a study with Co with brain fog for covid showing that improved symptoms with it so there's actually some trials now that are are looking at guanosine and so I would say anything that boosts norepinephrine would be would be helpful um but then again I don't I don't want to leave out the other transmitters serotonin you know increasing serotonin increasing Aline boost other cognitive processes and then you know in a way they can help working memory we talked about working memory being being this Foundation well if if you give veloline and it kind of boosts memory well that can indirectly help your executive function or if you give a a drug that improves your focus then that can indirectly help you know working memory so what I'm really pushing for is is not just a single you know it's going to be one drug you know one drug it's going to be a cocktail and we have to not only figure out what the cocktail is but also figure out who we're giving it to what's T you know link it to the person's own makeup of their own neurochemistry when we get to a point where we'll know we can map out sort of everyone's dop me Norine serotonin levels and then we'll make real progress in in helping them because right now I sort of say with my students what we're doing is just it's just like cutting open the skull and just pouring it onto the brain it's we're not actually doing that we're not actually doing it but it seems that way we're not the Precision is not there yet well you it's great that you developed this um cognitive task that can be a proxy for dopamine levels the cognitive task again being um how many number letter strings somebody can remember um basically working memory performance um there are a lot of tests out there that claim um they can assess dopamine and serotonin a cocoline levels from a blood draw um I've heard of the Dutch test I've never taken it um but a few Mo minutes ago you said that really we one needs to do Patron Mission tomography Imaging which is fairly labor intensive most people don't have access to one of those um it's a clinical tool um so there are behavioral proxies there's neuroimaging but also to my knowledge I I don't know that there's any blood draw that will say hey your serotonin levels are low or your dopamine levels are are moderate your uh Etc there are a lot of companies that market these but are you aware of any clinical or other tools for getting an accurate read of neurotransmitter levels in in a person's brain aside from neuroimaging no and it and it's it's even more complicated than it seems because the Dober ner system is complicated because it's not only just the prefrontal cortex as we talked about it's also the basil ganglia and um so not only do we have to measure dope being just generally levels we have to meure the balance of the dop me in the striatum and the and the prefrontal cortex there's there's a model of dop me um function and its relation ex executive function that has to do with sort of the balance between these two systems that don't mean in the prefrontal cortex is promoting sort of stability it's it's keeping information in mind it's keeping these representations stable whereas the dope mean in the basil ganglia what it's doing is is allowing you to update and refresh you you know the information that you're that you're holding in mind this sort of stability versus flexibility so if you have too much dop in frontal cortex it could lead to a very rigid state where you you don't let anything in and and if you have too much DOP mean the straum and you get too flexible then you can get very distractable so there's a sort of balance of dope mean so it's not just how much dope mean you have in your brain it's it's how much what's the balance of the dope mean so I don't see a blood test as ever giving us that information but I do see there being uh a brain test that that can that can give us this kind of of information of of the two or at least a proxy for it so what I was thinking about when you were talking about asking this question you know for example if you measure pupilary pupil dilation that's a pretty good proxy for NE for the neurogen neric system right so at a given people will wonder what um how to do it we're not going to um go into too much detail here but at a given brightness in the room what we call luminance uh the peup pool tends to be smaller when it's bright and larger when it's um you're in a dim room that's sort of obvious um but at a given luminance the more alert aroused somebody is um arousal as a general term here um not not talking about a particular kind of arousal then the pupil tends to be more dilated it gets bigger the more um norepinephrine is is in the system so if somebody's pupils are really big in bright light that person's got a lot of epinephrine adrenaline right in their system do you use this clinically like when someone comes in are they those big old pupil pup and you're like okay they're probably on a stimulant yeah I mean a lot of what neurology does is is try to look for these windows into the brain and so I think there are a number of Windows into the brain that we're going to be able to develop that can reflect these neuromodulatory systems so that's why I've been so interested in developing biomarkers because really what a neural biomarker is is is trying to uh develop something you can measure easily and simply and cheaply with you know but gives you uh information about how the brain is working so that's a bi you know that's a neurop biomarker working Maring capaity is adult mean biomarker and and we're getting better at that but again we're not putting enough emphasis on it in my opinion to really sort of help you know improve brain health have you ever tried bromocryptine very early on but it's it's such a low do you know the at the dose that the my subjects were getting but like I said it doesn't it's so low you don't feel anything and I should say with even with patients um that take it they they rarely get any side effects sometimes uh with these drugs because this peripheral don't mean they can get a you nausea volume but it's extremely well tolerated you don't get any any anything feeling from it does it change reaction time it does and that's always the question of of how much of this is that we're just sort of speeding up we're just sort of making them faster but for all the the work we've done it's it's pretty convincing that it's it's not just how fast you're doing it you're doing it better uh you might find this entertaining um some years ago uh I learned that athletes uh were taking bromocryptine U pre- Olympics and in the Olympics I think it's a ban substance now um and the athletes that were taking it don't ask me how I know this but I could tell you offline um and I'm not one of these athletes nor was I supplying the Brom crype where using it because uh they were sprinters and it turns out that a lot of the sprint races are won by being first out the blocks there are other factors as well but that reaction time you know hundreds of milliseconds are the difference between Podium and no Podium um and bromocryptine was one of the drugs used it was not on the band substance list uh just a reminder that every Olympics you see there are lots of things being used that are not on the band substance list and I'm not trying to be disparaging I think there's just a lot of interest in augmenting neuromodulation for nervous system function bromocryptine was top of the list at that time I think it's on the band list now um there's a lot of um use of pharmacology now on college campuses and in high school and even in elementary schools and sometimes by parents for their kids to try and improve cognitive function most typically the use of adol viance rlin and other stimulants which are neat ergic dopaminergic Agonist okay so um with the uh discl claimer caveat whatever you want to call it that you know those decisions should always be made with a a trained psychiatrist um monitoring things what are your thoughts about um pharmacology for enhancing cognitive function given that the landscape of society is challenging and people want to perform well they need to be able to focus we've got smartphones distracting us and um to some extent um you know one could say oh well it's cheating to use pharmacology but a cup of coffee is a bit of a noradrenergic Agonist absolutely and um certainly can improves my focus as long as I don't drink too much of it right um yeah what are your thoughts and just yeah I think it you know it kind of gets back to what we talked about there being an optimal you know optimal level of of dop me in your brain I I think if you think about it as just more and more and more is better and that more is better then there's really no there's really no how do you know how much you should be taking there's sort of no that experiment was run in the ' 80s it's called the cocaine uh culture of of Wall Street in the ' 80s that we there movies about it and it doesn't lead to good places right right so so I'm all for optimizing function uh I want to optimize brain health and if you have an underactive you know enzyme that's not that that makes your don't mean levels then I'm all for trying to optimize that along with everything else we need to optimize in the brain so if we could figure out who uh yeah who is sort of on the lower end and boost them up I'm all for that the problem is we don't know if they're on the high end and some of these athletes were actually making themselves worse we know for sure I mean these are healthy pen and Berkeley undergraduates that we made them worse on working memory tests you know increasing by increasing their dope me just a little amount just tip them over just a little little amount and uh and so we we you know without the knowing then it just it seems like it's not well informed to taking it the other thing is I I I if we're going to do this we should do it right I think drugs like Aderall and Rin you know they were developed because they helped patients but they weren't necessarily developed with knowing how exactly they worked I mean that's how the pharmaceutical company work too yeah I mean just it works so let's do it I'm all for that as a physician um but if I had my choice uh you know drugs that boost up multiple all the catac colomines the ones that boost up dopamine epinephrine and norrine I I would steer away from those because you have no control over how you're modulating the system uh again I was sort of talking about a cocktail it's it may be a little bit of dope mean and a little more norrine but if you give take something like riddle and adol you're just getting the same amount so it's it's kind of if I was to start to sort of experiment uh then i' i' i' se you I wouldn't use Aderall aralin as the as the drug that I think would helpful even though they're clinically sort of useful I use things like bromocryptine and guanosine where they can modulate a very specific drug and then and then yeah then the goal is to to optimize and and that's what we're trying to do with cognitive theer therapy and everything sleeping better and better nutrition all these are aiming to optimize not you know reach some super human uh potential right just bring out the best in in people's abilities right um and I'm I'm so glad you mentioned sleep um I would say you know sleep is the the Bedrock it's the foundation of mental health physical health and performance I mean without that pharmacology might Bridge you for an afternoon but you're going to pay the piper somehow um our friend and colleague Matt Walker obviously has uh been beating that drum for a while um what about drugs like modafanil which are thought to be true cognitive enhancers um as opposed to um drugs that just kind of are designed to ramp up levels of alertness as many of the drugs we're discussing do yeah it's hard to know I mean I think certain um drugs just improve General abilities either they speed how fast you can process it or how efficient you can process or or narrow the focus of your attention and that just helps all abilities so it's so so it's hard to say I think just just has to be more work on really understanding what specifically uh you know these drugs are doing that's why BR crypting the doener story has been so interesting because it's a very specific effect with a very specific mechanism I like to see that be done with with other neurom modulators maybe we could talk a bit about some of the disease conditions that you treat and the role of working memory and dopamine in those conditions as well as other transmitter systems you know one subject that we haven't talked about on this podcast uh previously but is of tremendous interest to people is traumatic brain injury or concussion even mild concussion and um before we we recording today we were talking about football but just want to remind people that football is just one instance of an opportunity to get a concussion or traumatic brain injury most traumatic brain injury and concussion is not due to football it just gets a lot of the attention but you've got bicycle accidents car accidents playground accidents um uh maybe you could list off a few more um but how common is TBI and concussion and and maybe you could just perhaps list out some the other situations where you see a lot of this um that it's a bit more cryptic that people wouldn't necessarily think that sport or that that population gets TBI but they do yeah I think concussion uh is much more prevalent than we we realize and and the numbers have gone up and up not because it's becoming more common just it's becoming more recognized and I think uh you know we we underestimated and trivialized sort of what a concussion is you know is is that it's just a you know something that is um you know just you're going to recover from it I mean still the old school Thinking by a lot of neurologists is that everyone gets better within a couple of months you know just just wait it out and you'll get better that's just the normal time course of concussion but as we've studied it more uh we realized that there's actually quite a large percentage of people who a year out they're still suffering problems they still feel like they're not mentally clear and they still are sensitive to light and they still feel a little dizzy and and just the symptom you know there a host of symptoms that just one year later after a concussion where they didn't even lose Consciousness you know that something that they may not have even talked to their doctor about is is uh is is lingering um and so it's a real this we call this persistent postconcussion syndrome and that's the most worrisome to me because it is true that most concussions will recover luckily the brain is incredibly resilient incredibly plastic and it will heal itself um but there are a lot of patients where just it just persists and those are the most worrisome to me because we don't have very good interventions to try and help that and I don't think we take these patients very seriously when they're complaining of something that seems very vague and not very specific to most most doctors what do you tell a patient who comes in and has clearly had a concussion um mild or severe concussion you know maybe car accident maybe a sports injury maybe they were knocked out cold maybe not but they're having some headaches some photophobia you know sensitivity light just feeling not right I I've had a couple of these um unfortunately and you just feel off you don't feel quite right um and some of that manifests as Focus issues this was some years ago I like to think I'm through it I've had scans and I'm good um thank thank goodness um but what do you tell them besides don't get another one yeah well first of all I I explain what concussion is what I found in neurology a lot of What patients want to know is just they just want to understand their problem not walking in expecting a cure just just understanding what it is having someone understand what what happened to them is is very helpful and comforting so what we mean by concussion and we in the clinical world we use M traumatic brain injury kind of synonymously with concussion uh it it's it basically is is a tearing of axons it's the bra the brain cells have these long fibers that communicate with each other and they're called axons and when the brain violently moves forward and backwards if you're in a car accident and you have your seat Bel on and you suddenly hit you go from 50 to zero your head violently goes forward and violently goes backwards and that angular Force actually tears and stretches axons in the brain so if you've had a concussion you have torn some axons I mean luckily we have billions of them and so if you tear a couple of thousand you you will Rec you will recover but you you have torn axons it's a real neurological it's a real brain uh injury even if if even if you haven't lost uh Consciousness and you've only had symptoms for a couple of days um but there and there's a correlation the longer you've lost Consciousness and the longer your symptoms last the more axons you've you've torn there's kind of a direct relationship between the two so the so the mechanism is is these torn ACC so now nurses don't communicate with each other and and you know that the brain different brain regions are not communicating with each other um so and it turns out the most common place for axon SATs in the in the frontal loes and so now we talked about all these things that the frontal loes do to orchestrate the rest of the brain while it doesn't it has some injured Pathways and that's why a lot of the symptoms that patients have are these kind of mild executive symptoms this this mental fogus that they're describing is this ability just this unability to to to get things get things done they don't lose knowledge of who they they don't forget their name or you know forget where they live or lose memories from the past or anything like that but they just they don't officially get things done as well as they used to it only takes a little bit of a drop right you people think you have to have a big uh drop in performance to have it have a real life impact just a 1% drop and you're you're having a hard time doing your podcast or teaching a lecture or whatever you might do a 1% drop sounds like a um a frighteningly small change um required to to negatively impact life so um how about a poor night's sleep I mean what kind of drop in prefrontal cortical function are we looking at um from a let's say I normally get seven or eight hours or six to eight hours and I suddenly only get three or four are we talking a significant detriment I I do think so I I do think that yeah that that that the it is significant this a poor night's sleep and and and we all know we all notice that I mean it's very it's very obvious I mean um and you and and you know it's hard to sort of quantify I'm a baseball fan so I can quantify it like if you think about it in a pitchure and how fast they throw you know a small drop for them someone who's throwing 100 miles an hour just a small drop turns them you know from really Elite to someone mediocre maybe it's more of a 10% drop but but but it's still relatively small drop can have a a huge impact I think people think that just because you're a little bit off that's not going to that's not a big deal you kind of you kind of work through it and that's what most doctors say you just just just plow through it just just work your way through it you're going to get better and um as opposed to saying yeah you really had a brain injury um this is what happened we need to rehabilitate you just like we would do if you tore your anterior crucial ligament I don't know why teing your crucial ligament or your kiles tending gets more interest than than tearing axons in in your brain it's it's it's amazing to me that that there's more emphasis on Orthopedic injuries than than brain injuries yeah I don't know why that is either I think the brain is mysterious enough that um most people and and um many clinicians just kind of back away with hands raised but if you are in the field of Neurology or Psychiatry I suppose that then one has officially signed on to try and resolve these matters um so for somebody that um has a traumatic brain injury or or low-level con concussion excuse me um would part of the uh primary advice be to try and get one's sleep as as good as possible given that sleep deprivation can compound um traumatic brain injury uh induce deficits in working memory and who knows maybe a good portion of the deficits in working memory due to um traumatic brain injury and concussion is because of the sleep deprivation that it can cause so it get it can get circular know not only that but one of the most common symptoms that patients my patient with C have is is their sleep is disruptive they they they're and that's true in neurology it's fascinating almost every neurological disorder my patients complain their sleep and and I started asking you know not a lot of neurologists ask you how your sleep you know but I real I remember back from my residency one of the first things my attending would do when we got to the ward is said I just sleep last night and it just across the board you know patients are not falling asleep they're not staying asleep and it's it's uh we still don't understand why just brain injury does that so almost every concussion patient says I'm not sleeping well which then compounds you know compounds the problem so optimizing sleep obviously optimizing nutrition um there's a a question about activity it used to be that uh we used to recommend you know you had a concussion you should you should s don't go to work you know sleep you know just just take it easy for a while don't exercise keep the BL blind strong but now it's it's it's the idea is that you should really get up and moving as best you got to you got to do what you can tolerate you don't want to give yourself a you you don't want to give yourself more of a headache or more light sensitivity but as much as you can tolerate is is the the thought these days about sort of promoting recovery and then really getting your brain back working I think you know a lot of my patients they're off from work for a couple weeks and they they feel fine and they they think they're pretty much normal and the first day of work is a complete disaster because until you actually test it in real life you don't know how what kind of troubles you have so I don't recommend going back full steam but I do recommend going back trying to build up these these Stills skills again and then I think we you I think we need to develop therapies that people will will use um you know things like goal Management training which involves a therapist and you know health insurance doesn't pay for this so 99% of my my patients don't get any help you know by any kind of intervention uh unfortunately but now we talked about technology things like um brain HQ do you know about brain HQ so Mike merenik um which I know you've talked about with with Eddie um developed a a a company called posit science where where developed these brain training games that that can help improve specific cognitive functions and they're very easy to do because they're online and they you know they're there's science behind them and and you can you can do them so that in that way you don't have a therapist in your room but you can online sort of do these sort of things that are targeting specific Mech mechanisms to trying to improve the kind of things that we think are impaired by concussion and I'd like to see more patients get started on some of those things unfortunately if you go on the web and just say I won do brain training you'll be overwhelmed with things and you don't know what works and what doesn't work I I think the work that merenik and colleagues have done we'll provide a link to that I don't have any Financial stake in his in his work or products um trainings that is um but I will say I think Mike's work has been um tremendous I mean he is so far ahead of the curve 20 years ago everyone was talking about neuroplasticity in critical periods um they gave a Nobel Prize to it to my scientific great-grandparents David hubel and Toren and weasel um and they deserved that Nobel Prize but there was a kind of a central tenant of neuroscience at that time was that critical period plasticity ends around adolescence or one's early 20s and that is simply not true and merenik really I think one of the people who deserves credit for um making it clear that plasticity is ongoing it takes some focus and and work to access it in adulthood but that we can all access neuroplasticity but it it takes it's there so I don't know they should give merenik and Nobel too but you know I'm not on the committee so um just a little editorial there the description of specific cognitive trainings that can improve working memory in people that have had traumatic brain injury or concussion as well as our earlier discussion about the development of frontal Lo function and plasticity of frontal L function makes me wonder is the working memory circuitry and frontal loob function a use it or lose it kind of circuit meaning if somebody you know goes to high school graduates high school and then gets into a lifestyle or college and then graduates College as well and then gets into a lifestyle where they're not reading very many books they're definitely scrolling social media they're carrying out their daily tasks with you know apparently uh High degree of functionality um but they're not really pushing these forbrain circuits do we imagine that some of those forbrain circuits regress um AKA use it or lose it um seems to me that a few years back maybe 10 15 years back there was a lot of interest in you know how to maintain cognitive function in fact one of the most common questions I would get even as a neuroscientist primarily focused on the visual and autonomic nervous system was how do I keep my memory as I age it seems to me that training it up and then continuing to use those circuits is would be a really good way reading books without forcing oneself to finish the chapter even though distractions jump into one's head things like that um for me it's when I go to the gym I not to bring my phone and if I do I'll listen to one album of music but I won't allow myself to play on my phone I try I mean not interrupting a conversation with text messaging I mean basically the the landscape I'm trying to uh draw here is seems like the world is designed to to disrupt that the modern world is designed to disrupt working memory and cognition of the frontal loes right right and we need to do some real training just like muscles and atrophy and cardiac Fitness atrophies if we're not doing ready uh you know resistance and cardiovascular training is that set yeah I think that's fair I think you know of all the systems uh that decline with aging not every brain system declines but certainly the frontal executive system we're talking about is one that takes more of a decline than others that's just how it is with with healthy aging um not surprising it's it's the most complicated system and it's probably the most biologically costly and so you know the more complicated system is going to uh take more of a hit than than other systems and so certainly um I don't know about regressing but certainly we're not we maybe accelerating this this this uh decline that we know exist and but a way I would think about it though is is that not just um trying to prevent the decline but what we talked about before there's no reason not to optimize I mean if if everything is couched and I don't want to get dementia and don't want to get Alzheimer's disease and I don't want to get this and that I think that's not the way we should be looking about it we want to look about op optimizing health and and uh brain health and and and getting up to our optimal levels um because otherwise we're always playing defense instead of playing playing offense and that's really hard for neurologists we we have a hard time thinking about brain health even though we're the brain Specialists we think about brain disease and we're just now as a field start thinking about preventative neurology which seems and and thinking about it not just like stopping Alzheimer's disease but uh promoting healthy Health in a healthy brain just you know neurologists don't talk to patients about or healthy patients about being healthier I love how candid you are about the medical profession um and I like to think it's changing I don't know something happened in the in the 2020 2021 um era I I feel is just my my bias but I feel that the general public started becoming more aware of the things they might do to support their mental and physical health maybe they had more more time on their hands but I think there was just more foraging for information um I love the idea that through simple practices like forcing oneself to read a book chapter start to finish without looking at one's phone um even if it takes twice as long as one would like um redirecting one's focus when what Focus moves away is it's a way of keeping working memory and cognitive function online maybe even strengthening it as you said optimizing it um you know I think that there so much emphasis now on physical health which I think is great sleep thanks to Matt Walker you know you really you know brought that torch in on sleep um and now others like myself are are really you know trying to amplify the message of the critical role of sleep but also you know most people realize they should probably at least walk um as you know the 10,000 steps thing is not a bad idea um getting some heart rate up a few times a week or more maybe doing some resistance training a few times a week or more and then and not just for athletes but for elderly folks men and women you know um I feel like we need the same for cognition for me for uh brain function and there just isn't a structure to that no one can say right now you know you need to do uh three chapters of reading you know fiction per week or uh you got to read a you got to learn a few new vocabulary words and then write sentences with them they do it in school but then we're just you know set into the general population and right and most people I think regress right yeah I mean I I think the big problem uh with brain health is is trying to have a measure of what brain health is and it's interesting to me again as a physician um thinking about it from a neurologist standpoint um when you go to your family doctor your primary care physician every year from your yearly physical uh they examine every organ in your body except your brain your lung your heart you know your skull system your skin but what what do they do for you you know outside of having a conversation with you no cognitive task there's nothing no working memory task they don't measure your your brain at all and it's not their fault there we haven't provideed the field do not provided them with a test of of of brain health right and so part of the problem is we don't have a measurement of brain health I'm involved and something called the brain health project which is at UT Dallas um which is their goal is a study to enroll 100,000 people in uh and they've been developing a brain health index and that's a complicated thing to do but I I really believe they're on to something because it's not just cognition it's cognition it's it's social it's it's lifestyle like sleep and and it's it's um well-being you the brain a brain health index is going to cover all of these aspects so they've developed quite a interesting uh important index which which can um which does try to capture all aspects of brain health and then can be used to track uh where you can track your brain health over time with interventions that they've they've developed so we we need something like we need to First once we develop a brain health index that's that then then we have something to to follow and to and to be able to measure if if if we are optimizing our brain health otherwise how do you know if you're you're optimizing your your brain health you don't your doctor's not telling you you don't know um all these games you get on in the web don't really tell you um so when we develop that uh then all of the things that can promote brain health will be measurable and I think it will take off the way physical fitness did perhaps you get enough of it from your work but given what you know about brain health and approaches to brain health what are some of the things that you do besides sleep exercise nutrition um in terms of um trying to optimize brain function I mean do you make it a point to read fiction do you make it a point to learn new new skills like instruments things like that again maybe your profession and your and your personal life keeps you busy enough that you don't have to do those things I mean for me I uh Gathering organizing and disseminating the information for the podcast feels like the the the the heavy lifting mental work for me but but I'm keenly aware of the fact that we're I to read more fiction or um learn an instrument uh I mean everyone else around me would suffer if I learned an instrument but um that it would probably benefit me in some real way what are the things that you do or and that you um you think are kind of access points that hopefully people also enjoy yeah no I I I agree with that I I think when you have a a busy career and you're doing many different things like teaching and research and seeing patience I've always felt that I I'm maxing out on on on full my executive function is being tested to the Limit but you're like an ath you're like a professional athlete of the mind yeah in a way way but then then you realize there's that that's that's not you know that's not everything there there's so many other aspects uh everything emanates from the brain so you start to think about what should I be doing in my my life as as a a father and a husband what what what should I be doing you know in terms of promoting social interactions with friends and and uh what should I be doing for sleep and health uh sleep and nutrition um and it's fun you bring up books I I think you know I went probably 20 years where I never read any non you know any fictional book and said this this can't be good for for my brain and then just consciously started you know reading uh reading um books and reading his and more non-fiction books and just listening to books or reading I still like to read the hard hard covers you know likewise unfortunately when I was a undergraduate you know with Premed they don't let you take any courses that are interesting so I never learned any history or or you know all the books that I never read I started reading my kids you know English literature books that I never got a chance to and started reading history and so yeah I always felt just like just increasing you know just knowledge was was another you know like I said our brain just stores information that's one of its his jobs so that that's got to be useful but but again um all of these things that I do believe help brain health we need we need some way to me measure it I think um certainly if you feel healthy that's an important thing if you feel like you're healthy physically or mentally that's that's good that's a good start but if we actually have a way to sort of track it the way we can track you know heart disease and lung disease and skin and things like that I think that would really boost everyone's confidence that this is really making a making a difference on the basis of today's conversation I'm going to read some fiction uh I read a lot of non-fiction um and I enjoy it I listen to some Audi books but I I just it's crazy to me because I'm a neuroscientist by training and I understand neuroplasticity and I do know a bit about Fitness and the key role of remaining active kind of use it or lose it and maybe improve it right kind of that wasn't intended to rhyme folks um kind of behaviors but clearly based on everything you've told us that if we don't exercise these working memory and other Co circuits for cognition like why should they stick around and I and I'm beginning to think that social media as entertaining as it is and I I learn there and I teach there but that it's not a cohesive um plot right it's like those baby otters that really cool looking dog that I'd love to own I'm thinking about getting another dog um this interesting conference you know it's it's like random pseudo random tailored to me of course because that's what their algorithms do but but that's not following a plot character development um antagonist protagonist um uh any of the the like things that provide like cognitive richness um it's kind of obvious as I as I say this but I feel like we're divorced from these things that really helped evolve culture and evolved individuals and and it takes some discipline but like a run or going to the gym you do it a few times for shorter amount of time with less intensity and pretty soon you're up to speed and there's an upper threshold unless you're going to be a pro I'm not I'm certainly not going to be an English Lit you know Professor you know so I don't think uh obviously boosting executive function is incredibly important but I don't think it's going to happen just with technology I think it's going to need it needs human interaction I mean I I believe executive fun should be taught in you know school as one of the cour you know as as a course um uh this school management theor that I talk about could be taught in school it's what you do with your students for example when you have a graduate student um and they have to learn how to read the literature and design experiment and Carry Out The Experiment uh there's no techn ology that's going to just be able to teach them how to do that you've got to intervene sometimes and say stop reading all those papers they're not relevant okay or you know you're you you piloted this enough get going it's it's that kind of wisdom that that that you get when you get older that that that that allows that has to be uh has to be on top of the the technology so that's why I think um we also need to it needs to be directed so whether it's in school or whether it's in a patient I think there's still needs to be someone coaching us you know and I know that's why life coaches have have been some people really benefited from life coaches because someone just it sounds obvious when you tell your kids you know just write you know just just do it this way you know break it up into little pieces it seems so obvious but to them it's not always obvious and they just need to be told something simple for it to make a big difference and in school we were we were brought along step by step and there was context so why wouldn't it be the same in adulthood um I'm realizing I should probably learn how to play chess yeah seems like a good game right CH chess yeah any any one of the working memory you got to keep information online there there's a bunch else there um I think uh but as a tool to improve cognition um I was also thinking you know some people Orient more towards the Arts my sister is really great about um she's a therapist in San Francisco but also um takes like theater classes and she said you know like improv is like forces you to like keep on your toes keep the context there you're up on your feet like you know and I I wasn't a theater kid I did the crew I did like the pulling the curtains and stuff till I went and did other things but but but that whole Biz is about um being you know learning the novel rule set in the moment you know it's improv by definition absolutely I mean anything that requires you to have that you know where there's a goal and you've got to break it down to sub goals and you've got to do it simultaneously and you got to filter out the extractions and you know you know for example my my kids got me one of these pizza ovens for for uh Christmas and you know how you you think it's easy you just sort of make some pizza and throw it in the oven and done that's we're I'm on my third time and it's still not even round I'll come over and test that sounds good that sounds good um and and you're in a city with great food so the standard is really high um tempted to make a reference to the cheeseboard pizza but I want to keep the lines as short as possible cuz they're already too long um maybe we could talk a little bit about some other unfortunately common disease States um Parkinson's and Alzheimer's let's start with Alzheimer's I think um few few things um uh scare people more than the idea of getting Alzheimer's especially if they have Alzheimer's in their family first of all what is the genetic link with Alzheimer's if one has a parent or grandparent that got Alzheimer's is there a known um increase in in their one's risk for getting Alzheimer's it's not that straightforward as other diseases there's diseases like hunting's disease where it's a very strong link that if you have uh a parent you have a very high chance of getting it but there's so many factors that uh it's not necessarily case that you're you're increased your risk of getting it there are families where there is something special about the family where it just runs in families but uh I try to to um not scare my P patients children into worrying that that they're necessarily going to get Alzheimer's because it's not that straightforward as I understand Alzheimer's is a a nerd gener disorder um impacts the hippocampus among other structures there's been some debate in recent years as to whether or not the whole amalo hypothesis is real or not there's a bunch of unfortunately false data accusations and that whole thing but my understanding is that if you look at us slice of human brain from an alz a patient that died with Alzheimer's maybe even from Alzheimer that you see plaques and Tangles you see these um subcellar structures and buildup and that our basic understanding of Alzheimer's that's in the textbook and that most people have heard of um is still correct right yes okay because I think a couple years ago it was you know unfortunately the way social media sometimes can work is that you know the idea was that it was was all wrong you know all wrong and indeed somebody somebody fudged data they made up data and that's terrible um but Alzheimer's is a neurogenerative disorder includes the hippocampus plaqu and Tangles are present in the neurons those are not good for neurons as I understand so what's the controversy like and and why don't we have a treatment for Alzheimer's yet I feel like almost every other psychiatric disease including Parkinson like there there are certain things you can do to at least push the system in the right way why is Alzheimer's and other dementia is so tricky yeah I mean it's very frustrating because the neur degenerator it's just it's so uh so many factors that are probably involved in the path pathology that there's not one you know one single um transmitter the Parkinson's disease it's a decreased doope mean and so one transmitter can make a very big difference um early on an Alzheimers it was discovered that there was low AEL choline in in the brains and the only approved uh treatment for Alzheimer's disease is a drug that boosts Asal Coline what's the drug right it's called deasil there there's a few of them they're anticolon estras Inhibitors that boost Asal choline they've been around for 20 years or more and you know the reality is when you give it to your patients they don't see much of of a difference because it's it's not the primary deficit so the real problem has been trying to find out what is the primary mechanism that's leading to this the the wide range of cognitive behavioral issues and and and there doesn't seem to be at least one neurotransmitter that can make the difference and so now the push has been is there one is there something else that we can do can we can we block amalo can we block something in the pathology and again it just has not been successful it it's very frustrating because I think it was over probably 35 years ago I saw my first Alzheimer's patients and I don't believe I save that much different to them now you know except that we have a lot more things we can do just on the social side of things but unfortunately for drugs we don't have anything that's been really transformative um but again that that's I I think part of a and being an neurologist it sounds very depressing but I think part of the F what the family isn't always looking for a cure of course that's they'd like to have a cure but I think them understanding what's going on what to expect how to handle the behaviors is what they're really after at least until we find you know a cure Parkinson's you mentioned is a deficit in dopaminergic function do largely to uh degeneration of dopaminergic neurons there there's some some effective treatments right lopa um did you know there's this over-the-counter stuff that's sold that a lot of people take who don't have Parkinson's I'm not suggesting they take it um called Muna purines it's the velvety Bean yeah I've heard of it it's 99% elopa over yeah it's in present in like some energy drinks and supplements I people can go buy it I'm not suggesting they do that I actually tried it um boy feel being really dopamin out does not to me doesn't feel that good yeah I felt kind of agitated my vision got a little you know twinkly it did not feel like a high of any kind and then I felt lousy for a couple hours after it wore off yeah I don't think you can really get in enough elopa to get enough into your brain that that happened early in neurology when it was discovered we couldn't give our patients enough elopa without them feeling bad because it's also um metabolized in the peripheral and so it wasn't until we cinet came along which is has this debox decarbox inhib that blocks sort of the the the breakdown of doine that we were able to sort of get enough dopamine into the brain so I'm not sure yeah so that's why I think um it's not going to probably get the levels up high enough in in the brain so Parkin's patients are given lopa um or bromocryptine or drugs like that going back to alzheimer's for a moment I mean what do you tell it somebody who has early stage of Alzheimer's you just say listen try and get good sleep try and keep people around you stay cognitively engaged try and keep those circuits going through behavioral induced neuroplasticity but we're just going to watch the the the um steepness of the decline is that really is that really all we've got all we've got is to yeah is to help them uh with everything that comes up on a day-to-day basis a a lot of the problems um the memory problems tend to be something that uh families can help compensate for but but you do get to a point where you can't be with someone for 247 it's it's a real burnout for for caregivers a lot of the behaviors that come up uh patients get kind of delusions and agitated and and some of the uh medications that we use for uh other conditions uh are helpful for for treating that but it's really just a purely symptomatic therapy and the more socialization that patients get the tend they tend to do better there was a study back at pen way back that if you showed patients um family movies or family albums it was a real it was better than any drug you could give them to sort of help their behavior so there's still those memories are in there and they were making some type of contact that was was helping them emotionally that you couldn't turn off with with a drug so I think the more we do things like that the the more we'll be helpful for them at least in a you know symptomatically you I've seen a number of videos and on social media people with Alzheimer's who listen to a piece of music or people with Parkinson's that hear a piece of music and that seems to uh resurrect some at least emot context appropriate emotional state where he kind of brings the person to the to the surface um again um yeah it's a kind of a tragic situation for Alzheimer's right now it seems like if ever there was a call to arms for the neurology community and um biotech and behavioral Tech would be for for for Alzheimer's for the treatment of Alzheimer's yeah absolutely I will never ask a guest to um comment on the the the good or bad behaviors of other people except my own um but uh there's a Nobel prize winning neuroscientist and I visited him um he's at a big East Coast School uh back in 2010 and during the course of our one-hour meeting he consumed no fewer than four pieces of Nicorette gum and I said I got to ask what's this about by the way he's extremely sharp still um and he said oh yeah yeah yeah you know I used to be a smoker but smoking is really bad for you because you can get lung cancer dipping is bad for you because you can get mouth cancer but nicotine these are his words by the way is protective against Parkinson's and Alzheimer's and it keeps my brain sharp so I chew Nicorette all day long and I thought okay well he's not he is an MD actually um and I thought that's interesting and I did an episode of this podcast on nicotine it by the way can raise blood pressure it's certainly smoking vaping dipping or snuffing not good bad don't do it but there is some interest in the use of nicotine as a cognitive enhancer so I'd love to know your thoughts on that um and I'd love to know your thoughts on his statement about nicotine being um a potential way to Stave off Parkinson's and Alzheimer's with the caveat that he just kind of threw that out there and this guy's sort of known for just kind of throwing stuff out there every once in a while I have a feeling you know who this person is but um in any event what gives yeah well I don't know anything about nicotine staving off any neurogenerative disorder um but nicotine was used uh and was used in a number of early Alzheimer's studies just because of its effect on Co the coleric uh system so there is some truth to that uh the col energic system is is imp you know dysfunctional and Alzheimer's disease and and boosting the colon energic system probably is beneficial I mean patients that we give the Anolon necessories Inhibitors there are some families that say yeah he just he's he's remembering more and he's just doing better so they're there I've seen positive um things to it uh it doesn't really slow the course of the disease that's the problem the disease just carries on even though we're symptomatically improving the symptoms but again I think it's going to take both asine and something else I think we don't know should we give dopamine with the with the nicotine or the esal Coline or should we Nan nephrine I think it's going to be a cocktail which which again pharmaceutical companies you know have not tried a cocktail of neuromodulators for Alzheimer disee they've just tried Aline sounds like you should be running the FDA no disrespect to the current um people in charge by the way but maybe actually I'm I'm a um big believer that there shouldn't be individuals in charge of large organizations there should be panels I mean there's so much talk about diversity but they appoint individuals you can't get it right anytime there's when there's only one person by definition so right committees folks committees um anyway another editorial are there any sex differences male female differences in um sort of uh these dopamine levels working memory um injuries concussion like things that would Direct people toward different routes of treatment um given that you know maybe there's more susceptibility in one case maybe less susceptibility maybe certain neurotransmitters are more effective in um improving symptoms in in men versus women do you see that in the clinic yeah that's a great question um there was Emily Jacobs who's a professor at UC Santa Barbara now in the psychology department when she was a graduate student in my lab studied the role of estrogen on working and Dober nergic function and what she brought to my attention at the time and it was embarrassing that I didn't know was that there's the frontal loes are full of estrogen receptors there's probably more estrogen receptors in the fontal loes than any other part of the brain in men and women estrogen boost is dop me so you higher estrogen levels correlates with with increased dop me uh levels and and there were some anecdotal evidence that in post manop pasal woman women who were put on estrogen that they're working memory improved and there was a kind of evolving link between estrogen and frontal low function and she did this amazing study where she studied healthy uh Berkeley undergraduates at two points in time during the mental cycle when EST was at his lowest and what was his highest and she also um gentite them for this enzyme they we were talking about to know if they were sort of lower or higher on the dopamine level and then put them in the scanner and measured frontal function and and showed that there was a clear frontal low function was modulated by where they were in their estrogen cycle when they were low estrogen they were low dopamine and if they were low estrogen and low dopamine to start they were really had decreased frontal low function and decreased working memory ability so it it fluctuated uh based on this interaction between estrogen and dopamine suggesting that you know not only is dopamine is important but hormones are are clearly important and they they work synergistically so you know as we're develop in this this cocktail um we certainly have to bring hormones into the equation and learn more about it there's just so little information about um hormones and cognition yeah one of the themes that's come out of some of the episodes we've done with MDS who specialize in endocrine health is that for both men and for women um optimizing estrogen levels is really important for cognition and vascular function I think people mistakenly here okay testosterone men you know estrogen women obviously both hormones are present in men and women in fact I think um I know that testosterone levels in women are actually higher than their estrogen levels when you look when you sort of um uh use the same units of measure uh it just so happens that they still have lower testosterone on average than the typical male but that men whose estrogen levels are too low suffer cognitive defects and Vascular defects so this idea that more testosterone lower estrogen in men is is the is the ideal right and um uh it just doesn't hold it doesn't hold I mean unless you want to be dumb and have a heart attack it just doesn't it just doesn't hold um very interesting do we know what estrogen's doing there is it it's it's specifically raising dopamine um we don't have to get into the synaptic biology but so interesting yeah it's actually boosting dopamine activity so it's making more dopamine available yeah yeah it's it's really um amazing and and um and to think about it sort of fluctuating um certainly during the menal cycle we can think about how much it fluctuates an IND woman over 30 days but then you can think across individuals you can think about how how much it can account for individual differences so not only sort of knowing your dop me level but just knowing svest and uh C is really going to be important interesting is there any evidence that physical exercise can improve working memory and cognition separate from the known improvements in cardiovascular function and blood flow to the brain that occur with exercise like is there anything about going for you know a 45 minute bout of exercise you know pick your favorite exercise and then doing cognitive work immediately afterward when presumably the catacol mees dopamine or epinephrine and nephrine are going to be circulating at least in the blood at higher levels is is there has that stuff ever been explored in all of the groups around the country that are trying to develop cognitive therapies they they often use aerobic exercise as as as another type of therapy and and so for example the group at University Illinois uh champagne AR Kramer group has done aerobic exercise quite a bit and they can find it just as effective as cognitive therapy and improving executive function just straight up wow aerobic exercise wow and um and so you know the hard part in the real world is is how do you get you know a seven eighty old you know to do the kind of aerobics but but now with you know recumbent bicycles and now there has been studies with 7 year olds with just putting them in mostly with overcoming bicycles is sort of Designing we have to think about ways to design exercise that can get aerobics up but it's it's uh and you know neurologists are start I think you know my field is starting to realize that there's there's we got to tackle this at all all every way we can and so now I'm hearing you know you hear more neurologists talk about that you know 30 years ago no no neurologist would say you got to exercise more you know or just now it's sort talking about exercise and nutrition and sleep and and uh you know it's all becoming sort of part of our package of how we're going to help our patients but the arobic exercise is is super is super interesting and and I think it's going to be you know that that kind of made me think that um what we didn't talk about was mindfulness and so when we add a lot of these studies also if they add mindfulness train training to the hardcore goal Management training it's it's better than than just the the the executive training alone just learning skills to stop relax refocus kind of gives this sort of boost uh to Executive function as well yeah I think of mindfulness likea sort of well there's no such thing as traditional meditation I have to be careful here but but the the sort of stereotypical meditation of closing one eyes closing one's eyes excuse me sitting down lying down and and just focusing on one's breath and then redirecting one's Focus to maybe Third Eye Center you know area between the forehead just redirecting Focus redirecting I think of meditation of that sort as a focus exercise right it's it's not so much a perceptual exercise because thoughts are kind of you know doing what they're doing um it's like Focus exercise and that's half of the problem with not achieving our goals right is we we lose our focus and so building into sort of strategies to to main focus Focus uh you know to stop and relax and refocus is is an important strategy for boosting executive function so and that uh and it doesn't seem to matter what you know I know there's all different flavors of mindfulness so we just happen to use one when we were studying it it doesn't yet I don't think we know enough about how we should tellor the mindfulness but most forms of mindfulness will work of of the type you're talking about that's similar what I described as similar to what you just explored exactly I mean amazing to me you know 20 years ago if somebody wanted to talk about neuroscience and mindfulness yeah on a major University campus let's say Stanford or uh Berkeley was probably a little bit more tolerant of these ideas at that time just given the the kind of culture um they wouldn't have been laughed out of the room but but there was a lot of skepticism and I feel like now mindfulness meditation breath work the idea that oh my goodness breathing can impact your emotional state yeah I mean that should have been obvious but now that people are on then now of course there's a lot of interest in psychedelics that's kind of a new emerging therapy carrying more risk potential risk but it looks like it's very likely that some of those are going to make it through the the FDA filters at some point but the conversation we're having now you know neurologist and neurobiologist talking about mindfulness nutrition we're talking freely about nicotine you know we're not suggesting people do that bromocryptine as it to optimize cognitive function I mean this conversation would have never happened um seven years ago no it's just the field has changed yeah neur I he neurologist talk about it all the time do so do you try mindfulness and if you do does it make your day do you feel like you perform better that day yeah thanks for asking there two forms of yes the short answer is yes um I there's a very specific practice that I've used since 2017 that's really benefited me so much which is um I call it non-sleep deep rest but it's based on a practice called yoga Nidra where you just liee down and it's uh these are free audio scripts online we can provide links to these um and you go through a body scan and you do some long exhale breathing which emphasizes the parasympathetic AK relaxing aspect of the autonomic nervous system I know you know this I'm saying that for the audience um and it does involve some intentions and things like that but it can also just be um self-directed relaxation and I emerg from that with much more mental and physical Vigor than I did prior and this only takes maybe 10 minutes there's also a 30 minute script I do those and then I do uh mindfulness meditation the thing about mindfulness meditation that the biggest impact for me has been the problems of My Life um get re um I get a different perspective I start thinking about things in different domains of time like this thing that is like a problem that I've been dealing with for instance um I start to think you know like in the course of my lifetime this is you know a relatively small not small thing but in relatively small time bin and I sort of think about you know best course of action given its real role in my life and what I want Etc so I feel like it sort of orients me in time um so that's been a major effect for Focus the best tool I know is to you know put the phone in another room right that's kind of a don't um and I know our friend Eddie Chang neurosurgeon chair of neurosurgery at UCSF he's big on on mindfulness meditation do so do you meditate no I think that's one of the things we're talking about what should we do besides reading fiction I think that's that should be on my list because because I no because it's just amazing that I that the patients tell me about it and what we've seen from our our studies um you know a lot of this like again I was saying before is is if we had some measure of uh you know brain health that we could see the impact of it would sort of push us towards towards you know probably doing it more I think another thing that we didn't sort of talk we talked a little about with dopamine is are there other kind of brain states that sort of uh you know predict you know you know how you're going to respond to these therapies and and how if if you're going to benefit from them and and uh you know we've we've done a lot of work with sort of measuring sort of the large scale organization of the brain and brain networks and that's sort of very popular idea in in Neuroscience today sort of moving away from sort of what is this we've talked a lot about what the prontal loes do but the frontal loes are part of these networks in the brain and and um really sort of your this state of your networks is really important factor as well in in addition to sort of your your do you sort of neurom module you sort of neurochemical profile yeah tell me more about this I mean um you actually uh preempted my next question which was going to be and this is my favorite question to ask Carl diero taught me to ask this way back when like what are you most excited about now because I know the work you've published and and we and you've done a magnificent job of of sharing the details of that and and work of others um in a really informative and in some cases actionable way but what are you what are you really excited about like like if if there were no Financial barriers to your grants Etc you had a thousand people working what what what's the what's the thing that's hitting your dopamine circuits these days yeah well in the grand scale I'm excited that things that we've learned over the last 30 years not just in my lab or your lab or anyone's lab is actually now being translated to actually helping people I mean when people ask me what I do I say I'm a neurologist because that's at my core what I feel I am and I feel I got into this business to to to help people and so it's it's when you when you work for years and years and years and and it doesn't translate it it it's can be frustrating but but now I'm excited that I it seems that the things we've learned that all of us have learned in neuros science is starting to now translate into some into something and in Neuroscience what's sort of what's happened the last 10 years is we' we're thinking of the brain and in kind of grander scale is sort of it's overall organization not so focused on just this area or that area um when I when I talk about the frontal loes as being the most important part the the you know the uh conductor yes I I I am talking about one brain region but it it's a brain region like I said that's connected to everywhere and it's because it's connected to everywhere is what's really um the essence of why it's it's so important so uh some of the research I'm excited most about sort of taking away the names of areas and just thinking about the brain as a as a a big Network like like an airline Network or or electrical Network and how how different areas communicate with each other and when you think of it that way so for example an airline network uh you've got all these hubs all over the world all over the country in the United States for example you've got Chicago is is is a hub and and there's other Hub Milwaukee or Cincinnati but they have very different functions in the network as a whole right if if you're trying to get from uh New York to San Francisco which happened to me many times even though you're not going through Chicago if Chicago is shut down you're probably going to get delayed because it just has this huge impact on the whole system and you know if Milwaukee goes down you don't even know it you just fly right over the I'm sorry if anyone's listening from there are probably a few you kind of go through but but so thinking about the brain the brain is the same way the brain has these hubs as well and and you know the prefrontal cortex is is a hub like Chicago it's just an important Hub that keeps the whole system uh going and that's why it has much more of an impact when you when you when you damage it or you stress it as opposed to some other part of the brain and so what's exciting to me is not only is that making us thinking about disease differently because now we're starting to think about how is diseases affecting these hubs that the pathology seems to be like when you look at Alzheimer's disease and you look at schizophrenia and you look at a lot of diseases it's not just that there some microscopic change in some neuron it seems to be affecting hubs in the brain that are affecting the whole network and so we have a different Target to go after for treatments what what can we do to sort of boost you know a hub that's been damaged as opposed to thinking about it in a in a less specific way and then also as we've as we' really start to learn about how the the brain is organized in these networks we've also learned that measuring uh your network structure is very predictive of of of your well-being and how you respond to interventions so there's a metric called modularity which measures um how organized your brain networks are and the brain is made up of different modules uh different networks and these networks can either be very communicating with each other or not so communic communicating with each other and and the more segregated they are we call that more modularity they're kind of separate entities they're they modular and it turns out we can measure that with fmri we can put someone in a scanner we can do this resting uh fmri scanning and then we can measure how modular your brain is versus my brain and all of us are very different levels of modularity is it more advantageous to have more modularity as opposed to less yeah it turns out that it seems to be more avation have more so we can predict more separateness of brain of function between areas yeah that the networks are sort of more independent that doesn't mean they don't talk to each other but at at at sort of Baseline they're more independent resting state connectivity yeah they're they're more they're more independent as opposed to uh less independent with each other not unlike uh neuromuscular Junctions during development are what we call poly enervated uh that's why babies can move their limbs but not with a lot of coordination look at a one-year-old trying to eat spaghetti for instance it's hilarious look at that same kid 7 months later there's a lot more Precision to movement largely due to removal more modularity of con connections right right interesting so we we did a study where we took 12 traumatic brain injury patients and measured the modularity so you get a a number you know you just get a modularity index for each of the 12 people and then they underwent this goal Management training and we were able to predict who was going to improve uh on the training that those who had more start started off more modular benefited more from the training and it's turned out that this has been a very robust finding across studies now across different training uh different young old patient populations it's also predicted things like um whether someone in a coma is more likely to do well or if someone who's older is going to have a certain amount of cognitive decline or someone's going to respond to behavioral therapy if they're obsessive compulsive so there's something about this brain St that not only we can measure but actually is giving us insight into the interventions that we're doing which again is going to be much more helpful in determining what helps and what doesn't help if we know uh we know sort of what the state is before we start the intervention so interesting and um makes me think many things but um I'll just focus on two of them one is I love this idea that you and others are starting to look at brain network activity as opposed to overemphasizing the role of say prefrontal cortex or hippocampus understanding more that those are hubs in a larger theme of um of activation because you know if I had one wish for science communication it's that people would yes learn some terms like dopamine and frontal loes it is important to know the nomenclature but to understand that if you really want to be able to work with the information in a way that's beneficial you need to think about verbs not nouns right it's about the action states of these areas at those action states are always um involving multiple areas just like you can't talk about running as just like quadricep and hamstring flexion and extension you know and contraction it's just it just you can you can break it down that way and it's useful to know that but ultimately you're talking about gate and stride and things that that have a real verb action to them and we haven't had so much of that for the nervous system at a at a circuit level we've been able to do that for individual neurons that's the first piece and then um the second piece is that you know it occurs to me that there's so much Rich understanding of the different states of sleep you know Matt Walker was just here recording this series on sleep that we'll release later this year and you stages one two three four deep sleep slow wave sleep rapid eye movement sleep but we don't even really have a naming um system for waking States like we say Focus we say task switching but those are um just names we made up uh just as stage 1 two 3 and REM sleep are names that we made up but there seems to be a much richer understanding of like what rapid eye movement sleep is good for and what deficits in rapid eye movement sleep lead to then there is for instance how uh given I Network G I'm going to make this up like calling a certain Network activation State like State a like we we the I feel like Neuroscience is tasked the field of Neuroscience now is tasked with with giving us understanding of the verb States and like what like these waking states of Mind are very mysterious and and for the general public this is important because people wonder like is my focus poor or is it is it good is my Tas switching ability good I mean we only tend to look at you know are they functional enough to do their job and manage their family manage their lives we don't really have metrics but for sleep we have metrics and Commercial products can measure that you know sleep tracker Rings wristbands mattress covers that I mean this sort of thing well you know yeah I I think modularity can actually be that metric some Metric of of your large scale organization of your of your brain can be that metric we we've there's a number of labs that have done this have measured modularity in real time so what I was talking about were just getting a snapshot of this is what your Baseline modularity is but we can also look at modularity how it changes on a second to second to minute to minute basis and um one of my forign post SE she just did a very simple experiment where there were nois there were sounds and the the functional my scan is very loud so you you can't hear very well but every once in a while there'd be a sound that was just above the this the level of the noise of the of the scanner and all you had to do was sort of uh you know press a button if you heard that sound and you didn't pick it up all the time you know you maybe 80% of the time you heard and sometimes 20% of the times you didn't hear it well she measured their modularity on a momentto moment basis and she could predict if they were going to get that if they were going to be correct or not and wre and and wreck the sound before they they got the sound if they were highly modular boom they they they got it if their brain had gone into this kind of you know diffuse less mod State they they missed it and so I could definitely see as you're talking about where if we could develop a modularity metric in real time on a device uh this would be GameChanger and so and that's sort of what I'm you know what I've been interested in do what's excites me is that we're not going to do with a SC obviously you can't walk around with a scanner in your head right and and even I don't think you could even do with the EG I think can we develop a proxy for modularity with some more simple way of doing it can we extract this maybe out of heart rate variability or for oxygen um I've been I've been working uh with uh some colleagues the a former student uh uh Brian Miller and postdoc of Adam gazali's West clap who have a company called Nur scouting where they are able to um they have we've been sort of doing scanning and also collecting physiological data to to try and determine if there's some Pro we can measure the modular and the scanner but can we pick that up in the in the physiology data because they can collect you know oxygen and heart rate variability and and other metrics that may be kind of a readout of that and then then we'd have a brain state which is what you were looking you know you're looking for some brain state but it's not I think people are thinking we're we need a helmet or something like that we need just something simple right that reads out brain State just the way we read out other physiological uh information from our our watch or or something like that well the Sleep trackers of various kinds have certainly been able to pull out information about rapid eye movement and other stages of sleep I mean key metrics not every metric not what you would get with person wearing a EEG uh you know probe or something you know set of probes but C information that can be used um one thing that has me a little bit perplexed um and uh I'm almost reluctant to bring it up but I'm going to do it um is that I did a couple episodes about psilocybin and the use of um Sil cybin for the um treatment of depression this is Robin cardart Harris from UCSF and I also did a solo episode emphasizing of course this isn't recreational use we're talking about we're talking about for treatment of depression but there there's a lot of neuroimaging about um of patients before and after U macro do cocy and this isn't micro doing and one of the major takeaways is um increased resting state connectivity which by virtue of what you just described might not be ideal for cognitive function it might be good for um social emotional function and I'm certainly don't want to disparage the beautiful work that's being done there but you said that increased modularity predicted improved function especially with cognitive interventions uh Sil cybin seems to uh induce fairly significant Inc increases in crossmodal talk between brain networks in other words less modularity so um should we be concerned no it's just it has to do with how we uh make these measurements and and connectivity doesn't mean the same you know there's different types of connectivity um and so I like to when I think about connectivity we talked about this connectivity of of a brain State and versus a brain trait so when we're talking about you being highly modular as a trait uh that's very different than what your modularity is like in different states it it actually turns out you do when you do these highly executive demanding tasks you get less mod you get less modular because you have your networks are communicating with each other so it's important to be for networks to get less modular when it's a more demanding task but that's very different than than whether what's your you know what's your Baseline modularity I see because it's you got to get from your your you know where your Baseline is to this other state and a lot of it has to do is like going from one state to another not not so much sort of the absolute sort of differences so that's that's interesting I didn't know about those results but it's interesting that uh that it does affect sort of connectivity in that way I think the drugs that are going to be helpful are going to are going to promote sort of networks talking to each other as opposed to networks not communicating with each other in your clinic do you ever combine drug therapies cognitive training and things like transcranial magnetic stimulation do you use stimulators yeah so I think um you know I have a lot of patients that I've referred for uh for its approved use which is depression so I'm very excited about sort of the the work that's being done with it as a as a for depression but we haven't really had any improved uh anything that's been for um you know for cognition so there there are bunch of studies anotal small studies where you can give trans simulation frontal cortex and working memory improved but they really haven't been done in ways that are we don't know if it generalizes if it's if it's going to be how you know the way it's been done in depression in a way that can really be but I but again it's just a matter of doing it I think it will be part of the things we do drugs TMS um and all the other things we've talked about it's not just going to be one one thing and and it gets back to networks right what this is doing is really changing how nodes you know the the interaction of regions it's not about sort of just increasing or decreasing activity in some mysterious part of the brain it's just sort of restoring the balance of a of a of a network well Mark I just really want to thank you you um you g given us an amazing tour of uh basically five Fields I threw a lot at you um you know as a neurologist but the way I'm I I'm slightly reluctant to do this but um I'm going to tell you a joke um that was told to me um uh so that there are these people stranded on an island and um they're they're really stuck and they're running out of resources and um by the way this joke was told to me by a physician and all of a sudden this hot air balloon and comes over and they're like my goodness so they start they write help in the sand and they you know and um hot air balloon directly over them kind descends almost you know almost to them and um and then someone in the hot air balloon says you know I'm doing the measurement and it's exactly 76 feet down to those people and then the hot air balloon takes off and goes away and the people on the beach one of them is a physician and he goes those were neurologists I tell that joke because that was the old school view of Neurology that um neurologists were great at describing things talking about the terrible conditions they could observe in great detail but that they uh did not do anything about it you on the other hand and I'm guessing others in the field but certainly you have proven today that you that joke needs to be revised whereby there's one at least one neurologist who casts a line down and and shimmies down in a assists them and and pulls uh those uh stranded uh people on on the island up to the uh the balloon because uh today you've described the the underlying nature of some of these things like working memory deficits traumatic brain injury concussion Alzheimer's Parkinson's again I threw a lot at you and you you responded with in in thorough clear detail but also a number of things that that clearly can assist in these in these um in these situations such as bromocryptine mindfulness exercise and uh and really as a as an exploration of of what can be done interventions and so um for all those reasons and for tolerating this terrible joke that I just told um I want to say thank you because um I've learned a ton and I know the audience has learned a ton and much of what we've learned has us um looking in the directions of of possibility to to alleviate these situations and and as you point out for the already healthy even to optimize brain function and health so for all of that thanks for uh sliding down the Rope to the to the island well I'd say you know on behalf of all the neurologist in the world thank you for appreciating what we do it's just it's just so important to try and get this message apart like I said you know with patients we just try to have them understand what what it is that they're going through and I think today patients have to really be advocates for themselves and so I think the more they learn about all of these possibilities the more they can go back to their their doctors or whoever and try and ask for you know what about this what about that is do you think this would help me because we have to be advocates for our own health and and the only way we're going to do that is just make people understand what it is that the possibilities are so thank you it was a lot lot of fun a great time well Amen to all of that and uh hope to have you back again thanks so much you're welcome thank you for joining me for today's discussion about the brain mechanism of cognition and memory and how to optimize cognition and memory with Dr Mark desposito to learn more about Dr desposito's work please see the links in the show note captions if you're learning from Andor enjoying this podcast please subscribe to our YouTube channel that's a terrific zeroc cost way to support us in addition please subscribe to the podcast on both Spotify and apple and on both Spotify and apple you can leave 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