[Music] so we're going to start uh in a moment with um Dr Tavi Choy Octavio Choy um I'll say I saved my sort of thank you now for him um Tavi uh is also the reason that we're having this program um he is you'll read in your bio uh about him in the briefing book um just one of the the premier upand cominging um psychiatrist and neuroscientist trained both as an MD and a PhD uh Tavi is um one of a new wave of um of doctors who are um you want to change your slides who are um uh introducing Neuroscience into their clinical practice as well Tavi um directs forensic uh Psychiatry uh here uh in Oregon Works intensely with the criminal justice system um and is going to get us kicked off with the really basic question of how does the brain work he has the toughest job of the entire day I told you tens of thousands of people are trying to figure out we're giving him about 40 minutes uh to get us up to speed uh but if there's one person who can do it it's Tavi and with that um let me hand it off to you he microphone microphone's working uh this is actually probably the toughest talk I've ever had to put together trying to explain the brain in 40 minutes um and so uh let's get to it so I'm an assistant professor at OSU uh and I am the director of the forensic evaluation service at the Oregon State Hospital in that capacity I have the privilege of living neural law boots on the ground evaluating criminal defendants uh with various types of medical and uh brain conditions and assessing how responsible they might be for the offenses um so let's start with a case that um of something that you might all be in a position of considering uh imagine there's an defendant who was causing a public disturbance was urinating in public uh swearing in public and uh this is a 25-year-old man um no criminal history excellent physical health never miss a day of work in his life alert oriented aware intelligent using language and very well good memory intact memory could learn new things and basically when you ask him about why he did it he just says well I don't I didn't care I just didn't care now imagine if two months prior to this incident a tamping iron 13 in 13 lb 43 in Long inch and a quart in diameter shot through his skull and penetrated the front of his brain would that uh kind of affect the way you might think about how guilty this person might be for their ax might that in fact be a a strong reason for why they this person behaved the way they did uh a lot of you are smiling and nodding your heads many of you know this is the famous case of Phineas Gage the most famous uh patient in Neuroscience I think half of cognitive Neuroscience textbooks start with the story of Phineas Gage so uh who is Phineas Gage he was a railroad Foreman back in 1848 suffered a terrible accident and uh from the Boston Post he reported it a foran in a railroad and Cavendish was uh tamping down you know he was exploding rocks to make way for a railroad track and uh you have to put you know gunpowder or the explosive and you Tamp it down with a tamping iron which caused a spark in the Rock and it exploded and the tamping iron was driven through his um through his skull uh you know 100 years later um back in 2004 uh spinus Gage's skull is currently at the Harvard Museum uh and the doctors has got his skull imaged it in a 3D in a cat scanner created a 3D model of the skull and was able to digitally remaster exactly the path uh of the of the tapping iron so this is just uh showing off that you know we have the skull we're kind of creating a bunch of three slices uh with this cat scan and reconstructing with the computer to make a three-dimensional model that's completely accurate in every detail this is part of the computer Revolution with increase in computing power you can take these two-dimensional slices and make threedimensional models and there you see uh the tapping iron going through the skull ouch uh now the amazing thing one of the amazing things about um phas gauge is that he survived and in fact he was treated by a physician named John Martin harlo who became famous by reporting on the case of Phineas Gage and here's what he had to say I'm going to just read this because he's such a good writer the equilibrium or balance so to speak between his intellectual faculties and animal propensities seem to have been destroyed he is fitful irreverent indulging at times in the grossest profanity which was not previously his custom manifesting but little difference for his fellows impatient of restraint or advice when it conflicts with his desires at times pertinaciously obstinate I love that yet capricious and vacillating devising many plans of future operations which are no sooner arranged and they are abandoned in turn for others appearing more feasible sound like anyone we know I mean a lot of us who work through you know with the uh criminal defendants I mean this describes a lot you know kind of very impulsive uh kind of personalities but the difference with Phineas Gage is that before his injury although untrained in the schools he possessed a well-balanced mind was looked upon by those who knew him as shrewd smart businessmen very energetic and persistent in executing his plans of operation in this regard his mind was radically changed so decidedly that his friends and acquaintances said he was no longer gag now uh you know fenus Gage is often pointed to as sort of the start of the birth of modern cognitive neuroscience and why is this he was really for the first clear example written in the literature of someone who suffered a brain injury and had very specific impairments which pointed to the key principle of the brain that different parts of the brain do different things so if you damage different parts of the brain there'll be specific impairments that result so the key phrase um is the equilibrium or balance between his intellectual faculties and animal propensities seems to have been destroyed so his intelligence as he was thought of back then was intact his memory was intact he was was able to have a conversation with you he knew where he was he could learn new things all that stuff was intact uh and also his emotions were intact he was able to feel happy and sad and all those things but the balance between those two things were was destroyed and I would argue that the best way to summarize Phineas Gage's impairments uh his brain deficit was that his conscience was impaired by that specific brain injury so what is a conscience anyone want just want throughout his conscience was was impaired in my opinion just my opinion but so what what do we mean by conscience Jim Cricket jimy what about jimy Cricket oner okay so it kind of you know helps you the right between the wrong and is it a jimy cricket where it's a cognitive thing where it's like you know the rules are wrong or is it like an emotional thing that stops you from doing what you think is right or wrong it could be both but what do you think is more important yeah anyone have this thing where you know you're in the middle of a you know kind of a deserted town in the middle of the night and you're stopped at this traffic light at the red light you know there's no cops around right but what what do most of us do we're glued to that to that red traffic light right we're not going forward even though we know there's no chance we're going to get caught so what is it that's stopping us the limic brain okay but explain it for people who don't know what the limic brain is it's that gut Consciousness that you can't it's feeling and it has no cognitive skill building it's just a feeling yeah I would argue that it's sort of like this bad feeling in your body that you get automatically when confronted with these kind of kinds of dilemmas and it's that bad feeling I would argue might be more important than the rational I know this is wrong kind of you know cognitive thinking so uh you know the weird thing or the interesting thing about Phineas Gage is he seems to have suffered an injury that impairs that part of the brain which allows you to call up bad feelings in response to something that you know is wrong so we'll get back back that back get back to that in a moment but let's just go over some basic neuroanatomy so this is the picture of the brain that you know many of us are familiar with um you know this is a cerebral cortex you can see this is tough with a split screen I only have one pointer so so uh you know this is the Cal cortex we can see that it's um this is the surface of the brain we can see it's split into various loes there's the frontal lobe in the front there's a temporal lobe next to the temples the back of the brain is called the cipal lobe and the pral lobe is in between um and here is a top down view so we're looking from top down you can see the eyeball so it's like the brain is paint pointed this way and you can see you know an odd thing about the brain is that you know like the left the right side of your brain controls the left half of your body and the the left side of your brain controls the right side of your body so you guys probably know people who have suffered strokes and the interesting thing is that the that the side of the injury often results in deficits on the opposite side of the body these two halves of the brain are connected by a bridge called the Corpus colossum it's a huge uh series of connections that connect the right and left halves of your brain uh and coffee brg asked me about split brain experiments and you know neurosurgeons have actually cut this bridge it turns out what happens is that that splits you into two different people that live in the same body so it's a really fast fting thing that we're not going to go into more in this talk but um there's a big bridge called a corpus kosum and then this is a picture of the brain looking as if the brain is looking right at you and so you can see the Corpus colossus's bridge and you can see that there's stuff buried underneath the cortex right uh so that's a really important point so the brain is not just what you see on the on the surface there's stuff buried underneath there oh another thing is you can see that the brain has lots of convolutions and the bumps are called gy and the dips are called suai and why do you think we have all these convolutions and dips and suai and stuff like that what does that do increase the surface area right so if the brain is a computer you can pack more Computing Machinery into that same area and actually if you look evolutionarily these are different kinds of primates and the relative sizes so here's humans and we have the biggest brains but we also have the wrinkliest brains so when you look back in evolutionary history the brains get smoother and smoother uh so it's a very interesting thing that we get more brain Machinery stuffed in there by all those f so okay so another key point is that the brain is a multi-layered structure it's not just the cortex what you see on the surface there's lots of Machinery underneath there um so a lot of us know about this Theory called U the Triune brain which is put forth in the 7s um by a Harvard psychiatrist named M mlan basically he posited that when you look at the Modern human brain you can you can conceptualize it as being constructed of three different layers what do you call the reptilian layer the lyic system and then the neom ion which is cerebral cortex so if you look at a MRI and here's the nose looking forward here's the brain uh we consider these this first most primitive part of the brain to be called The Reptilian complex which is the brain stem on top of that is built a series of structures called the lyic system and on top of that we have the covering called the the cortex cortex literally means covering so okay so here's the cortex and what the cortex in general does is it manages all the computations required for higher cognition stuff like language stuff like high order object recognition telling the difference between a Vango and a and a rembrand uh Consciousness being consciously aware of your thoughts consciously aware of your feelings all that fancy stuff that we consider being human is tends to be um computed and instantiated in the cerebral cortex if we get rid of that upper layer we see underneath it a series of a very complex series of structures that I'm just going to simplify and call the lyic system for the hardcore neuroscientists I know that that's kind of a simplification but let's just call this middle layer the lyic system and what this kind of you know and lyic system does many things but one of the key things it does is core evaluation so you know our brains evolve to Keep Us Alive and what the lyic system does with core evaluations is it scans everything on the outside hearing s sight sounds touches uh feelings inside our body and it just scans for anything that you might want to pay attention to because it's going to help you survive so things like donuts things like spiders like sexual partners right so um if it sees you it's constantly scanning if it sees something that that's going to help you survive in some way it goes dinging linging Ling and tells the cereal cortex so then you can actually go towards that donut away from the spider away from right and it doesn't and you know that that message what does that message feel like it doesn't feel like a message a text message coming up on your phone it feels like the feeling of craving like the feeling of you want to go towards something or feeling of Terror or fear to move away so these core valuations are computations done at a very low level that scans the entire external and internal uh environment in order to give your cerebral your cortex a signal to to move towards things or move away from things and those signals feel like feelings under if we get rid of the lyic system um underneath that we have the brain stem which has bunch of basic life support so the brain stem is actually the upper extension of the spinal cord can you guys see okay here I I feel bad because my pointer doesn't show up on this thing so I'm sorry maybe I'll we'll do like a Bono I went to a YouTu concert and you know a circular stage the half this Conant is this way and the other half VI was this way so maybe Midway I'll switch over so the brain stem is the upper extension of the spinal cord and it handles a lot of basic life support there are centers there that control respiration and heart rate and basic sensory processing uh there are sensors there that are constantly sampling the chemical environment of your blood to make sure there's enough oxygen in it for instance so lots of basic life supports done there if you have a stroke in your brain stem you generally die like you know you don't have breathing you die okay so there's the brain stem on top of that we have the lyic system that is kind of constantly looking out for things at a low level to help you survive core valuations and on top of that we have this H thinking brain the cortex now another key principle that the brain is hierarchically organized so you know you are not aware of most of the things your brain is doing right anyone here consciously beating their heart or you know can you forget how to breathe not really right that's because your your brain the lower centers the brain stem the limic system they're doing lots of things underneath your underneath Consciousness they're helping you stay alive and your coach is only notified when it's just like a corporation you have your underlings do most of the grunt work answering the lowlevel emails and anytime there's something hm you know I think the boss needs to know about this because there's two conflicting emails and not quite sure how to resolve it that that then gets bumped up to the next level of the hierarchy so for instance your brain syst has basic life support systems uh including sensors for oxygen levels in your blood so if there's a low level of oxygen in your in you know the oxygen level in this room drops down these centers are going to start getting very excited saying H there's something wrong here something wrong here I need to notify the boss the brain stems boss is the lyic system limit system is is is it's monitoring everything even stuff outside of your awareness and that that's really cool like you're you're not aware of you know the feeling of you know the air on the back of your left hand right I mean now you are but you weren't before but I guarantee you if there is a feeling of some fuzzy legs walking on that on that AR suddenly syst would say this is important I need to tell the boss and you become aware of it okay so if you have Dro an O2 that tells the lyic system Lim system is sampling lots of things including the feeling in the back of your hand but if it gets a message saying your O2 level is dropping it says I need to tell the boss about this this just can't go on right and so then it sends a signal to the cortex Cort cortex says yes oh I do feel like I'm suffocating and so I'm going to get out of here and possibly go outside but please stay in the [Laughter] room so uh this is a busy diagram this is um a diagram from one of the um references that we put in the briefing book uh one of the latest issues um articles about the brain circuitry um of drug addiction and so uh you know don't get overwhelmed it's easy to get overwhelmed with these has of diagrams I just want you to pay attention to three different areas the amydala the vental striatum and the orbital frontal cortex right so have to give some love to this side the amydala the vental striatum and the orbital frontal cortex now the amydala and the vental serum are part of the lyic system doing those core evaluations the amydala tends to be scanning for things that could possibly be threatening to you and you need to move away from and when the amigdala activates that feels like fear get away the vental striatum is is uh Cally known as the pleasure center of the brain and these are all oversimplifications every brain area kind of does everything but just to keep things a bit more simple the vental starem it's called the pleasure area of the brain and it tends to be looking out for things like donuts sexual partners it gets excited when it sees things that you might be interested in moving towards and that feels like pleasure feels like anticipation if it activates and the thing isn't there like if you're C if you see you want a donut but there's no doughnut there if that activation feels like craving now um obviously you don't want to act on every single impulse your amydala and eventual strim is saying you don't want to you know unless you're a presidential candidate you uh you know you see an attractive sexual partner you're gonna you know you're GNA generally want to say you know I I couldn't resist I'm sorry um but that's where your cortex comes in so your orbital frontal cortex is involved in evaluating the signals coming from the amigdala and the vental sprum saying it adds context to what those drives are telling you to do it says well maybe not maybe we shouldn't go you know grope that person or maybe we shouldn't have that you know six donut you know um or you know the amydala is like a little it's the amydala is like a scared little kid that everything freaks freaks you know that little kid's out you know so sees a spider and the midd goes oh my God there's a spider there's a spider it gets very active and excited and the orbital frontal cortex adds context it says you know what there's a cage around that spider we're actually in the zoo so you don't so calm down Amiga it's going to be fine or you know you know the vental stum gets very excited you know seeing a dut and the fral square just says you know the last couple times you kind of did overdid it with the donuts and you felt really bad uh so it kind of helps modulate and inhibit those drives that come from underneath in the limic system well guess part what part of the brain was damaged in phineous gauge the orbital frontal cortex the tamping rod went straight through that area that's the area that gives emotional context to the drives and can inhibit appropriately the drives that should be inhibited uh and so uh Antonio deasio and his wife Hannah Antonio deasio is one of the Geniuses of Neuroscience he's a neurologist I don't he used to be in Iowa I'm not I think he's he's moved around he's at USC now some great Folks at USC um and he did a he studied this area the brain called the vent so it's the orbital fral cortex his phous gauges tamping iron it went through and here's a side view of the brain with the brain looking forward this way and then underneath the vental surface of the brain eyeballs be here so you're looking underneath this section of the brain is called the orbital frontal cortex it's also called the ventromedial prefrontal cortex that was the area those damage and Phineas gauge and he um his lab was really instrumental in studying stroke patients to understand what this part of the brain was doing because the fascinating thing is if you damage this part of the brain your memory is fine you know you know where you are your use of language is fine your cognition is fine and also your emotions are fine they're able to feel happy and sad but they no longer seem to care about uh about inhibiting things that we would find socially kind of repulsive right so I would argue that that's what keeps us from urinating in public even though we have a really full bladder we're just not going to do it the reason we don't do it yeah we know it's wrong but the other reason is we know we would dive of embarrassment right and that feeling is it's a feeling that stops us it's this feeling of I feel really bad in my body contemplating doing this and that's what generally stops us from doing things that and where did that feeling come from how do we get that feeling in our brain were we any of you have babies do they have problems urinating public AB we learned that right it's a series of learned emotional respon it's like you did something you're in public and then you felt bad somehow mommy said don't do that and you felt bad in your body over time you developed an emotional linkage of an state of your body with a certain context that is exactly what this part of this brain is doing so um people with damage in this part of the brain they have something called emotional Amnesia they can feel emotions but they just don't store it so they can't form those linkages between a context and a feeling in their body that would ordinarily stop many of us from doing stuff like urinating public or groping um people okay so deasio the way he put it is this area of the brain holds linkages between the facts that compose the situation and the emotion previously paired with it and I would say that is actually a major part of what the conscious is this is where this is one of the main brain areas where con the the conscience uh is instantiated okay and you know in general fenus gauge was an important case of some someone who suffered a specific brain injury and had a specific deficit thereby showing a key principle that different parts of the brain do different things that's principle is called functional specialization uh and actually the man sitting there Michael Posner is one of the key people who established uh that that principle on the brain and so uh you know this idea that different parts of the brain do different things that might sound like a really obvious idea uh to modern day people but it was not an obvious idea hundred years ago and in fact there was a raging debate between the holists and the localists uh so P Pier Floren was one of the main proponents of holism which said like you know the brain is a is a computer and all parts of it are undifferentiated so really you know impairments have to do don't have to do with the location of the impairment it has to do with the size of the impairment of of the damage right so every brain part is kind of interchangeable France Joseph Gaul uh was a opponent of localism they said no no brain areas are highly specialized okay different parts of the brain do different things but he took it a little too far he's the he's the main guy between uh for the theory of phenology uh which you guys know phenology right bumps on the surface of your head means you're criminal it means you're a good person I have a very bumpy head I don't know what that I uh I shaved my head to go into Meditation Retreat a few years ago and I was like oh my God I'm never shaving my that's why my hair is kind of like you know I I've God would hate me but he he took it too far you know he said you know the the brain is divided into areas and there's an area for acquisitiveness and there's a area for sublim whatever Sublimity is and an area for mirthfulness and he very there's one area of the brain that does that and that that's nonsense that's taking it too far um because when you think about it any task that you do like let's say you're reading right when you think about what that task involves it involves looking at looking at words so there's a visual system involv it right then you it's understanding the word so there's you know there's processing of what that visual signal means it might invoke memories right so and those memories might invoke kind of behaviors and decisions you want might want to make each of those different uh qualities of that task is done in different parts of the brain so even something as simple as reading a single word activates different parts of the brain uh associated with those Elementary tasks does that make sense and that's what Dr posner's work with his colleagues at the at Washington University established in a series of super elegant studies I I love reading those studies when I read those studies I feel like oh I understand the brain okay so actually the you know localism is taking it too far holism is also taking it too far there's this in between thing called distributed processing and that's the principle that I just elucidated where you know it's not that there's one part of the brain that does you know a single thing but there you know any task that you have has Elementary cognitive operations and each of those Elementary operations are done by different part of the brain does that make sense so it's a collection of specialized modules that get gets invoked dynamically depending on the task that's at hand right okay good nodding heads good um now um phas gauge was a loss of function study uh you know a tamping iron went through a certain part of his brain you know and he lost some ability and so people started to make correlations between parts of the brain and the and the parts and what you know what kind of functions that uh are done by that part of the brain uh many of us are probably familiar with Strokes Strokes um stroke patients so that's another loss of function study where part of your brain gets knocked out and by studying what kind of impairments result from that you can make inferences about what that brain area is useful for right make sense uh in fact you know some of the seminal studies um early studies on brain localization were had to do with aphasias or language deficits and so you guys heard of broka and wariki these are two famous scientists neurologists around the turn of the century who studied uh some fascinating par uh patients who had language deficits in different parts of their brain let me go over here for a little bit so broka Pier uh uh broka was a French neurologist who found that a bunch of his patients lost the ability to vocalize language so they could understand language when you spoke to them and they could do execute command you know you know if you said set them for them to do something indicating that they understood language but they were they had a really hard time generating language and speaking so he discovered that these patients had a damage in an area of Cortex called broa area and interestingly that brokus area is right next to the part of the brain that controls the motor muscles of the lips and tongue so damage to this area um results in impairments where patients can understand language but they have a hard time generating language is it boy is it that Landing [Music] down it's hard to hear this person having a whole lot of time expressing language cookie jar you wouldn't call this person fluid right she has damage in broke his area now there's another area called wor Niki's area which is close to the auditory cortex where it uh with the part of the manand process is uh incoming sound signals damage to the W's area results in a language deficit in which people can generate language just fine they're talking up a storm but once you but they can't understand language spoken language they can understand written language which comes in through a different pathway through the visual cortex but they can't understand spoken language so when you ask them to do something in a verbal command they respond with very fluent nonsense so here's an example what are you doing today we stayed with the water of here at the moment and talk with the people for them over there they're diving for them at the moment they'll save in the moment heal of water very soon for him with luck for him so we're on a cruise and we're about to we will s right here and they'll save their hands right there for them so that's brok's area so those early studies were super uh interesting and important for establishing again the different parts of the brain do different things um s also around the turn of the century a guy named broadman uh had a microscope a novel technology at the time um and uh by studying he by stamping little core samples from different areas of the cortex and looking at them under the microscope he could see that cells look different in different parts of the brain and he hypothesized that the reason those cells look different is because those these brain areas are specialized and do different things so this is a broadman map and you might many of you might have seen this we still use this map of brain areas which he numbered like area 17 is primary visual cortex and neuroscientists still refer to brokas areas uh so it's another indication that if you look at the at the microscopic level of different parts of the brain it looks different and that that that supports a theory that different parts of the brain do different things any questions so far or yeah this is all good okay so um now broka I should have I learned this thing trigger alert trigger alert I hadn't heard this before yesterday I need to warn you for anything that might potentially be traumatic um and my tone of voice was a little sarcastic I don't mean that um but um bernicki and broka um you know they discovered where the where the damage was in their patients's brain by they had to wait until those patients died and then they had to slice up those brains literally with a knife and then find little goobers and stuff then like oh okay this you know this is seems to be where the problem is now you can imagine that's an incredibly slow process right like you have you know five really interesting patients and you have to wait 10 or 20 years until they die or you know unethically hope that they die sooner now wouldn't wouldn't the whole Enterprise be a lot more efficient if you could look to see where the damage was in the living person right that would be fantastic right and so that's what the Imaging revolution has done to help us um so I'm going to talk about s the evolution of brain Imaging so the X-ray we all know about x-rays invented or discovered by renen um he reported in in a a meeting in 1895 that he discovered these X-rays and this is the very first x-ray he took over wife's hand and you can see the ring and his wife was repeated to have said I have seen my death when she saw this scan now x-rays are amazing uh x-rays work by shooting um um high-intensity waves called x-rays through a person's body and on the other side is a photographic plate and then some stop x-rays more than others like bones stop X-rays and you know really well leading to light areas in the X-ray and tissues tend to soft tissues tend to stop them not so well they go through and so the photographic plate gets start so they're called shadow pictures um and here's a skull X-ray and you know the the dream was maybe we can see the brain with this x-ray stuff right but the problem was U the brain is inside this thing called the skull and the skull is a really dense thing that stops most X-rays and so it's really hard to see also with an x-ray a threedimensional thing is flattened into two Dimensions so it becomes really hard to tell anything apart that's why Radiologists get paid the big bucks they see something something this and they can they can turn that into a three dimensional image in their heads so for a long time the brain was called The Dark Continent we had no way of Imaging it now I think around the um 50s 60s someone had the body idea of of injecting air into the brain because air is very not dense uh and compared to brain tissue we might be able to tell the difference in the X-ray so the um the brain has a series of interconnected fluid canals called the ventricles right the ventricles make cerebral spinal fluid and bathe the brain in fluid uh someone had the bride idea of taking a syringe of air injecting it through the brain and injecting air into the system and then you'd be able to see the bubble of air with an x-ray later on people said you know we actually don't need to go right through the brain we can go through the spinal cord with a spinal tap kind of procedure and that was a lot better um but still these are the kind of images you get right it's going to be hard to tell Pro I me you can tell some if someone has a major problem with their ventricles you can tell something's going on but it's a low resolution image and I like seeing this to remind us how far we've come you inject the air bubble and then you they're in this chair that kind of puts you in different positions and then you take x-rays in those different positions as the air bubble moves to kind of this was supposed to be an incredibly painful procedure and the joke was that this uh this um procedure was uh therapeutic because the patient whatever their complaint was never came back to you again so this was the 60s okay um shooting ahead the CAT scan um it was invented in the 60s The Beatles were an incredibly important part of developing the CAT scan the CAT scan was developed by Emi which is also the record label the be the Beatles Emi ended up with a just a ton of money from the Beatles albums they said what can we do with all this money an engineer uh you know at Emi said I know what to do with that money with the rise of computing power I can develop a new kind of X-ray that will take a series of of x-ray images in in a rotational Manner and with my computer algorithms can reconstruct a three a two-dimensional and then a threedimensional structure of the brain um and um you know amazingly it worked so when you look at a cat scanner this is the inside what this is is a spinning x-ray where you have an x-ray SCE that's spinning in a circle and there's a photographic plate and it's taking like a million x-rays right and then magically if you do take a million different you know x-rays from different angles reconstruct that with the computer you can now start to look at brain tissue so this is the first uh CAT scan um and can you see see anything here there's a dark spot right there so it's fantastic it's always great when the first cat scan shows something you can actually do something about so this turned out to be a tumor that was reected uh and you know houndsfield went up went on to win the Nobel Prize and it it was all good uh the MRI is a technology that we're most of us are familiar with it's our modern Imaging method uh and it's a much bigger machine so here's a person here's you know and the MRI and it take you know hours of physics to explain exactly how it works works but uh suffice it to say that the MRI can interrogate magnetic signals all throughout your brain and because your brain is made of different different you know comp compositions of water and fat and different kinds of molecules it can actually distinguish those magnetically so those have different magnetic properties that can be converted to an image um and so and the MRI resolution is uh depended on magnetic field strength so the early MRIs were 0.35 Tesla then there were 1.5 Tesla then you went up to 3.0 Tesla then you went up to the modern research uh scanners have seven Teslas and if you compare the difference between the 0.35 Tesla and the Seven Tesla there is a remarkable Improvement in resolution uh the world's most powerful MRI is being constructed there's a that's a person inside there um it's going to generate an almost 12 Tesla signal which is just enormous and with that with that enormous magnetic strength the voxal or the brain elements that get get image gets smaller and smaller so we're getting incredibly we're going to get incredibly high resolution um pictures of the brain and like many big science projects keep keeps getting pushed back uh now that's loss of function studies um which are really useful but it's sort of a kind of like if you want to figure out how your iPhone work it's like if you took an ice pick and stabbed different parts of your iPhone and said oh well this doesn't seem to work anymore right it's kind of a slow laborious process so what we'd really like to do is study the intact functioning brain what is the normal function structure and function of the brain and so that's where functional Imaging studies come in and that's really a revolution so the two main ways to visualize brain activity these days are with pet and with epari uh and a pet studies are amazing and uh they can't and they can do things that fmri can't do I'm going to focus mostly on fmri which is used more uh pet requires injection of radioactive particles and a lot of patients kind of don't like that so much so fmri it's all done with magnets so it's safe and it's even holistically beneficial so fmri so the thing with fmri to really a key point is that you know although these pictures are very pretty and it looks like we're looking at brain activity we are not looking at brain activity we are looking at an indirect measure of brain activity we're actually looking at a vascular response to brain activity so the fmy visualizes a vascular response to brain activity not brain activity itself and so you know the principle is if a part of your brain is working hard it's going to recruit more blood flow that extra blood flow is going to change the magnetic properties of that part of the brain and that can be visualized on the fmri so the fmri actually visualizes what's called a relative oxygenation level which is an indirect measure of brain activity because your brain's working hard recruits more blood blood oxygen level goes up and that can be seen on the MRI now so uh this is an important slide and I you know I see the references in the briefing book in this you know there's many limitations of EP we're looking at a correlation of vascular response to brain activity and all correlations are imperfect and there's people who've made their careers studying how th those things can be mismatched uh the other thing to really understand is that this is a highly processed image this is not just a photograph of your brain activity this is a highly refined image with many steps and statistical assumptions behind it uh there's a lack of standardization so that one lab's FMI machine has a bunch of settings that aren't the same is another lab's fi machine so you can imagine if this gets into court and it's really been resisted in courts because you know one one lab's FMI you know image can look very different from another ones if all the settings are different right there hasn't been standardization in the same way that DNA analysis has been completely standardized from Lab to lab um and also some of the statistical assumptions have been shown to be faulty in fact there's a major paper this year that was incredibly disturbing to fmri researchers that showed that based on an obscure setting in the software of most fmri software packages that up to 70% of the results might just be BS so it's still a new technology it's developed in the 90s but it's still relatively new uh fmis is being used more and more in fact Sarah Fel Ying will um present I hope on her elegant studies showing or I'm not going to tell her what she's going to present but she's done very elegant work looking at adolescence engaging in therapy seeing what parts of their brain are active and using those FMI images to refine what kind of therapeutic interventions uh might be U the most effective so different parts of the brain do different things that's how we get these colorful maps that you can see if you open up any web page another key principle brain areas are wired together right they talk they do these different things and they talk to each other they form these local circuits right so this is a circuit that we've talked about already there's the amygdala the part of the lyic system that gets really excited over things that are scary the vental striem the part of the brain that gets excited over things that like donuts um and the orbital FAL cortex it says hey maybe we shouldn't follow every impulse that we that we you know that we might have and in fact you know what's uh hope what Dr Compton I think will talk about is how this circuit gets corrupted uh with as you develop a drug addiction when you look at the microscopic level of what these wires are composed of they're composed of a brain cells so here's a high resolution picture of a brain cell with a cell body a the wire which is called the axon and then the end of it which is called the axon terminal and so this is the basic Computing unit of the brain and you know what's what's interesting about this is that this is a chemical electrical chemical system so the dendrite has the cell body has lots of extensions that sniff around the chemical environment looking for things that it makes it excited chemicals that make it excited if it gets excited it generates an electrical charge that then gets sent down the axon in an electrical impulse at the other end it releases chemicals called neurotransmitters which then continues the brain communication that's why the brains are uh you can you can control brains with electrical you can put an electrode in someone's brain turn it on and see weird things happen you can also give people uh drugs right medications different kinds of chemicals and that will affect brain function that's because it's affecting the the chemical environment which gets picked up by the neuron does that make sense okay and this is a high resolution view of what the end of one axon with the start of a new neuron so here's a two neuron circuit here's the axon The Wire right and then it's connecting to the second neuron and this connection is called the synapse right so I'm going to show you a high resolution view of the synapse so the electrical impulse called the action potential comes down at the end it releases chemicals called neurotransmitters in this case acetylcholine those neurotransmitters diffuse across the synapse and bind to receptors so here's a re receptor it binds to the receptor and what that binding does is open up the pore which allows electrically charged uh molecules to come in which can continue the Electrical uh process uh here's an incredibly impressive example of brain wiring diagrams Carl daero is a name you should all be aware of he is 100% guaranteed to win the Nobel Prize uh one of the things his lab uh invented was a a method of making the brain Clear so this is a mouse brain and he made it clear once you make it clear you can fluorescently label uh brain cells and look at circuitry at a whole brain level so here's one of the really impressive videos from his lab where he's showing you the mouse brain he's showing you how they're taking two dimens you know two dimensional slices which they're going to feed into a computer to construct a completely accurate three-dimensional model high resolution model you zoom in you can see you know this is the whole brain these are the axons you can see you know axons coursing back and forth and it's all in the computer so you can rotate you can make parts of it transparent so now the computer's reconstructing the three-dimensional model which is then you can then rotate and you can then fly through the brain look at cellular level resolution I mean imagine this 100 years ago this is an incredible credible technology Carl diero yeah this is the part of the brain called hippocampus which is important for memory and again he's just slicing through these are the cell bodies you can see these wires are the axons here he's labeled different sets of neurons with different colors you can then take each slice reconstruct it with a computer make a three-dimensional model and this is not an artist rendition this is an actual part of the brain with all the wiring intact okay um in the in the human beings we can uh image this with diffusion tensor Imaging uh diffusion tensor Imaging allows us to see the wires in the brain does that because when you look at neurons they um they have water in them and water tends to go up and down the Axon DTI Imaging looks at the the movement of water molecules and from that you can infer um where the connections in the brain [Music] are so we have these very high resolution DTI Imaging maps of different um these are all the different kind of wires in the brain and we get we get those wires by looking at where molecu molecules of water are going back and forth okay I'm gonna just finish up with one last slide so I talked about the brain it does core evaluation you know the lmic system is looking out for things that helps you survive Donuts sexual partners spiders move away from move towards right and then the upper hearts of the brain the cortex puts those core valuation into context it's cognitive context saying well you know you ate your six dut and you didn't feel so good emotional context where you felt bad in your body when you over binged on Donuts before so it says maybe we shouldn't listen to the core valuation so much and that's built up through past experiences so if you see a donut you know your ventum goes dingl lingling ding lingling uh so that creates that feeling of Drive of wanting to move towards that donut and I'm from Portland so that's why there's so many donuts in my talk we have fantastic Donuts uh you know and that you know it brings up facts and reasons Donuts are good Donuts are Tasty Donuts have 8,000 calories it also brings up emotional context of these linkages of what happened and how you felt the previous times you eat donuts these are all connected in a circuit right and then from the activity of those of the circuit you come up with a with the decision eat or don't eat um and if there defects in either brain areas or their connections you're going to have impaired decision- making and a lot of what happens with drug addiction is that this circuit gets corrupted over time so you make worse and worse decisions I just want to make a shout out for this is the last slide so um you know how do we change the Cog the way we think about things generally with psychodynamic therapy with therapy kind of reframing what some with the cognitive mean meaning of something is right um how do we work on the emotional context well we have therapies like CBT which change the kind of emotions we actually link to a certain situation and um Sarah I might talk about her work or not but she's doing fabulous work looking at different ban areas that are activated by different kinds of therapy uh to guide what really what what's what are the active ingredients that make therapy effective now you can control the you know the co core valuations with medications and with new techniques that I hope our other speakers will talk about Mar and fireman are is going to talk about medications that it might affect the activity of these of these levels maybe turning down the vental stardum activity a little bit so you have less craving and Virginia kusan Carlson and Kathleen Grant I hope we'll talk about just some fabulous research using dreads which are uh designer drugs that can activate receptors in just specific very specific neural circuits to turn them up or down so imagine there was a tiny little spot in the vental spum that led to craving for cocaine imagine there was just one spot there imagine if you can selectively turn down the activity of just that one spot and get rid of craving for cocaine that's the promise of the the of the kinds of approaches that these guys are trying to do we have a great day ahead of us thank you so much for being here and it's a pleasure to to talk to you guys thank you