>> rose: welcome to our program. tonight, a special edition. the charlie rose brain series, year two. in episode one, we focus on neurological, psychiatric and addictive disorders. >> the brain is the most complicated organ in the body and therefore susceptible to more diseases than any other organ and we're going to begin by consideri psychiatric, addictive and neurological disorder which is encompasses all brain disorders and we're going to ask the question what are the similarities and differences between them the

situation changed remarkably in the last 40 years. a new synthesis occurred within psychiatry triggered in good part by basic science. first of all there was a philosophical synthesis when cognitive psychology, the science of the mind, merged with neuroscience, the science of the brain, to formulate a new science of mind. and as we discussed in the earlier series, fundamental assumption of the new science of the mind is that every mental process, from the most trivial ones-- get ago golf ball-- to the most sophisticated elaborateivect are mediated by the brain and we began to realize that all mental disorders, addictiveisorders, must be brain mediated. >> rose: episode one of th dharl charlie rose brain series 2 underwritten by the symons fodation coming up.

captioning sponsor by rose communications from our studios in new york city, this is charlie rose. >> rose: it has been said that the brain will be to the 21st century what the at tom was to the 20th century. tonight we continue our explo ration of this fascinating organ with our second charlie rose brain series. in our first season we studied brain science. this year we expand our journey to pro i would have a parallel view of brain disorders. for each program and disorder, scientists and researchers have studied the disease from both a medical and scientific perspective will join us. we will discuss disorders with patients, some are physicians. and finally we'll explore our

increasing knowledge of brain disorders and how it has enriched our understanding of e human mind. for tonight's inaugural episode, we study how neurological, psychiatric and addictive disorders result from disturbances in different neural systems. our understanding of brain disorders has evolved greatly throughout history. two centuries ago, mental illness was believed to be a disease of the mind, not the brain. those ffering from psychiatric disorders were thought to have defects in their moral integrity. in an attempt to you have toen them, they were subjected to crude and inhuman treatments such as bleedings or even rture. as tim progressed though, the perception and treatment of psychiatric and addictive disorders changed dramatically. in the last 40 years as synthesis between neuroscience and cognitive psychology helped us understand the mind as a series of functions carried out by the brain. genetic research and the development of brain image having clearly revealed psychiatric and addictive disorders to be biological

disorders. today we stand on the brink of a new era in brain study. joining know discuss where we are now and where we're going are a remarkable group of scientists. gerald fishbach is a professor at columbia university and the scientific director of the simons foundation autism project. thomas insel, director of the national institute of mental health at the n.i.h.. nora v cow, director volokow, and cornelia bargmann, a professor at rockefeller university. and my cost host is dr. eric kandel, a nobel laureate, a professor at columbia university and a howard hughes medical investigat. we begin our program wh the question what other similities and differences of various brain disorders. >> in this issue we're going to consider various various brain disorders and as you know the brain is theost complicated o gahn in the body and susceptible to diseases than any other organ

and we'll begin by considering psychiatric, addictive and neurological disorders which encompasses all brain disorders and we'll ask the question what are the similarities and differences between them. now, this is an issue that has been discussed for decades and thinking about it can be divided in three phases. the first phase which is called the moral face. continued until around 1800 when many physicians thought that only neurological diseases are based in the brain that psychiatric disorders and addictive disorders were not brain disorders, they were weaknesses of character, moral disorders. and people with dictive and psychiatric diseases were isolated from the rest of the community, put into ylums, put in chains and often treated very very harshly. needless to say, not only was it

inhumane but counterproductive. then the situation changed when a great french physician, 1800, filipe pin nell ce along and he changed things dramatically. he asserted ver strongly that psychiatric diseases and addictive diseases are medical disorders. they're not weakness of character. and that they need to be treated in a humane fashion. he removed the chains of ople in the great paris psychiatric hospital and he began to get patients to talk to him about their problems and interact with each other, almost the beginning of psychotherapy and group therapy. and he had the notion that psychiatry is a subspecialty of medicine, these are all medical disorders and he had the far sight to see these are a genetic

predisposition to people who are under social stress. this had an amazing impact on the field. the next phase began with a guy called pierre broker. >> rose: this is the an moll cal phase? >> exactly. you ow stuff better than i do for god's sake. we should change positions? (laughs) >> rose: i'm a good student. >> you're better than that. he was interested in a particular brain disorder called aphagia, disorder of language, and he was interested in whether that could be localized in the brain and he found first one and then a group of patients that who had a specific form of language disorder, they could understand language perfectly well but they couldn't express themselves in language. and when t died and came to autopsy h found that invariably that a lesion in the left side of the brain and in the front of the brain.

about 15 years later, carl verneky, a german neurologist picked up the study of aphagia and found a patient who had the mirror image clinical picture. he could articulate, could express language but couldn't understand it. when he died and came to autopsy he had a lesion on the left side and the lesion was at the back of the brain. he found the lesions of his patient and breaux a's patient are sbi connected. that led him to see that stlfs a lesion of a number sites that have been connected. people began to explore a number of neurological diseases and jerry fishbach is going to speak about that and saw that all of them could be localized to one or more areas in the brain, neural circuitry in the brain.

when psychiatrists beg to explore the brain for psychiatric as far as schizophrenia, depression, addiction, they didn't find vious lesions in the brain and so many thought that these are not brain-based disorders, these mental disorders. few far-sighted sky trysts realized they were psychiatric disorders but undetected. the situation changed remarkably in the last 40 years a new synthesis occurred within psychiatry. first of all there was a philosophical synthesis when cognitive psychology, the science of the mind, merged with neuroscience, the science of the brain, to formulate a new science of mind. and as we discussed in the earlier series, fundamental assumption of the new science of mind is that every mental process, from the most trivial one-- hitting a golf ball-- to the most sophisticated, lab aive

the, creative act are mediated by the brain. and, of course, psychiatrists began to realize that all mental disorders, addictive disorders, must be brain mediated. this was further advanced by two other mor advances in the field. one was beginning with franz coleman around 195 people began to realize these disorders have a genetic basis and that strengthened the biological underpinnings of it. finally imaging techniques came available in which nora and tom are going to speak about that made it possible to visualize even with addictive and psychiatric disorders areas in the brain that are functionally disturbed. so now we realize that these are biological disorders, and we need to understand three things. what do genes contribute? what does dwibting contribute? what does environmental factors contribute? and it's pioneered in how genes affect behavior a we'll see how we can approach that using animal models so we're in for a

terrific discussion. >> rose: let me begin with gerry fishbach. tell me about the notion of neurologicalystems. >> i want to talk about stroke because it points out how vulnerable this brain is. as eric said, it's the most complex organ in the body. probably the most complex phenenon that we know in the unerse. it's made up of over 100 billion cells and every one of these cells is worng hard. they need to generate enormous energy to maintain thei signal, their ability to talk to each other in the brain. and for this they need oxygen. and the oxygen is brought to them by the blood supply. you can put a tourniquet around your arm and cut off the blood flow for a minute, for several minutes. many of us have had our blood pressure taken and once in a

while th physician walks out of the room and forgets that the cuff is still inflated and even though you may be squeezing your hand, you're fine for up to ten, 15 minutes or longer. but if you cut off the blood supply to the brain for seconds, maybe even 30 seconds, that brain will not function any more. the phenomenon of stroke when the blood fly is reduced can be demonstrated if you think of the first line. there are blood vessels that arise near the origin of the heart and then ascend into the brain. and they deeply pervade the brain and keep supplying it with blood and oxygen. the brain is about 1% of our body weight b it receives about 20% of the outflow of the heart. shows you how critical th energy needs are. that's true whether you're active, thinking about things, paying attention to things or whether you're sleeping.

indeed, the brain is probably more active when one is not paying attention to a particular area, the brain as a whole so that if there is a clot in one of those arteries or slight hemorrhage in one of those arteries, the brain cells in the immediate area if not relieved within one or two or three hours degenerate. that's acute degeneration. the next slide will show you what broca and wernicke saw. the left is broca's area and the right is we wereky's area. so it's possible to close off one area and have a broca's syndrome and erexp aphagia or close off blood flow to the posterior and have a receptive aphagia, not understanding the words spoken.

so stroke is a huge problem. on a more chronicasis, the degenerative disease i want to mention is parkinson's. if you show the next slide, the part of the brain is deep in the brain, in the brain stem called the substania nigra and they make the neurotransmitter dopamine. these cells degenerate long before, years before there are any symptoms of parkinson's disease. before the faint tremors noted in the hand or stooped posture or slowness to initiate movement. but what i just want to mention that is really the subject of much study at the national institute of neurological disorders and stroke at the n.i. is epilepsy. and here for reasons that are many, the nerve cells are just firing, discharging impulses out of control.

and if you see these seizures, you see how dramatic they are. they're not necessarily associated with degeneration but they are devastating nonetheless. and i hope we'll have a chance to talk more about them as the program progresses. >> rose: one question about stroke. i think doctors have told me that if you get attention within two hours... >> yes. >> rose: you can minimize the damage. >> yes. >> absolutely. >> rose: and that's because? >> well, it's because there are interventions that may break up thclot that has lodged in the arteries but it really does have to be within the first three hours of the clot forming. and i'm glad you mentioned it, charlie, because i think these things are never done deals. there's always a measure of hope that either early intervention or later after the stroke in this case is developedor

recovery of function. but what you have asked about is thisery ear critical period. it's why one must be acutely aware of the early signs of a stroke. don't go to bed ifou think there's something going on that you suspect... >> rose: and the signs of a stroke are? >> well, they may be a headache, excruciatingly painful headache, they could be blurred vision, they could be loss of sensation on one se of the face, weakness. weakness over one arm. notoriously, if you remember that diagram over the blood vessels, strokes are very often one side or the other left or right. the strokes which involve the whole brain are truly catastrophic and a huge number of lives have been saved or there's damage for the stroke minimized because of this early intervention. >> rose: let me move to tom and talk about disorders in the

context of what we have said and what you look at. >> so we talk about mental disorders as brain disorders as well and here we've got a collection of really a few of theimood and sang sighty disorders. think depression, p.t.s.d., maybe obsessive-compulsive disorder. >> rose: p.t.s.d. is... >> post-traumatic stress disorder. psychiatric disorders like schizophrenia, sometim mania, bipolar disorder fits into that category. we've got eating disorders like anorexia and then there are disoers whether it's autism or atntion deficit hyperactivity. l those fit into the spectrum of what we call mental disorders and the key message is that these are brain disorders just as eric said. they're a little bit different, though, than way that gerry's been talking about them, because these are disorders that don't have a focal lesion. when you look at the brain here, you don't find an area of dead cells. >> rose: can't do an autopsy and find aesion? >> people have looked for years but in each one of these cases

what you find is there's nothing there on autopsy. and yet when you use brain scans the way we can now, as eric mentioned, we've got this enormous werhouse of tools to be able to look a the brain and how it functions and health as disease and we can see that there are circuits that aren't functiong right. so each of these disorders involves some part of the circuitry that's either hyperactive or inactive or the communication's down. we don't know, actually, whether there's because there are lesions that are mike stop that i n you can't see, maybe connections at the connection to the synapses that are critical, maybe the wiring is off. or maybe there'sust a rhythm problem. or maybe all three are happening at various times. but the modern view of this is that we what we've got here are problems with the circuit. we should take a look at depression because that may be the best example. depression, as you know, is very common. about... any given year some 6%

of people will really be incapacitated by depression. it's this serious when it happens. and when you look at depression as a disorder, as a brain disorder, what you find is that there are certain areas that clearly are active or overactive sometimes and sometimes underactive. and one that's gotten the most attention is an area that's in the front of the brain called area 25. we can take a look at it here on this image. hand this is an area that sits deep in the frontal lobe. it's... doesn't have more of a name at this point than area 25 because it's a bit of a mystery. we didn't know much about it until we started doing imaging scans. people with depression. and this was an area that showed up. but importantly, it's not the whole story. it's part of a circuit. it's a today in. it's an important today in in that circuit. the rest of the pre-frontal cortex, which is important for decision making and judgment and planning for the future is also involved. ass the variety of areas that

are connected. the amygdala, which we think of as the hub of emotion, the seahorse shaped area called hippocampus which is so critical for memory. and then an area called th ins la, which is an area that's very important for bodily somatic sensations. that may be why people with depression feel they're dead inde. the hypothamus is involved which why there's loss of drive, whether it's x drive or appetite in people with depression. these are areas that are important. because the treatment wes have, whether they're psychotherapys or medications hit different parts of this circuitry and it's become clear that if u change

the firing rate of area 25 itself that that can treat depression in people that haven't been helped my medication. >> rose: how do you do that? >> you use a deep brain therapy technique. we have that as a treatment for parkinson's and you go into this one area that looks like it's overactive. bestimulating near it it reduces activity and people will respond accordingly with a reduction of depressive symptoms and a true remission of the disorder. so this is a powerful demonstration that this disorder can be thought of as a circuitry problem. almost like an arrhythmia whereby changing t circuit, changing the rhythm you can get improvement in the symptoms. >> there are two other things that emerge from the thing that tom is talking about. this is helen mayberg's work. she was the one that introduce this deep brain stimulation. she also showed that in milder

forms of deflaegs do respond to therapy, she image it had circuit and she saw there was reversal in the abnormality so she could tell that psychotherapy reduces functional changes in the brain. it's really quite beautiful and in that case showed very similar changes to selective serotonin up take inhibitors. >> and it begins to tease this apart because her idea-- and it one that a lot of people are getting interested in right now-- is that depression is not one disorder. it's many different disorders that may sharecommon symptoms. but dierent parts of this circuit could be more or less active in different people and that may indicate who's going to respond to which treatnts. that a question we're vy actively investigating at this point. >> rose: let me turn to nora and talk about addiction. you talk about disorder a then addiction. >> addiction, just like tom was mentioning for other mental illnesss is one of the mental disorders and it's circuits and in the past we believed tt drug addiction was a result

of... eric was saying of poor moral character. what has been fascinating as we start to understand what are the changing on the brain is that that has given us enormous insight about what it sbils to have free will and to be able to and nord control over your decision because addiction is the loss of capacity to decide what you want to do and be able to carry it through. and in the past years we've done lots of studies and we know for example all of the drugs-- legal or illegal, biology doesn't make distinctions-- have a common characteristic which is that they increase the concentration of dopamine in areas of the braiinvolved with motivation. and this is the mechanism that nature created to ensure that you will do behaviors that will enable you as an individual and

a suspicious to survive. so by creating the sensation of pressure which is transmitted by release of dopamine, not only you have that experience but unbeknownst to you you get condition and what is conditioning? a deep memory and emotional part of the brain that would recognize that stimulus the next time you see it and what generate it is drive and motivation to pursue it. and you can see how extremely cler nature is. because that w if you ate the banana and it was delicious, next time you're in the jungle and you see it you have this drive to want to eat it. well, drugs hijackthat system. but they do it at a much more potent way than any of the normal stimuli are for. so result of that, it's not just the pleasure you're generating by liberating dopamine, but the conditioning. now with imaging, for example, we can directly go inside the brain of people and see what drugs have done into their brain and startore t t understand why

their behavior gets so disrupted and the first slide shows how we do it. it's quite simple. this is where you have the areas of the brain with reward and multiseparation. to the left is an individua when they are not taking a drug and to the right you seee th individual when they are taking a drug like cocaine which increases dopamine. then dopamine floods the brain and removes the activity. so this is understood right now the reason why drugs can produce addiction. and for many years, in fact, it has been believed until very recently that people were addicted to drugs because they were more sensitive to the rewarding effects of them, more pleasurable, there was more dopamine release. however when you apply these tools to look inside the brain and see if that is the case, which is the next slide, you show it's absolutely the

opposite. in the upper part, you see normal control images in the left with no drug, in the right with drug and you see that the red is going down because dopamine has gone up and has pushed the activity away. the lower panel shows people in are addicted to cocaine and you can barely see any difference when they are with or without drug. and that's because in an addicted person-- contrary to the belief-- that drugs can no longer produce large changes in dopamine. so then how do you then make sense of something like that? and that is the essence and thef adction. you have transferred the value of the drug into the stimuli that surrounds the drug. that's what we call the conditioning. and so in this image you see no effect of the drug in a person that's addicted but if you suggest them, seeing a person that they've taken a drug with, eing the personality of the drug, take a $10 bill with which

they may have snorted see what happens. and that's the next images. when you expose dividuals that are addicted to drugs to cue, this is no drug, you can see a control video that is no drug versus when they are observing a vidy this is fullof scenes of conditioned stimuli. you can see the radioactivity has gone down because dopamine has gone up. so that is why in many ways it's so extraordinarily challenging to treat people that are addicted because the stimuli has been transferred to condition environmental stimuli so that when they go to treatment, they don't want to take any more drug, they go back to the environment but their brain is wired like this to release dopamine the moment they see a stimuli, a person with whom they have taken the drug and that elicit it is enormous desire to take the drug and that's why they relapse. at the same time, in parallel to the shifting in that

hyperhypersensitive toy the condition stimuli, we know repeated administration of drugs damages the areasf t brain that tom was speaking about, the frontal cortex they allows you to exert self-control, decision making, judgment, and so on the one hand you have this enhanced drive to take the drug when they see a condition stimuli but on the other these areas of the brain and that shows up there, you can see images that monitor how much glucose the brain is consuming and when you have pathology, you see a decrease in glucose consumption, very, very senseive the indicator of brain patholog you see a or in moll person in the frontal cortex and you see the person that's addicted and you can see how eroded the activity of the brain is. so this area is metaphorically the break brakes of your bra. so it's like one thing... and that's what you hear from drug addicted people. they tell you i don't understand when i take the drug.

it's not pleasurable, i just caot control it. it's like driving, you want to stop without brakes you cannot stop. and this is at the essence of what we call free will. you want to be able to say i don't want to do this. i want to be able to not do it and most of the time succeed. >> rose: what is this teaching us about how to address addiction or treat addiction? >> well, first of all it's telling us these changes are lo lasng, unfortunately, and they persist months and sometimes years after a person stops taking the drug so it's a chronic disease which means that to start with a treatment of addiction will require sustainability. the notion you're going to go for rehabilitation for one month and then cured is not correct. it's magical thinking. addiction is lik hypertex or diabetes, you need treatment for a long period of time the

identification that addiction involves multiple circuits or networks. also identifies that you require a multiprong approach for its treatment. so can y strengthen self-control? can i do something as a therapiswith behavioral interventions with exercises of the brain or with medications to strengthen that frontal function? can i do something through behavioral intervention or medication to weaken the conditiong so when i see the stimuli i don't desire them? can i do something as an intervention to make that center that is no longer very active respond to natural stimuli so that the person gets motivated by things that are t just the drugs. so it's a multiapproach, multiprong approach and a rick in addition it's a chronic disease. >> rose: let me move to jeans and how they task neural paths.

>> the humane human brain is what we want to understand and human brain disorders. so the human brain is you what nek but the parts that make up the brn are not unique. the the brain is built from genes, they're about 25,000 genes that are use to make the brain and many brain disorders are at least in part genetic disorders. we want to understand those so that we can understand what the disorder is so we can think of way ways of intervening in the disorder based onhat basic knowledge of wt has gone wrong. so the trick to doing that is that human genes are shared with animals. almost all of them are present in other animals. it's and that's the trick that scientists use to try and translate back and forth

understanding biology diggs orders by using genetics and jeans to see what's happening in a normal brain and an abnormal brain. so one example is genes for sleep. so sleep is one of the important thing that the brain does for many hours everyday and sleep is a phenomenon that humans do and animals do. dogs sleep, mice sleep,lies sleep. and our understanding of the biology of sleep and the way the brain controls it comes first of all from studies of fli, from understanding their natural biological rit ims and why they were active in t day and less acve at night. and then we learned fly biology corresponded to the human biology as well so that explains whsome people are morning larks and some are night os. some of the same biology is involved. and sleep can also cause disorders, brain disorders that are slee disorders. one example... and it' a rare

disorder but fascinating. is called narcolepsy and cataplexy. and this is a disorder whe sleep starts to invade the waking state. so people know that narcoleptic people are drowsy. they'll suddenly fall asleep at inappropriate times. and, in fact, sometimes they'll just collapse because their body will relax the way your muscless relax when you're asleep. and sometimes they'll start hallucinating because they'll be dreaming while they're awake. so this is a very mysterious disorder. we had no idea what was going on withhis disorder until we started studying similar disorders in other animals and the person who did this is a man named emmanuel mineo who ran a sleep xwin i can and people said "my dog has this funny behavior." like this littleachshund, it's a cute dog, he's touching it on the head, holding the dog seems to be a happy dog and the dog is

just sort of sitting there like what happened to that dog? dog's not moving, dog's relaxed. dog just suddenly fell asleep for no reason. this is a narcoleptic dachshund. now, there's nothing wrong with this dog, it's not unhappy or in pain. gets up in a second, runs around again. t for just a moment it was asleep for no reason. and it had... because these dog had is unusual behavior... i should say no dogs were harmed in this study or in the making of that movie but in the dogs it was possible to track down the gene that was abnormal more clearly and to identify the brain ccuit that was abnormal and find what was happening. it turns out narcolepsy results from the lack of a brain chemical called hypoyes tin made from a part of the brain cled the hope them mus and it suppresses the sleep state during waking. and only by studying animals did

we learn something about human sleep and more than that we learned something about human consciousness that i find is amazing which is that there's a chemicalnvolved in separating out the parts of our brain action. the. >> rose: so understanding this, understanding these various aspects of the brain in relationship to dist disorder, how... what have we learned about sort of the developing brain amend and the mind? >> i'll give you several examples. everyone here will have their own favorite. we firsted learned about the circuits nora was talking about, the addiction circuit, by a series of studies by the scientists who stimulated this pathway and found what we called the reward circuit. so there is a bac circuit in the brain that gives you a sense of pleasure when you eat, when

you make love, when you look at a painting you love, when you look at a person that you love. this system becomes active. so what you see in addiction in the early phases is recruitment of a basic circuit involved in pleasure. so we learn a lot about normal functioning of th brain by seeing its disturbance in disease states. >> add to that in terms of where... i mean, the sense of people understanding the specifics about the biological basis of understanding the brain and where this will take us in terms of understanding the whole range of things that open new frontiers to us. >> well, i think gerry made a critical comment in passg and i want to go back to that because it really fits into this charlie. the idea was that when you lk at these neurodegenerative disorders, what you see in terms of thinking and behavior is a very elite manifestation and for

mental illnesss that's a critical, transformative idea. if reall psychosis is a very late stage of schizophrenia we have been locked into all of our diagnostics by sing let's look at abnormal behavior and thinking and that' how you fine them, you're already getting the very late in the cycle. so if you can begin to think about these as brain illnesses and you can begin to identify something much earlier the way we're trying to do with parkinson's and now with schizophrenia and autism where we can move the cycle forward the same way we do for heart disease. we don't wait for someone to have a heart attack to make a diagnosis of ischemic heart disease. this is a transformative idea because it does point us towards trying to make early detection, early intervention. and-the-preplgs, or prevention of the disability much more likely. it changes the discussion. >> a loft of the work that has come out of tom's institution has shown that most o these

disorders are, in fact, developmental disorders. >> if you look at the epidemiologists, for adults with psychiatric disorders, 50% describe onset by age 14. 75% age 25. so these are really, as nora said, these are chronic diseases of young people. >> this is why it's so devastating. >> rose: because they start early rand so pervasive. >> i wanted to come back to your origin gnat question. i agree with everything tom just said but you asked how our brain disorders informed us about the human mind and the areas that eric knows really very well are surgeries on patients who ha epilepsy, for example removing the part of a brain in a patient named h.m.. this patient had what's called status epileptic, could not stop seizing, so surgery was life saving in that case. and what happened was they removed the tips of the region

of the brain called the temporal lobe. and that opened up the study of memory and the hippo cam us the in not just disease states but how we remember things and how that ithe glue for our personality and our conscious so each one of the... and i think we can all name many examples where a treatment of a disease or analysis of the disease has been influential in teaching us about the normal brap. ani quite agree that.. >> rose: all the things we talked about in the first series, whether it's perception or motion or emotion or creativity or memory. >> yes. >> rose: all of that. >> yes. >> rose: and we... >> one of the things that we've also learned, not just from diseases neurological or psychiatric but just studying e normal brain with imaging technologies, for example, you're saying well, how is it pushing our understanding?

now we recognize that the brain is a complex set of networks and that there are certain areas of the brain that act like cops and any one given area can participate in more than one network and that these networks have changing dynamically. i think if you want to get a metaphor that could approximate that is really the one of an orchestra because you have the different instruments that could be different areas of the brain but each instrument can sound completely different on the basis of how it's coordinated with the others and, of course, of the part. and so that's exactly how we have to look at the brain is not this static area that we can identify. if it's true, the broca and wernicke e crucial hubs for networks of language. but you can get language disorders if you have damage outside in areas that are part of that network. even though they are not physically located in wernicke and broca. so that understanding of the

network architecture of the brain is something that has changed dramatically. brain of children and adolescents is different than the brain of adults. not better, just different. one of the ones that is more fundamental is the connectivity. the brain of the adult is much more cnected than the brain of an adolescent. that doesn't mean it works worse works differently. so for example a dhaex is not fully formed, your differental cortex with your limbic brain and that connection that allows me to literally control the activity of the amygdala is not fully formed until you are in your 20s. that explains why adolescents are much more sbelsive, why they're much greater risk takers why they're intensity is much greater. because they don't have that cognitive control that allows you model late reactions. >> rose: i'm not sure that's a

good thing. i'd like to go back to being an adolescent. >> everything has a plus and minus. >> i'd like to pick up a little bit on on of the ideas that emerges from nora's idea about networks which is that if you thk of a brain as a series of fixed areas, which one of which does one thing, well then if you have damage or a problem you're stuck. it's over. if you think of a brain as a network of interconnected areas, very often you can think about doing work arounds and... >> compensations. >> compensating. and the brain is incredibly flexible and for everything we know about it it has the ability to find a work around for some sort of pre-existing problem. and this happens at large brain areas and microscopic levels. >>uickly in some case. >> yes. there's a common form of human mental retardation called fragile x syndrome that affects something like one out of 3,000 boys. and this results in a... from a defect in a particular gene that acts as a supervisor of other

gene's aivity during learning process in the hippocampus. but there are other supervisors of learning processes and sometimes you can target drugs to those other areas and bypass the defect and in animal models that's successful at reversing their learning defects. so the more we think about the brain as a set of networks, a set of interconnected functions where there might be one way or working at one time and a different way of working at another the more we can think about sensible ways of intervening in disorders. maybe we can't cure the underlying gene, maybe we can't fix a lesion but maybe we can do a work around that will improve people's lives. >> this is exactly what deep brain stimulation has done in parkinson' disease. you don't stop the degenerative process but by stimulate ago compensatory area of the brain you can really reverse the moment. >> rose: that's what you meant by early deit is there is something you can do >> and it's speaks to corey's

point about flexibility in the brain which i seem to be a very hopeful sign. there are children are long standing autism, very severely affected. will not speak to their parents, ll not look to their eye. but it's come to light tt in aa high fraction of children, maybe 25%-- at least that's what what their parents tell uss that a low grade fever seems to reverse some of the signs and symptoms of autism. snoond and why is that? >> we don't know. but i can tell you there's a huge effort to understand it. what is it about the network naungs is not correcting the original deficit but can somehow compensate? but the reports from parents are quite dramatic. "my child told me he was hungry. hasn't spoken directly to me in months" or "has looked me the eye" or "has embraced me."

these are n minor changes and if we could understand the network changes that accompany there that, whether it's inflammatory responseor a direct effect of the temperature itself we would learn alot. >> rose: is it too large a statement to say, eric, that we have learned more about the brai from studying disorder than any other process in >> wve learned a lot. we've learned from other techniques as well. we've learned a lot from aging. it's fantastic. >> rose: because the imaging is often of disorder, too. >> true, you're absolutely right. we've learned from multiple sources, we learned an enormous amount. in the early days most of what we learned was from brain sorders. now we have ways of studying normal function with imaging and animal models altering genes that have taught us a great deal. so it's multiple sources that i would say learning from disease states, imaging and genetics.

>> rose: one of the things i've learned from this working on the last episode, the last series and working on beginning to think about this series is that these extraordinary things about the brain, i used to think that seeing and perception was about your eyes and not necessarily about your brain. all these basic things that i had to learn and that motion was about your muscles and all that kind of stuff. dr. kandel has helped me understand this. what have we learned as we've learned about so many differen things here, what have we learned about intel sxwlens is there anything about disorder that's taught us about the process of... and can we define what intelligence means? it's difficult bauds it's not a single quantity. it's... people's intelligence n vary tremendously. having a good memory a component of that being very creative. buck quite creative. take chuck close, for example,

he's dyslexic so he has difficulty with adding and some tiftty wh reading but he's amazingly creative. there's a fraction of people with awe. they are very creative even though they have a severe language deficit? many cases. so there are multiple things, multiple intelligences. >> i'd like to say something on this point, actually. which is that this is a really good example of a problem or a process where there are complex genetic interactions that are also interacting with environmental factors. and human intelligence is absolutely a combination of the heart of... the hand of cards that you were dealt at birth but also everything that happens around you starting in the womb with how good your prenatal environment is. everything that happens in your life after that, your socioeconomic status, everything we know about education of early children, their acquisition of language and so forth. there are dramatic studies that

show... very often you will hear people say "intelligence is half genes and half environment." that's a description of a kind of study that's done on middle-class children in good environments. if you do the same udy on children in bad socioeconomic environments you find it's 10% genes and 90% environment. so if you have a lot of gin net i can pen potential, yo can make good at that wherever you are. but environmt is at least as important in controlling different kinds of ctors. >> rose: both positively and negatively. >> positively and negatively. so these things never act alone. there's always an interconnection between genetic factors and environmental factors and a complex human process like intelligence. >> rose: we're just beginning to understand the complexity of the brain. where are we trying to get? where do we want to be halfway to? >> make i can use the genome as

the great example or metaphor for this. a decade ago we wer trying to get the sequence of the genome and we thought once we had that sequence we wouldunderstand human biology. (laughter) well, we understood some things. the book of life. it was helpful in some ways. it helps us to know as corey said that there's 25,000 genes. we thought there would be 100 wasn't that different from the mouse or wornl or other species. what we didn't snow what makes ch of us special and we're learning a lot about the extraordinary amount of variation in each of our genomes you betr believe the brain is more complicated than the linear sequence of genetic code. a lot more complicated and we're just beginning to understand what is the range of variation? whatakes each bra special and how does it develop? how does it wire it? how do genes and environment altar that process.

we're at the 2% level for this. we have more to learn. >> i agree with several things that have been said by nora. when we talk about the brain what we're really talking about is the great unknown in between charlie you said you knew about eyes and movement, we know about the inputs and outputs, we know a lot about now nerve cells wo. what we don't understand is how these things are associated into process. and i love the phrase "social cognition" and "social brain." after all what i would like to know is how we interact with one another. what is it? what neural mechanisms regulate empathy, understanding. preference. where you know what i'm thinking you know if i'm happy, upset, sad. this is a secret to our society

and i do agree this is going to be some very complex combination of genes and environment. corey gave an example of where one gene caused the dog to go to sleep but also very eloquently stated that there are going to be complexes of genes, mae thre or four hundd regulating a simple behavior. and the distinction between environment and genetics tends to blur because these genes may enhance the probability of some phenomenon or some disorder but not cause it. may enhance the risk to environmental factors. it's going to take all of the tools we have to understand that. >> rose: i'm fascinating by intuition and what it is. where does it come from and all that kind of thing? it's clearly part of... >> absolutely. >> rose: i'm waiting for you to say to me that's a stupid question. (laughs) >> no, no. >> there are great brain

studies... >> there's no stupid questions but lots of stupid answers. >> there are brain studies of teaching individual sort of card games that shows their subconscious brain, their subcortical brain understands the rule before their conscious brain can explain the rules. >> rose: i just interviewed the biographer of steve jobs and he talked about steve jobs went to india and came back with a great sense of respect for intuition. one of the things that let. >> he also wrote a biography of albert einstein and he talked about albert einstein's moment of intuition when he said, well, maybe there's nothing such thing as sing chronny in time. what a leap of imagination that was. explain the time and space continuity. he was walking down the road with a friend of his and he had this intuition that changed everything in terms of our perception of the universe.

>> the idea that you could now begin to study the mind through the brain, right? that's what we're about. and it's a question of putting together what are the right constructs? what are these mental functions that are worth trying to get at. >>uestions to ask and how to get at that. >> one interesting thing which we talked about earlier which go to corey's int about interaction with the environment is there was an article a couple of days ago in the "new york times" on a woman who has schizophrenia and who solves her disee by having a gh level executive job. so this is a person who a hundred years ago wouldrobably in a psychiatric hospital. but because of t fact that she was in an environment and motivateed to to do this forced thoers go to work even though she has problems. periodically takes te out. we saw ellen sachs, the same kind of thing. so it depends on environmental factors allowing you to li with your lness and help you

along rather than giving into it. >> rose: at the end of this series we hope well have learned the kind of things we just talked about. what are we going to try to learn in our next episode. >> in the next episode we're taking up the moist complicated problem that we confront in brine science, the nature of consciousness. there's a beginning, very preliminary understanding of how aspects of consciousness work. and one of the things that came out of that is that what corey referred to, the power of unconscious mental processes. that there is a lot of mental activity. a better made without thinking about in the detail, just going for it. so we'll see the difference between conscious and unconscious mental processes. we'll also consider dorders of consciousness. >> i look forward to seeing it.

thank you very much for coming. captioning sponsored by rose communications captioned by media access group at wgbh access.wgbh.org