>> 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 considering psychiatric, addictive and neurological disorder which is encompasses all brain disorders. 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 occur within psychiatry given in good part by basic science. there was a sort of 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 discuss in the earlier series, fundamental assumption of the new science of mind is that every mental process, the most trivial ones-- hitting the golf ball-- to the most sophisticated creative act are all mediated by the brain and psychiatrists began to realize that all mental disorders air, detectiveive disorders, must be brain mediated. >> rose: episode one of the carly rose brain series two underwritten by the symons foundation coming up.

captioning sponsored 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 atom was to the 20th century. we continue our exploration 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 provide a parallel view of brain disorders. for each program and disorder scientists and researchers who study the disease from a medical and scientific perspective will join us. we will discuss certain disorders with patients. some are physicians who speak about their illnesses medically and privately. finally we'll understand our understanding of the human mind. in tonight's episode of our second sere rose we discuss how neurological psychiatric and addictive disorders result from disturbances in neural systems.

our understanding has evolved greatly throughout history. two centuries ago mental illness was believed to be a disease of the mind not the brain. those suffering 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 torture. as time 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 has 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 me to discuss where we are now and where we're going are a remarkable group of scientists. gerald fischbach is a professor at columbia university and a

director of the simons foundation autism project. thomas insel, director of the national institute of mental health at the n.i.h.. nora volokow, director of the national institute of drug abuse at the n.i.h. and cornelia bargmann, a professor at rockefeller university. once again, my co-host is dr. eric kandel. as you know, he is a nobel laureate, a professor at columbia university and the howard hughes medical investigator. we begin our program with the question: what are the similarities and differences of various brain disorders? >> we're going to consider various brain disorders and, as you know, 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 considering psychiatric, addictive and neurological disorder which is encompasses all brain disorders. we're going to ask the question what are the similarities and differences between them? now, this is an issue that has been discussed for decades and

the thinking about it can be divided into sort of three phases. the first phase, which is perhaps best called the moral phase 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 addictive and psychiatric diseases were isolated from the rest of the community, put into asylums, put in chains, and often treated very, very harshly. needless to say, not only was this inhumane but it was counterproductive. then the situation changed when a great french physician in the 1800s, came along and he changed things dramatically. he asserted very strongly that

psychiatric diseases and addictive diseases are medical disorders. they're not weaknesses of character. and that they need to be treated in a humane fashion. he removed the chains of people in the great paris psychiatric hospital and he began to get patients to talk to him about their problems and to 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 say these diseases are likely to occur in people who have a genetic predisposition who are put under social or personal stress. this had an amazing impact in the field the next phase, which began around 1860 began with a guy called pierre paul broca. >> rose: this is the anatomical

phase? >> exactly. you know this stuff better than i do, for god's sakes. we should change positions. (laughs) >> rose: i'm a good student. >> 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 who had a specific form of language disorder. they could understand language perfectly well but couldn't express themselves in language and when they died and came to autopsy found that invariably the left side of the brain and the front of the brain was a lesion. about 15 years later, carl wernicke, a injure manureologist picked up the study of aphagia and he found the 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 also on the left side and the lesion was at the back of the brain. moreover, he realized that the lesion of his patient and broca's patient, those two areas now called wernicke's area and broca's area, are interconnected. that made him realize that complex neurological disorders are not due to a lesion at one site but a lesion at a number of sights that are interconnected. people now began to explore a number of neurological diseases and jerry fischbach is going to speak about that and saw that all of them could be localized to one or more areas of the brain, neural circuitry of the brain. when psychiatrists began to explore the brain or psychiatric disorders, schizophrenia, depression, addiction, they didn't find obvious lesions in the brain. and so many thought that these are not brain-based disorders, these are mental disorders.

and a few far-sighted psychiatrists realized early that it's very likely that they are brain disorders but undetectable with the techniques available. the situation changed remarkably in the last 40 years. a new synthesis occurred within psychiatry giveen in good part by basic science. first of all, that was sort of 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 sophisticateive elaborateive creative act-- are mediated by the brain. and psychiatrists began to realize that all mental disorders, addictive disorders, must be brain mediated. this was further advanced by two other major advances in the field.

one was beginning with franz coleman around 1950, people began to realize that all of these disorders have a genetic basis and that strengthened the biological underpinnings of it. finally imaging techniques became 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 do development contribute? what does environmental factors contribute? and corey who pioneered genes is show us how we can approach that. so we're in for a terrific discussion. >> rose: let me begin with gerry fischbach. tell me about this notion of neurological disorders and the neural systems they involved. >> i want to begin by talking 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 phenomenon that we know in the universe. it's made up of over 100 billion cells and every one of these cells is working hard. they need to generate enormous energy to maintain their signaling, 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 the 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 find 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 anymore. the phenomenon of stroke, when the blood supply is reduced, can be demonstrated if you think of the first slide, there are blood vessels that arise in the... near the origin of the heart and thats a send 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. but it receives about 20% of the outflow of the heart. it shows you how critical the energy needs are. and 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 a 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. on the left is broca's area there mentioned and the right is wernicke's area. if you look closely you can see they're really supplied by different branches of the artery. so it's possible to close off blood flow to one area and have a broca syndrome and express aphagia or close off blood flow to the posterior, wernicke's area, and have a receptive aphagia, not understanding the words spoken. so stroke is a huge problem. on a more chronic basis, 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 and the brain stem called

the substantia nigra and it's a group of cells that make the neurotransmitter dopamine. these cells begin to degenerate long before-- years before-- there are 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.h. 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 the clot 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 has developed for recovery of function. but what you have asked about is this very early critical period. it's why one must be acutely aware of the early signs of a stroke. don't go to bed if you think

there's something going on that... >> rose: 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 side of the face. weakness of one arm. notoriously if you remember that diagram of 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 this damage for the stroke minimized because of this early intervention. >> rose: okay. let me move to tom and talk about disorders in the context of what you look at. >> so we talk about mental disorders as brain disorders as well. and here we've got a chrebs of really a few of the mood and anxiety disorders. depression, p.t.s.d., maybe

obsessive-compulsive disorder. >> rose: p.t.s.d. is... >> post-traumatic stress disorder. psychotic disorders like schizophrenia. sometimes mania, bipolar disorder fits into that category. we've got eating disorders like anorexia. then there are disorders of childhood, whether it's autism or attention deficit 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 the way gerry's been talking about them because these are disorders that don't have a focal legion. when you look at the brain here you don't find an area of dead cells. >> rose: you can't do an autopsy and find... >> there's nothing there. people have looked for years but in each one of these cases what you find is there's nothing there on autopsy. yet when you use brain scans the way we can now, as eric mentioned, we've got this enormous powerhouse of tools to be able to look at the brain and how it functions in health and

disease and we can see that there are circuits that aren't functioning right. so each of these disorders involves some part of the circuitry that's either hyperactive or inactive or the communications. we don't know, actually, whether there's because there are lesions that are microscopic that you can't see, maybe change at the synapses that are critical. maybe the wiring is off or maybe there's just a rhythm problem. or maybe all three are happening at various times. but the modern view of this is that what we've got here are problems with the circuit. we should take a look at depression, because may be the best example. depression, as you know, is very common. in any given year, some 6% of people will be incapacitated by depression. it's that ears you 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. the 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 in this image. and this is an area that sits deep in the frontal lobe. it 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 of 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 node in that circuit. the rest of the prefrontal cortex which is important for decision making and judgment and planning for the future is also involved. as is the variety of areas that are connected. the amygdala which we think of as the hub of emotion, the horse shaped area called hippocampus which is critical for memory and an area called the insula, which is an area that's very important for bodily somatic sensations

and it may be the reason why people with depression feel they're dead inside. there's no vitality. there's nothing there. the hypothalamus is another area involved and there's probably the reason why there's this loss of drive, whether it's sex drive or appetite in people with depression. all of these together form a simple circuit. there are probably many other areas that are involved but these are the areas that seem to show up over and over again and they're areas that are important because the treatments we have-- whether whether there's psychotherapies or medications-- probably hit different parts of the circuitry and, amazingly in the last few years it's become clear that if you go in and actually change the firing rate of area 25 itself, that that by itself can treat depression in people who haven't been helped by medication or psychotherapy. >> rose: how do you do that? >> you use a deep brain stimulation technique. a tool that was borrowed from the world of parkinson's where

we also have that as a treatment for parkinson's. in this case you go into this one area that looks like it's overactive. by stimulating near it, you reduce the firing rate. it reduces activity and people will respond accordingly with a reduction in depressive symptoms and some with a true remission of the disorder. so this is a very powerful demonstration that this disorder can be thought of as a circuitry problem. almost like an arrhythmia where, by changing the circuit, changing the it are. you can get improvement. >> there are two other things that emerged from the thing that tom is talking about. this is helen mayberg's work. she introduced us to deep brain stimulation. she also showed that in milder forms of deflaegs do respond to therapy, she imaged the circuit and she saw there was reversal in the abnormality. so she could tell that psychotherapy produces functional changes in the brain. it's really quite beautiful.

and in that case showed very similar changes to selective serotonin uptake inhibitors. >> and it begins to tease this apart. her idea-- and i think it's one people are getting interested in-- is that depression is not one disorder. it's many different disorders that may share some common symptoms but different parts of this circuit could be more or less active in different people and that may indicate who's going to respond to which treatments. that's a question that we're very actively investigating at this point. >> me turn to nora and talk about addiction. >> addiction, just like tom was mentioning for other mental illness is one of the mental disorders and it's circuits. and in the past we believe that drug addiction was a result of... eric was saying of poor moral character. and what has been fascinating as we start to understand what are the changes in the brain that occur on people in are addicted is that that has given us enormous insight about what it

entails to hve free will and to be able to exert control over your decisions. because addiction at the fundamental level is the loss of the capacity to decide what you want to do and be able to carry it through. and over the past 15 years i would say we've done enormous advances in understanding drug addiction and the effects of drugs in the human brain and in animal models and we now know, for example, all of the drugs-- whether it's legal or illegal, biology doesn't make distinctions-- have a common characteristic which is they increase the concentration of the chemical dopamine in areas of the brain involved with motivation and reward. and this is the mechanism that nature created to ensure that you will do behaviors that will enable you as an individual and as a species to survive. so by creating the sensation of pleasure which is transmitted by release of dopamine, not only do you have that experience but unbeknownst to you you get condition. and what is conditioning? a deep memory in emotional parts

of the brain that will recognize that stimulus. the next time that you see it, it will generate the drive and motivation to pursue it. and you can see how extremely clever nature is. because that way if you ate a 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 hijack that system, but they do it as a much more potent way than any of the physiological norm and so as a result of that it's not just the pleasure that you are generating by liberating dopamine, but the conditioning. and now with imaging, for example, we can directly go inside the brain of people and see what is happening to the brain and start to understand why their behavior gets so disrupted and the first slide shows how we do it. it's quite simple. you use brain imaging, this is a radioactive substance that concentrates in the center parts

of the brain which are in red there. that's where you have the areas of the brain with reward and motivation. to the left is an individual not taking a drug and to the right you see the individual taking a drug like cocaine which increases dopamine, then dopamine floods the brain and removes the activity. so this is understood right now is the reason why drugs can produce addiction. and for many years, in fact, it has been believed until very recently that people who are addicted to drugs because they were just more sensitive to the rewarding effects of them, they're more pleasurable, there was more dopamine released. however, when you apply these tools to actually 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 a normal control, normal controls, images, in the left with no drugs, in the right with drugs and you see the red is going down because dopamine has gone up and has pushed the activity away.

the lower panel shows people that are addicted to cocaine and you can barely see any difference when they are with or without drugs. and that is because in an addictive person-- contrary to the belief-- the drugs no longer can produce large changes in dopamine. so then, well, how do you then make sense of something like that? and that is at the essence and the fundamental understanding of addiction. you have transferred the value of the drug into the stimuli that surrounds the drug. that's what we call the conditioning. so in this image you see no effect of the drug in a person that's addicted. but if you subject them to cues, seeing a person that they've taken drugs with, seeing the paraphernalia of the drug, take a $10 bill with which they may have snorted and that's the next image. when you expose individuals 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

video that is full of 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 charging 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 drugs, they go back to the environment but their brain is wired like this to release dopamine the moment they see a stimulus, a person with which whom they are taken the drug and that elicits the enormous desire to take the drug and that's why they relapse. and at the same time, in parallel to this shifting in the hypersensitive toy the condition stimuli we now know that repeated administration of drugs damages the areas of the brain that tom was speaking about, the frontal cortex, that 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 conditioned stimuli but on the other these areas of the brain-- and that shows up there, you can see the images that monitor how much glucose the brain is consuming-- and when you have pathology you see a decrease in glucose consumption. very, very sensitive indicator of brain pathology. you see a normal person in the frontal cortex, this area here on the upper part and you see the person that's addicted and you can see how eroded the activity of that area of the brain is. so this area is metaphorically the brakes of your brain. 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 cannot control it." it's like driving, you want to stop, without brakes you cannot stop. and this is exactly at the essence of what we call, of course, free will. because you want to be able to say "i'm not going to be... i

don't want to do this." and you want to be able not to do it. and most of the time succeed. >> rose: so what is this teaching us about how to address addiction or treat addiction? >> well, first of all, it's telling us these changes are long lasting, 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 that you're going to go for rehabilitation for one month and you're going to be cured unfortunately is not correct. it's magical thinking. addiction is like hypertension or diabetes. you need treatment for a long period of time. the identification that addiction is not just one region of the brain but it involves multiple circuits or networks. also identify that you require a multiprong approach for its treatment. so can you strengthen self-control? can i do something as a

therapist with behavioral interventions, with exercises of the brain or with medications to strengthen that frontal function? can i do something to, again, behavioral intervention or medication to weaken that conditioning? so that when i see that stimuli i don't desire them. can i do something as an intervention to make that reward center that is no longer very active respond to natural stimuli so that the person gets motivated by things that are not just the drugs. so it's a multiple approach, multipronged approach and the recognition that it is a chronic disease. >> rose: corey let me move to genes and how they affect the neural paths. >> the human brain is what we really want to understand and in this context human brain disorders and the human brain is unique but the parts that make up the brain are not unique. so the brain is built from genes. they provide the parts for the

brain and the instructions for using them. there are about 25,000 genes used 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. and also so that we can think of ways of intervening in the disorder based on really that basic knowledge of what has gone wrong. so the trick to doing that is that human genes are shared with animals. of the 25,000 human genes, almost all of them are present in other animals. and often it's much easier to figure out what a gene is doing by studying that gene is n an animal than by studying that gene in a human. and that's the trick that scientists use to try and translate back and forth. understanding the biology of brain disorders by comparing humans to animals, by using the genetics and by using genes 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 really important things that the brain

does for many hours everyday and sleep a phenomenon that humans do and animals do. dogs sleep, mice sleep, flies sleep. and our understanding of the basic biology of sleep and the way that the brain controls it comes first of all from studies of flies, from understanding their natural biological rhythms and why they were active in the day and less active at night and then we learn that the fly biology corresponded to the human biology as well. so some of that explains why some people are morning larks and some people are night owls. some of that same biology is involved. and sleep can also cause disorders. there are brain disorders that are sleep disorders. and one example-- and it's actually a very rare disorder but a fascinating one-- is called narcolepsy and cataplexy. this is a disorder where sleep starts to invade the waking state. so people know that narc narcoleptic people are drowsy, they'll fall asleep at

inappropriate times and, in fact sometimes they'll just collapse out of nowhere because their body will relax the way your muscles 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 with this disorder until we started studying similar disorders in other animals. and the person who did this, if we turn on the video, is a man named emmanuel mineo at stanford university who ran a sleep clinic and people started coming to him and saying "my dog has this funny behavior." like this little talk sand here, that's emmanuel playing with the talk sond, he's touching it on the head, he's holding the dog, he's a happy dog and the dog is just sitting there. what happened to that dog? the dog isn't moving. the dog just suddenly fell asleep for no reason. this is a narcoleptic dachshund. there's nothing wrong with this

dog. it's not unhappy and in pain. gets up in a second, runs around again but for just a moment it was asleep for no reason. and it had... because these dogs had this 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 circuit that was abnormal and to find what was happening. it turns out that narcolepsy results from the lack of a brain chemical called hypoyes tin made in a part deep in the brain called the hypothalamus and that brain chemical spreads through the brain while you're awake and it keeps you awake from dreaming and suppresses the sleep state during waking. and only by studying animals did we learn something about human sleep. more than that, we learned something about human consciousness that i find is amazing which is that there's a chemical involved in separating out these different parts of our brain action, the conscious waking part of our brain from the unconscious sleeping part of

our brain. >> rose: so let me open up this up to a wider discussion and this is a very much of a naive question. so understanding this, understanding these various aspects of the brain and relationship to disorder, how... what have we learned about sort of the developing brain and what we call the mind? >> i'll give you several examples. everyone here will have their own favorite. we first learned about the circuits that nora was talking about, the addiction circuit by a series of studies by olds and meler in who stimulated this pathway and found what we call the reward circuit. so there's a basic circuit in the brain that gives you a sense of pleasure when you eat, when you make love, when you look at a painting that you love, when you look at a person that you love. this system becomes active. so what what you see in addiction in the early phases is recruitment, parasitism of a

basic circuit involved in pleasure. so we learn a lot about normal functioning of the brain by seeing in the disease states. >> rose: after 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 really critical comment in passing and i want to go back to that because it really fits into this, charlie. the idea was that when you look at these neurodegenerative disorders what you see in terms of thinking and behavior is a very late manifestation. for mental illnesses, that's a critical, transformative idea. if really psychosis is a very late stage of schizophrenia and we have been locked into all of our diagnostics by saying let's look at abnormal behavior,

abnormal thinking and that's how you define them, you're already getting there 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 in parkinson's and now in schizophrenia, even in autism where we can move the cycle forward the same way we do for heart disease all the time, 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 preseplgs or prevention of the disability much more likely. it really changes the discussion. >> in fact, a lot of the work that has come out of tom's institute has shown most of these disorders are, in fact, developmental disorders. >> if you look at the epidemiology with adults with psychiatric disorders 50% describe onset by age 14, 75% by age 25. so these are really... as nora

said, these are chronic diseases. these are chronic diseases of young people. >> this is why they're so devastating. >> rose: because they start early and are pervasive. yes? >> i wanted to come back to your original question. i agree with everything tom just said but you asked how have brain disorders informed us about the human mind and the areas that eric knows really very well are surgeries on patients who had epilepsy, for example. removing the part of a brain in a patient named h.n. this patient had what's called status epileptic, could not stop seizing so surgery was life saving. 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 hippocampus in not just disease states but in how we remember things and how that is the glue

for our personality about our consciousness. so each one of the... and i think we all can name many examples where a treatment of a disease or analysis of the disease has been influential in teaching us about the normal brain. and i quite agree that... >> rose: all those things that 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... >> and i was... one of the things that we've also learned, not just from diseases neurological or psychiatric but just studying the 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 are like cops and that any one given area can participate in more than one network and that these networks

are changing dynamically. i think if you want to get a metaphor that could approximate that, it's really the one of an orchestra. because you have the different instruments that could be different areas of the brain, right? but each instrument can sound completely different on the basis of how it's coordinated with the others. and so that's exactly how we have to look at the brain. it's not this static area that we can identify. if it's true, broca and wernicke are crucial hubs for network 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 really has changed quite dramatically from the way that we used to look at hit in the past. brain of children and adolescents are very different from the brain of adults. it's not that one is better than others.

there are many differences but one of the ones that i think is more fundamental is the connectivity. the brain of the adult is much more connected than the brain of an adolescent and so... that doesn't mean it works worse. it works differently. so for example a connection that is not fully formed is your frontal cortex, your olympic brain. that connection athat allows me to literally control the activity of the amygdala, the limbic brain, is not fully formed until you're 20. that explains why adolescents are much more sbelsive, why they're much greater risk takers why their intensity is much greater overall. because they don't have that cognitive control that allows you to model late reactions. >> rose: i'm not sure that's good thing. i'd like to be an adolescent. >> everything has a plus and a minus. >> i'd like to pick up a little bit on one of the ideas that emerges from nora's idea about networks which is that if you think of a brain as a series of

fixed areas, each one of which does one thing, well, then if you have damage or a problem you're stuck, it's all over. if you think of a brain as a network of interconnected areas then very often you can think about doing work-arounds. >> compensations. >> you can think about compensating and the brain is incredibly flexible. for everything we know about it, it has the ability often to find some kind of a work-around for some sort of a pre-existing problem. and this is... this happens at large-brain area levels, it happens at microscopic levels. 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 sort of a supervisor of other gene activity during learning processes in the hippocampus. but there are other supervisors of learning processes. and sometimes you can target drugs to those other areas and try to 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 of 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 really improve people's lives. >> this is exactly what deep brain stimulation has done in parkinson's disease. we don't stop the degenerative process, but by stimulating a compensatory area of the brain you can really reverse the movement. >> rose: that's what you meant earlier by early detection. there is something you can do with early detection. >> it also speaks to corey's point about flexibility on the brain which i find to be extremely hopeful sign. there are children with long-standing autism. very severely affected, will not speak to their parents. will not look them in the eye. but it's come to light that in a

high fraction of children-- maybe 25%, at least that's what their parents tell us-- that a low-grade fever seems to reverse some of the signs and symptoms of autism. >> rose: and why is that? >> we don't know. but i can tell you there's a huge effort to try and understand it. what is it about the network function that it's 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 weeks and months. or has looked me in the eye or has embraced me." so these are not minor changes. and if we can understand the network changes that accompany that, whether it's an inflammatory response or a direct effect of the temperature itself we would learn a lot. >> rose: is it too large a statement to say, eric, that we

have learned more about the brain from studying disorder than any other process? >> we've learned a lot. we've learned from other techniques as well. we've learned a lot from imaging. it's really fantastic. >> rose: but the imaging is often of disorder, too. >> true, you're absolutely right. you're absolutely right. we've learned from multiple sources. we learned enormous amount. most of what we learned in the early days was brain disorders. now we have ways of studying normal function with imaging and also in animal models altering genes that has taught us a great deal. so it's multiple sources. i would say learning from disease states, learning from imaging and genetics. >> rose: one of the things i've learned from this, working on the last episode, the last series and working on the beginning to think about this series is that these extraordinary things that the brain... i used to think about that seeing and perception was about your eyes and not

necessarily about your brain. all those basic things that i had to learn, you know? and that motion was about your muscles and all that kind of stuff. and dr. kandel has helped me understand this. but i still don't understand. and what have we learned... as we've learned about so many different things here, what have we learned about intelligence? is there anything about disorder that's taught us about the process of... and can we define what intelligence means? >> it's difficult to define it because it's not a single quantity. people's intelligence can vary tremendously. having a very good memory a component of that. being very creative. you can be quite creative and not be... take chuck close, for example. he's dislex i can so he has difficulty with adding and he has some difficulty with reading but he's amazingly creative. people with autism, there's a fraction of people with autism that are very creative, even though they have a severe language deficit in many cases.

so there are multiple things, there are multiple intelligences. >> i'd like to say something on this point, actually, which is that this is a really good example of a problem where 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 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, of their acquisition of language and so forth. there are dramatic studies that show... very often you will hear people say well, intelligence it's half genes and half environment. and that's a description of a kind of study that's done on middle-class children in good environments. if you do the same study on

children in bad socioeconomic environments you find that it's 10% genes and 90% environment. okay? so if you have a lot of genetic potential you can make good of that wherever you are. but environment is at least as important in controlling different kinds of factors like intelligence. >> rose: both positively and negatively. >> both positively and negatively. absolutely. >> so these things never act alone. there's always an interconnection between genetic factors and environmental factors in 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? >> maybe you can use the genome as a great example or metaphor for this. a decade ago we were trying to get the sequence of the genome and we thought once we had that sequence we would understand human biology. well, we understood some things.

the book of life. and it was help informal some ways. i mean, it helped us to know, as corey said, that there were 25 genes. we thought there would be 100,000. it wasn't that different from the mouse or worm in lots of other species. what we didn't know from that was what makes each of us special. and that we're learning. we're actually learning a lot about the extraordinary amount of variation in each of our genomes. now, you better believe that the brain is a lot more complicated than that linear sequence of genetic code. a lot more complicated. and we're just beginning to understand what is the range of variation? what makes each brain special and how does it develop? how does it wire and how do genes and environment alter that process? we're at the 2% level for this. we've got a lot more to learn. >> i absolutely agree with tom and with several things that have been set 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 we knew about movement. we know about the inputs and the outputs. we know a lot about how nerve cells work. what we don't understand is how these things are associated into persons. 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. i mean, this is a secret to our society and i do aagree this is going to be a complex correlation of genes and environment. corey gave an example of where one gene caused a dog to go to sleep but very eloquently stated

that there are going to be complexes of genes, maybe 300 or 400 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. and the environmental... and may enhance the risk to environmental factors and it's going to take all of the tools we have to understand that. >> rose: i'm fascinated by intuition and what it is. where does it come from and all that kind of thing. it's clearly part of... >> rose: absolutely. i'm waiting for you to say to me that's a stupid question. (laughs) >> no, no. there are great brain studies. >> there are no stupid questions but lots of stupid answers. >> there are brain studies of teaching individuals card games that shows that their subconscious brain, their subcortical brain understands the rules before their conscious

brain can explain the rules. intuition. >> rose: i just interviewed the biographer of steve jobs, walter isaacson and he talked about steve jobs went to india and came back with a great sense of respect for intuition. it was one of the things that happened to him. >> walter isaacson also wrote a biography of albert einstein. >> rose: i know, indeed. >> and he talked about einstein moment of intuition when he said "maybe there's no such thing as synchrony in time." what a leap of imagination that was to 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. >> it's the idea that you can now begin to study the mind through the brain. 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.

>> the questions to ask and how to get at that. >> one interesting thing we talked about earlier which goes to corey's point 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 disease by having a high level executive job. so this is a person who a hundred years ago would probably be in a psychiatric hospital but because of the fact that she was in an environment and was motivate to do this, forced herself to go to work even though she has these problems, periodically takes time out. we saw ellen sacks, the same kind of thing. so the environmental factors, allowing you to live with your illness and help you along rather than giving in to it. >> rose: at tend of this series we hope we will have learned some of the things we just talked about, the complexity and how it affects our understanding. what are we going to try to learn in our next episode?

>> in the next episode we're taking up the most complicated problem that we confront in brain 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 what corey referred to. the power of unconscious mental processes that on many levels freud was right that there is a lot of mental activity we're unaware of. certain kinds of decisions are better made without thinking about in the detail. just going for it. so we're going to see the difference between conscious and unconscious mental processes and we're going to consider disorders of consciousness, minimally conscious states. >> rose: i look forward to it. thank you very much for coming. captioning sponsored by rose communications

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