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tv   Charlie Rose  PBS  July 23, 2010 11:00am-12:00pm PST

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>> charlie: welcome to our program. tonight, a "charlie rose" special edition. in the 10th episode of our brain series, we look at the disordered brain. >> today we're going to discuss these neurological diseases and we're also going to see that a fundamental difference between neurology and psychiatry is that by and large we don't know very much about the anatomical underpinnings of most psychiatric disorders. we don't know the neurocircuitry that's responsible for schizophrenia and bipolar disorder. we have remarkably good insight into the neurocircuitry underlying most neurological disorders. >> charlie: the 10th episode of the "charlie rose brain series" underwritten by the simons foundation. coming up. the "charlie rose brain series" is about the most exciting journey of our time. understanding the brain. made possible by a grant from the simon foundation. their mission is to advance the
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frontiers of research in the basic sciences and mathematics. funding for charlie rose was provided by the following. ♪ >> additional funding provided by these funders. >> and by bloomberg. a provider of multimedia information services worldwide. >> from our studios in new york, this is a special edition of "charlie rose." >> charlie: tonight, we continue our journey through the fascinating world of the human brain. when working properly the brain performs sophisticated tasks smoothly and easily, allows us
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to move and speak and interact with our surroundings requiring only a minimum amount of effort. but when the brain is damaged, its true complexity is revealed. our subject this evening is neurological disorders, these include parkinson's disease, stroke, huntington's disease and spinal cord injury. these conditions have taught us more about our brain than any other kind of brain disease. through parkinson's, we have learned about movement. through stroke, we have learned about speech. and through spinal cord injuries, we have learned how thoughts give rise to actions. neurological diseases have been a topic of research for centuries. but only recently have we developed effective treatments. this evening we will meet a group of scientists who have developed ways to repair or bypass the disordered brain. john donahue. his work allowed paralyzed patients to move and communicate using only their thoughts and a machine called a brain-computer interface. he is a professor at brown university and the cofounder of
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a company called cybernetics. john krakower. his work explores how the brain explores movement and how movement is recovered following a stroke. he is an associate professor of neurology and neuroscience at columbia. nancy banini. she subjects the genetic basis of disease by performing experiments on fruit flies. she is a professor at the university of pennsylvania and a howard hughes medical investigator. joining me from atlanta is melan delong, an expert on parkinson's disease and a pioneer in the growing field of deep-brain stimulation, a professor of neurology at emory university school of medicine. our co-host is dr. eric kandel, a nobel laureate, a professor at columbia university and a howard hughes medical investigator. i am pleased once again to have him here to help me understand all about the brain. welcome back. >> thank you. you're doing very well understanding the brain.
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>> charlie: what a journey it is. tell me about today -- the disordered brain. >> last time, we discuss -- >> last time, we discussed psychiatric disorders. today we're going to discuss neurological disorders. disorders of the brain. one of the things youwant to explore is how are they different from one another. there are two fundamental differences. one in the nature of the symptoms. and two, in anatomical location. in terms of symptoms, there is overlap but from a simplified point of view, you could say that psychiatric disorders deal with enhancements, exaggerations of our everyday life. we all feel despondent periodically. we all feel hopeless and worthless when an experiment doesn't work. doesn't work. you see in depressed people.
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the mirror image when we have a wonderful roundtable discussion and we see an extension of that in manic disorders. even schizophrenia, the hallucinations and delusions, we have examples of that in our dreams. by contrast, neurology differs in two ways. in terms of symptomatology. we see fragmentations of symptoms. in parkinson's disease we see a dramatic slowing of movement but in addition we see the appearance of behaviors that we don't normally see otherwise. with a lesion of the parietal lobe, we see neglect of a whole side of the body. just absolutely remarkable. a denial that it's there. but perhaps an even more fundamental distinction is anatomical. we know very little about the anatomical location of psychiatric disorders. one of the brain regions that are involved in schizophrenia and depression -- we're just beginning to explore that.
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with neurology, we have an amazing understanding of the underpinning of neurologic diseases. and we've known this for years. when i was a medical student, in the 1950's, clinical neurology was known as the medical discipline that could diagnose everything and treat nothing. this has changed dramatically. as we're going to learn in this program there are major new treatments coming along in neurology that have revolutionized treatments in various neurological disorders. parkinson's disease. stroke. even spinal-cord transsections. one of the interesting things about it, this progress, again, has involved finding out more about the location of specific neurological diseases. it's location, location, location that counts in the brain, and the history of how we localize functions itself is so fascinating. it began around 1860 with paul
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broka. paul broker was interested in dysphaseias and much of what we learned came from the study of language disorders. broka encountered an interesting patient one day. he had a language disorder which took the form that the patient could not express himself satisfactorily. he could understand language but he couldn't make himself understand. this was not a paralysis of the vocal cords. he could hum well. he could not express himself in language. >> charlie: he could understand. >> he could understand perfectly well. when he kied died and came to autopsy, broka examined him and found a lesion in the front of the brain. he wanted to talk about this to his colleagues so he had to give it a name. in all modesty he named it after
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himself: he found invariably they had a lesion in the front of the brain and invariably the lesion was in the left side and this caused him to realize one of the major insights we have in the biology of the brain. we speak, he said, with our left hemisphere. the left hemisphere specializes speech. this galvanized the scientific community. people began to look for others. two german investigators working on dogs found that there is a systematic representation of body movements on the surface of the brain called the motor cortex or the motor strip. if you stimulate one part of the motor strip your face moves, you stimulate another your arm moves, stimulate another the leg moves. a systematic representation of your body movement on the surface of the brain. this is extraordinarily
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exciting. a few years later, in about 1875, another giant came on the scene. carn bronika. he made a fantastic discovery. he found another language deficit, another aphaseia, but this was a difficulty understanding language not expressing it. so this patient could express language perfectly well but he couldn't understand language. when he came to autopsy, vernic examined him and found a lesion not in the front of the brain but the back of the brain. >> charlie: left hemisphere but in the back? >> left hemisphere but in the back. he had to name it so he could speak to other people about it and he called it vernic's area. he said to himself isn't it interesting. we're dealing with a complex function like language. this involves at least two regions. one for understanding language and one for expressing it.
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like a sensory area and a motor area. he looked to see where they were located. he realized that the vernic area, the area he worked on was at the back of the brain. this is where sensory information comes in. >> charlie: understanding is where the sensory information comes in? >> exactly. information from reading or hearing, feeds in from the back of the brain into the auditory cortex and the visual cortex. these two areas converge onto vernic's areas and put that information into a code for understanding language. he also knew there was a connecting pathway called the vakiculas. the information goes from the sensory areas to the vernica's areas to the brocha's areas. this is an anatomical pathway. that question that you raised made him realize a very profound
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thing. he said i'll bet you one can get an aphasia, a language deficit without damaging broeka's area -- broca's area by interrupting the pathway between the two. under those circumstances, the patient understands, the patient can speak but there is no connection between the two. it's like an occasional presidential press conference. information comes in, information comes out but there need not be a connection between the two. >> charlie: let me ask about this too. where is the genetic understanding taking us? >> in addition to understanding the areas involved in speech we have a very good understanding of the areas involved in movement, and delong has discovered still another area important in the baizeal ganglia
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for parkinson's -- in the basal ganglia for parkinson's disease, using deep-brain stimulation to produce dramatic improvements in parkinson's disease. john donoghue, you mentioned the motor strip. they fire in a characteristic way when you pick up a glass of water. he realized he could use that information to drive a computer. so if you want to pick up a glass but you're paralyzed and you can't do it, that information from your motor cortex can go onto a computer that can drive a robot to pick up that glass of water for you and bring it to your mouth. >> charlie: this is extraordinary and it must have enormous potential. >> it has tremendous potential. >> charlie: if you can think, you can do. >> exactly. it gives additional confidence in the fact that we're reading reading the brain correctly. john krakauer thinks the period
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of plasticity involved in stroke is greater. there is a lot of genetics that we understand about these neurological disorders and nancy banini has taken these genes that are disordered in neurological diseases and put into flies -- a terrific experimental system where we can study the mechanism of pathogenesis. how does the disease come about? so we're going to have a marvelous evening together. >> charlie: all that you wanted to know about neurological diseases, the disordered brain both neurological and psychiatric. we go now to our panel. let me begin with you, john. >> on what eric said, the study of neurological diseases is important for two related reasons. one is that they help us gain insight into how the normal brain is put together because in everyday life our behavior seems so seamless, so easy. it's not until we have an injury to the brain that we suddenly
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see how, in fact, this seamless behavior is made up of component pieces. and so we can gain insight into those components and how they actually are organized in the brain in neurological disease. in the second related area is by studying neurological diseases we can get insight into treatment so i would like to sort of give two examples of the kind of insight we can gain from studying neurological patients, and i'm going to use this brain as an example. a big debate raged in the 19th century between two camps. one camp that thought that brain function was divided into localized components and another camp that thought the brain did everything holistically, and interestingly, that debate goes on today, but -- and the reason for this debate was because it all depended what kind of disease you decided to study. so for example, if you get a stroke in this motor strip here, you develop a paralysis in the limbs on the opposite side of the body. but otherwise, you're ok. you think ok. your language is ok.
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it's just the limb on the opposite side of the body that is affected. so that was a very strong case for highly localized function. but there are other kinds of lesion that cause a much more diffuse, broad set of abnormalities which made it very difficult to believe that all of those could be actually controlled by one region so for example, you can get something called neglect, especially when you affect the right side of the brain and you get the inferior part of what is called the parietal lobule, and these patients have great difficulty orienting and reacting to stimuli in one half of the visual space or one half of their body, in this case the left side so for example if you you touch them after this lesion on the left side you ask where you're touching them, they'll say my right. when you walk into the room from the left, they'll go "hello" and turn their head to the right. so profound cognitive problems caused by a fairly focal lesion. in some cases thing is very local and you get a local
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effect, that's why some people thought it was localized, in another another case you have a focal region and you get a more global abnormity so you can see by continuing to study patients with imaging techniques that allow us to see this architecture, we can actually learn fundamental principles about how the brain is put together. so parkinson's patients have a part of their syndrome is bradykinesia. they move slowly. so a colleague of mine asked a question that one tends not to ask. why do parkinson's patients move more slowly? and the converse question is why do we move at the speed that we do? so i would like to do a little experiment to show that. if each of you reaches for a glass of water. you will find that all of us pretty much reach at the same speed. so on the one hand, you voluntarily decided to reach for the glass, but on the other hand, you unconsciously picked a speed which is very similar to all of ours, and what we think
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might be happening is that they have a different balance between how much effort is required to reach the glass and how worthwhile it is to reach the glass and there unconsciously the balance has moved toward it being too effortful to reach the glass in the time that we do. >> charlie: give us a sense of what the history of what we have understood and how we've treated parkinson's and where we are today. >> james parkinson, in 1817, described parkinson's -- was the first description. slowness of movement. characteristic tremor. and the shuffling gait -- in fact, he called it the shaking palsy because of the tremulousness and slowness -- palsy needing a weakness. he did not name it after himself. it was 150 years ago from that time, roughly, that the first really effective treatments were developed, and ironically, these were not medical but surgical --
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neurosurgical procedures. neurosurgeons, desperate it find treatment for patients with uncontrollable, excessive tremulousness were able to identify, largely by trial and error, specific regions in parts of the deep-brain circuits and this involves the basal ganglia and the thalamus, in the 1960's there was a remarkable series of discoveries, the first the presence of a substance called dopamine in the brain and the basal ganglia and the evidence that it was depleted in brains of -- in brains at autopsy of parkinson's, this led led to the attempts to replace that in patients by giving a drug called levodopa. it's a precursor of dopamine.
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it actually reaches the brain and this was viewed as a cure. its a matter of time that the other foot dropped, so to speak and began to realize that with -- after the honeymoon period of a number of years often patients would develop involuntary movements, we call them dyskinesias or we call them motor fluctuations where the medicine would wear off abruptly and these combinations of motor fluctuations, sometimes failure to respond and the dyskinesias would be very disruptive of movement, and this called for really alternative approaches. during the 1970's and 19be80's, there was a remarkable series of -- i would say studies and progress in understanding the motor -- better the motor system, the anatomy and physiology, and one of the most important things i think
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relevant to parkinson's was the understanding that the basal ganglia which were depleted of dopamine were doing something more than just providing some substrate for movement. in fact, it was commonly believed at that time that the basal ganglia were primarily movement because of the association with disturbances of movement and basal ganglia dysfunction. we were able to show that in fact, it was a restricted part of the basal ganglia that were really involved with movement and that other regions were involved with higher function -- the key to finding -- understanding the mechanism of this was actually to lesion -- to destroy a small part of the motor circuit within the basal ganglia, and this is a region called the subthat willammic nucleus. details are not so -- called the subdthalamic nucleus.
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>> this area had an essential role in the control of movement and in parkinson's disease and that's what led you really to start thinking about using deep-brain stimulation for that. >> we were at first, and i think others, most concerned not to lesion the subthalamic nucleus, was the discovery of the deep-brain stimulation when applied to the subthalamic, by the 1990's deep-brain stimulation had virtually replaced all lesioning approaches to treating parkinson's disease. this was the great advantage of deep-brain stimulation was the nondestructive, reversible and adjustable nature of this treatment. i'm going to show you one of our first -- or earliest patients. this was our 17th patient who had received deep-brain stimulation.
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we'll let this roll. >> the disease had gotten so bad her face almost expressionless and her legs almost useless. the woman who once was always on the go could barely move, confined to a wheelchair. do you ever wake up in the morning and forget that you have parkinson's for a moment or two? >> not now. not recently. because my every waking hour is terrifying. >> but on the morning of the surgery, sybil was confident even as nurses fitted her with a head frame to help guide surgeons during the -- surgeons during the operation. as they wheeled her to x ray, she was in good spirits. deep-brain stimulation comes down to one thing. location. to help pinpoint the region of sybil's brain where he would be working, neurosurgeon roy bakay used imaging. finding the target area held the key to sybil's future.
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if the stimulator is implanted correctly, she may finally be free of the tremor and pain that have haunted her for years. but if the placement is off, the results could be devastating. finally, the doctors think they have placed the electrode in the exact location that will help sybil. when they turn on the stimulator, she suddenly shows an astonishing range of motion in her legs and hands. there you go. up and down. drop it down now. pick it up. great. she couldn't do that before. how about the hand? can you open and close the hand for me now? good. >> when dr. vitek turns off the stimulation, sybil's tremor and stimulation return. can you move it up and down? >> it was only a month after her second surgery when we caught up with sybil again. when i talked to you before you
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had any surgery, one of your biggest problems was that you couldn't turn over in bed. >> i was really concerned about that. but now, i roll back and forth. you can't stop me now. >> now, the woman who never wanted to slow down doesn't have to. what can you do now that you couldn't do before? >> oh, good heavens. >> sybil and alvin had hoped for a lot from the surgery, but the outcome was better than they could have imagined. >> charlie: underline what that tape shows us. >> i think the most important thing is that it shows the clinical benefits and it shows the profound effect on quality of life. sybil -- this simple video shows that better than any. >> it also shows how scientific the treatment had become. because they first introduced the electrode for deep-brain
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stimulation on one side of the brain and it stopped the tremor on one side of the body. >> right. >> then in order to control the other side, they -- second, as an afterthought, put the electrode in the other side and stopped it on the second side of the body so the patient now was free of tremor. she moved from being essentially paralyzed to jumping and dancing around with the family. an extraordinary improvement. >> charlie: does it work on everybody? and what have we learned about it? >> yeah, that's a very important point. this does not work for everybody, and it's not a cure. it's a completely symptomatic kind of treatment. if the battery should fail or the wires become disconnected, it can happen but not common, the benefit is lost, almost immediately. >> charlie: let me turn to nancy now and talk about genes and how they're involved in the diseases we're talking about. >> right. so another approach to get toward these diseases is to take a very basic research approach and use animal models, and an
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example of an animal model is actually drisophila, the fruit fly. it has powerful approaches. for many of these human degenerative diseases, for many diseases there are gene-inherited forms as well as the more spontaneous, so-called sporadic forms bew but we have ways in the familial situation to get that gene and then we can study that gene so for parkinson's disease one of the key genes identified is the gene alphacynucleen. inherited in rare forms of parkinson's disease. it turns out that alphacynuclien accumulates abnormally in the brain of all parkinson's disease patients. this has allowed the idea that even though you find these genes through these rare, inherited forms -- >> they're instructive about the whole thing. >> that's right. they're going to tell you about
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the disease in general even though most of the disease is sporadic. so with the gene, you can then study the ways in which that gene may cause disease, and that's called studying the pathogenesis. and animal models are really key experimental tools in this and there are many different types of animal models that you have touched on in the series such as the nematode or the mouse and i'm going to talk about flies -- that's the system that we use, the basic fruit fly. the fruit fly was really used and developed as an experimental organism by thomas hunt morgan at columbia university, and he was interested in basic aspects of chromosomes in heredity. later, seymour bensor, he opened up the world of the brain in the fly and he focused on genes that were involved in behavior and just like maylon talked about there are regions of the brain that are isolated but they also connect to other regions of the brain. genes don't work on their own
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but genes work in a network with other genes and these are called gene pathways. so in fact, we now know that for many processes, not only genes but entire gene pathways are shared between flies and humans. so that means that we can then take that gene and study it and ask how it may be functioning and hope to learn not only about flies but really what we're interested in -- we're interested in people and humans, that's right, and so the fly had been classically used to approach development, and more recently it's become very popular for behavior, and we decided, why not try can human disease. so the idea would be that whereas these diseases in humans can take decades for their onset, in flies we can give a fly a phenocopy or what it looks like to have parkinson's disease in days or weeks so we can grow many flies and we can speed up
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the whole process in order to really study that mechanism. so on the next slide, shows sort of a section through the fly brain where we're studying some aspect of parkinson's disease. so an idea is when you we have the gene, like alphacynuclien, we can put that gene into flies and then ask can we get an effect in the flies that looks like parkinson's disease? as maylong talked about, dopa mine is important in parkinson's disease so we can express that gene in the neurones. so the top panel shows clusters of dopaminerjic, we see fewer of those cells staining for this neuron for dopaminergic neurones. if we express in those cells, they become compromised and sick
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and by expressing this gene associated with human's parkinson's disease we can get effects in the fly that look like core effects of parkinson's disease. i would like to show another example that's showing an effect on climbing behavior. so this is using a gene in the fly that's involved in a.l.s., so a.l.s. is another -- >> amyo trophic lateral sclerosis. lou gehrig's disease. >> it's another very debilitating disease and leads to loss of voluntary movement control and total paralysis. if we look at the behavior of normal flies, normal flies will climb upwards. they have this robust negative geotactic response, but the flies that are defective in this human a.l.s. gene, these flies are alive and they are moving but they can no longer climb, so
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this is a remarkable example of sort of a fundamental phenocopy or we're mimicking the disease in the fly situation. so of course, in the real laboratory we take a very comprehensive approach to this, so we look at many, many different aspects of what it looks like in the fly to express one of these genes and we're asking how many features look similar to the human situation so that we can say how well does the fly show the fundamental features of that disease. so in this situation we're sort of using the power of conserved pathways and conserved genes in order to approach the really complicated problem of human disease. >> charlie: let me move to john do noghue. >> what i would like to do is go back to the idea of localization in brain circuits, not the brain circuit for language but the one for arm movement and how we've
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taken the fundamental discoveries in that area and turned it into the ability to help people who are paralyzed move again. so first i would just like to show that -- what goes wrong in paralysis. so basically, in this slide it shows there are two kinds of major roots of paralysis. one is that the central motor pathways are disrupted and the other is that the peripheral motor pathways are disrupted and in both of those cases the brain is intact and functioning but its connection to the outside world is broken, and what we're trying to do is -- would be interested in doing is reconnecting the brain to the outside world. we can't fix those pathways. we don't know how to fix them yet. instead of using a biological repair, we can use a physical repair, truly wires and fiber opticic connections. we relied on fundamental knowledge. localization. eric brought up this idea there is a region in the motor cortex and there is a region near the top of your head about the size of a quarter that controls your
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arm, and that we've known since about the 1870's. this is a great area of discovery. interestingly what the neurones in that area did was unknown until -- what the nurons in that area did was unknown until ed everetts listened in on a single neuron and asking what it did. i think i have a single neuron. i can hear the popping. you're listening to a sound related to movement and those popping noises are called action potentials or spikes and that's the code of the brain, and neurophysiologists try to decode the brain and make sense of movement, and from studying the behavior of animals we learned that the motor cortex arm area is very interested in producing commands of when to move and which way to move -- left or right.
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so we had some insight from these years of experiments. for about the next two decades, we explored those areas and we learned that really, this information was encoded not in a single neuron, but in populations much like the information in a symphony is not encoded by the second violinist but you have to listen to the whole orchestra. what was severely lacking was the ability to try to capture many cells at once like listening to the whole symphony so we developed an electrode array, instead of one a tiny implant of many electrodes that's shown on this slide. it's actually something about the size of a baby aspirin. it's implanted permanently in the arm area of the motor cortex and then it comes outside and the signals are brought to the outside in its current version, it's very tiny, not even the size of a penny. at that point we said here we have technology that allows us to peer into the brain, we have at least a primitive understanding of what that parst brain, the arm area of the motor
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cortex is trying to do, we can take people who are paralyzed, that is able to think about movement but not able to move and connect their brain back up to the outside world. so i guess what could be seen as a rather bold step but we sought f.d.a. approval and we were approved by the f.d.a. to study a small number of severely paralyzed people, tetraplegics that can't move their arms and legs, and we implanted five people so far in this small trial, and i think just by illustration i'll show you one of the first patients, his name is matt nagel, playing a video game. he's supposed to hit those things -- treasure chests and avoid the squares called goblins, a video game called goblin. he was playing the video well but not great but in fact matthew was enter injured in his cervical spinal cord, completely disconnected the brain from the entire body, he has a chip in his motor cortex and by thinking about moving he can make the cursor move. >> amazing, amazing, amazing.
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>> again, it's a true example of taking the information from basic science -- we had all the pieces and we just put it together so that we could reconnect the body to the outside world. >> charlie: what are the possibilities of this? >> you will hear more about the possibilities. i think we want to give a couple of examples that i think take us sort of step-wise gone through this, so one step is can you control something physical? we thought of something physical. a mechanical hand. so matthew can't control his own hand so we brought a mechanical hand. here we're seeing a video of matthew thinking about opening and closing a hand and there he is opening and closing his hand. had a very profound effect on him because it was the first time in years that he had actually moved anything physically himself, but he's doing it entirely with his mind. then to extrapolate that a bit further, we asked, "well, could you control something practical like a wheelchair?" this is actually a lady who has what's called a brain-stem stroke. it's a little above the spinal cord. she's not only unable to move, she can't speak.
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what she's doing here is using braingate, this chip, to control that wheelchair so it's wirelessly beamed over to the wheelchair and actually the control system is that little computer mounted on the wheelchair, and i had asked her to drive the wheelchair over to the door. she had practiced for about five minutes before this, and here she is sort of -- not very gracefully but driving it over toward the door and you will see it progress up over to the door. and, of course, the control isn't good enough. we wouldn't have her in the wheelchair, we had her do it remotely. so at this point, we have shown in each of several different disorders -- that includes spinal-cord injury, in stroke, and even in a.l.s. patients that it's possible to decode the brain, sense the signals, decode the brain and connect them to devices. we're not there yet where these are available for everyday use but matthew recorded some of his comments about his views on the
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technology, and i think if you -- i think this video will just -- he can narrate it and tell you what he thought of the technology. >> i envision this giving me more independence as far as changing the television. opening my shades. turning on my lights. or calling the nurse -- what the nurses have to come down and do for me -- it will give me a sense of independence. not as much as i would like, but it would give me some independence. for me, that would be wonderful. >> what is also so wonderful about this is not only the clinical effect which is so dramatic, but it really shows that john has learned how to read the brain. how to use the information from the brain to drive a device. so that itself is a major insight that you can make sense out of the action potential
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sequences in the brain. >> it really brings us to john's aspirations here, john krakauer of what you hope to do with stroke. why don't you outline what you are thinking about that. >> it follows very nicely, because the very same plasticity in these extreme cases where you are disconnected, where you are going to have to bypass the severed pathways and control an external device with this plasticity, in patients who have stroke, for example, where they still have some residual movement left, the question i ask is a similar one. can you somehow augment their plasticity and sort of enhance their recovery? and so there are a number of points to make about that. most patients, after injury, less extreme than we just saw, recover to some degree and they recover most of the time within the first few months after stroke, but not completely. and we know from animal models, we were talking about before that this seems to be because of
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a time window of plasticity that finishes after about three months, in humans it's about four weeks in rodent models. what we want to know is can we use technology to try and take advantage of this period of plasticity in patients after stroke? there are two kinds of technology thar being used increasingly now so here is a robot -- a robotic device that attaches to the affected limb of a patient after stroke and what this robot can do is it can give varying degrees of assistance to the patient so that when they start to make a movement, the robot can give them 3-d assistance, and as they get better, as they begin to understand the kind of movement required of them you can begin to take away the robot's contribution. so the idea would be to take patients early after stroke and with the use of a robot which can give you hundreds if not thousands of repetitions, and we know that large amounts of
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practice are required to actually interact with this plasticity to get recovery. so what we need is some sort of device that doesn't get tired and can be programmed to give you hundreds of thousands of repetitions and do it early, and this is what these robots can do. the second kind is to do something noninvasive not unlike what we heard from john, with patients that are less severe we don't feel like we have to put electrodes into the brain itself, we can stimulate the motor cortex with electrical or magnetic stimulation, on this slide you see this figure-8 coil and what you do is you put current through the coil which generates magnetic fields which are at right angles to the brain and those magnetic fields induce current in neurors and stimulate a motor cortex. the other one, instead of using magnetic fields you can use a 12-volt battery over the head and that can increase excitability of motor cortex and these are two ways to augment activity and plasticity over targeted areas of the brain and
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a lot of studies now are showing that these can increase and improve performance. so the dream would be the cocktail would be to take a patient early after stroke in this window of plasticity, hook them up to a robot and stimulate their brain at the same time and potentially give them some sort of drug and with this cocktail ramp up the amount of recovery that could occur in these patients early after stroke. >> charlie: let me go back to maylon, this notion of where you see the future of the kind of research you are doing with deep-brain stimulation. >> deep-brain stimulation is now being exported if you will from the parkinson's tremor field to other movement disorders -- has been successfully for dystoneia and other disorders of -- dystonia, and other disorders characterized by excessive movement, remarkably for orders that really are psychiatric in nature such as
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obsessive-compulsive disorder, depression and tourette's syndrome which is a blend of movement and psychiatric disturbance. so i think the theme here is that we stimulate the motor circuit for movement disorders, we stimulate this emotional reward circuit for treating these psychiatric disorders and it seems to be more circuit-specific than disease-specific, so we use the same targets, the same stimulation parameters for all of these conditions -- granted that this is fairly large-scale kind of stimulation. >> there is an interesting sociological point here, and that is that helen mayberg whom you had on this program recently introduced deep-brain stimulation for depression, stimulating this area 25 that she found hyperactive and here is a psychiatric illness that was treated successfully by a neurologist. and why is this so?
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why weren't psychiatrists doing this? that is the culture of the two fields are different. neurologists intrinsically, from broca and vernica on have thought of anatomy, anatomy, anatomy, location, location, location, psychiatrists have not thought in anatomical terms until lately. >> the main thing, charlie, about this technique is it has given renewed hope -- >> immense. >> for patients with disorders. >> the four people here have shown that in relatively short period of time, one or two generations, neurology has moved from being a field in which with the exception of epilepsy nothing was treated effectively to a point where it's really making major strides forward in treatment. i think this is a major, major advance. >> charlie: pick up on terms of -- >> you might ask, i was talking about simple systems, using the fly and recreating a human
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disease in the fly and you might ask what's the point of that? the point is that you can use the powerful genetic tools that are available in the fly to define genes and gene pathways and even drug compounds that can interfere with that, so for example, in parkinson's disease, alphacynuclien accumulates abnormally so it looks like the protein undergoes an abnormal folding process, clumping in the neurors, and this feature of abnormal clumping of disease proteins is a future of many human degenerative diseases so for example in alzheimer's's disease there are plaques and tangles so this is a common feature that the proteins seem to build up and they clump abnormally in the cells and this is probably leading towards the toxicity -- the pathogenicity, so we have, and flies have, very conserved pathways that are very critical to help proteins take
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on their normal shape. so to prevent this kind of clumping. these are called molecular chaperon pathways so these are helper pathways that can help proteins fold properly. so we consers if alphacynuclien is causing toxicity potentially by clumping abnormally, what would happen if we gave the flies more helper proteins? in the top panel the fly has a set of dopaminergic. now in the bottom panel, we can see what happens when we add this helper protein -- this really great molecular chaperon called hsp-70. we in fact restore the system back to normal. we no longer see the compromise of these dopaminergic neurons. this works not only in this
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situation but it works in other fly neurodegenerative disease models of which there are many now and it also works in mouse models, so this is one example of where we sort of thought about what was happening, we stepped back from that and we made a really good guess of what might be involved in the process. >> charlie: john, let me finally come back to you, and tell me where the frontier is in terms of brain interface -- brain-computer interface. >> it's not just brain-computer interface. the future is to connect first, i think, for people who are unable to move and for whom we can't restore their full function to connect them to external devices that are useful, that can help them in their everyday life. what many people don't appreciate is how devastating paralysis is, especially the tetraplegia that we saw. they can't do anything. imagine if now could you could control a very dexterous robotic arm that could get you a drink of water because you can't drink without somebody bringing it to
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you. it's not a paralyzed person but it's an able-bodied engineer, my colleague joran vogel and one of his co-workers, patrick vandesmut and they're showing this sophisticated robot from the german space agency that he's controlling with a mouse with his actual arm underneath the table but imagine the person could use their brain to control this and take a drink of water using this robotic arm under brain control so we're actually under way doing this asking our participants to try to accomplish this using a robotic limb. it will be slower than normal. it won't be as dexerous as normal. but we are very encouraged -- it won't be as dexterous as normal but we are encouraged that we can once again have people interacting with their environment but the next step for us is rewiring the brain back to the muscles with physical components. it is possible to put stimulators into the muscles. bring the brain signals to the muscles. and so therefore, someone thinks, and moves. so our ultimate dream, which is
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very far away, i'm not sure any of us at the table will actually ever see this would be we would be sitting here one day and one person would say, yes, i have had a spinal-cord injury, i have been rewired, i have brain gates, i have wires, stimulators implanted but we will play tennis afterwards. this is very far out, but we're coming. we have actually done, in a simulation with a patient the ability to make simple movements of their own arm and this looks quite feasible. so i think -- the future is very bright for a physical repair of the nervous system. >> charlie: what i always like to do at the conclusion of these conversations is to ask the one question -- what is the thing that you most -- the question that you would most like to see answered to see realization of what you are talking about? >> this has a whole set of problems. currently patients have a plug on their head, they have a cable going to a big rack of computers and we have the mystery of
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actually what the brain is doing. i have the problem of wanting to know what the brain is actuallying doing, not what we think it's doing, i want to be able to make a device that will be hidden inside the body much like a coclear implant or cardiac pacemaker and i want to take the big chunk of computers and shrink them down to something you might wear in your phone like an iphone. >> what are the questions you want answered? >> fucome president point of view i do which is to look at a -- >> if you come from the point of view i do which is look at a simple system you're looking at similar, we can look at the fly but they look more similar than different so our idea that we're going after is that there might be common gene networks that underlie multiple different diseases, and if there are, then it means there might be genodes that we could attack for therapeutics, so we would like to identify those gene networks that might tie multiple
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different diseases so that we could go after those in a therapeutic sense. >> charlie: john? >> yes. i have a comment and a dream. the comment is that i think the great message that this show can put out is that the nervous system and neurological disease and neuroscience seems to benefit greatly from multilevel explanation. we've had genes, proteins, receptors and that's not just about taste -- the great point that psychiatrists and neurologists seem to have their own level of entry into understanding but the profound point is we need to attack all these levels and have research attacking all these levels and having everyone interact. that's my main comment. it's a profound thing about biology versus physics, for example. >> maylon? >> my real question is kind of where i started this business. i was trying to understandingnd the basal ganglia. >> charlie: right. >> i do not understand the basal ganglia. i understand how they can cause all kinds of problems when they
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don't work and how we can help with that, with these ways of modulating activity but i think we really don't understand exactly what they're doing and i think the evidence is pointing more and more toward something we talked about which is plasticity and learning, and i think this probably will be a more important and profitable venture than trying to figure out what we have been studying to this point, and it's a long -- it's a big topic but that's where i think the answers will be. >> charlie: my colleague. >> i would like to see the kinds of logic we've heard tonight around this table applied more extensively to psychiatry. i think psychiatry is lacking in emphasis on anatomy, on how different regions function electrophysiologically and i think that kind of thinking needs to happen on a routine basis, and one of the things we were discussing before we came in here is to what degree ought
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to be a common training for neurologists and psychiatrists -- at least for the first several years of their career. >> charlie: is it psychiatry that's not receptive to this or what? >> some of my best friends are psychiatrists. these are cultures that have grown up over a long period of time and it's difficult to bring them together, although the leaders understand that this convergence is necessary. >> charlie: remarkable panel. we reconvene here in two months. what will we talk about? >> we're going to speak about the role of the brain in decision-making. you, charlie rose, make a lot of decisions in the course of your life. you make personal decisions about whom you form partnerships with. you make social decisions about what clubs you want to affiliate with. you make emotional decisions of all sorts. moreover, not only do we begin to understand that, we're beginning to understand how people make economic decisions. this is allowing a dialogue between economists and brain scientists. to see what are the mechanisms
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that underlie economic decision-making. do you want a short-term gain? a small gain that you can be fairly sure of? or a much larger gain that is a little bit chancier? >> charlie: the larger one. >> what are the kinds of strategies you are going to use? moreover, we realize that certain lesions of the brain make you irresponsible as far as decision making is concerned. so emotion plays an important role in this and disorders of emotion can interfere dramatically with your ability to be a rational decision-maker. so we're going to consider this next time. >> charlie: this is remarkable stuff, it really is. >> wonderful stuff. >> charlie: what we're learning -- it's like this most amazing organ, and we're just beginning to understand it, and we find out that we're building on the history of great people who had remarkable insights without gunfire the tools that we have. >> this is -- without the tools
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that we have. >> these people did extraordinary work with primitive tools. being creative and bright helps. >> charlie: and we certainly have that. thank you, my friend. when we come back, "the deciding brain." see you in september. ♪ captioning sponsored by rose communications captioned by media access group at wgbh
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>> "the charlie rose brain series" is about the most exciting scientific journey of our time. understanding the brain. the series is made possible by a grant from the simon foundation. their mission is to advance the frontiers of research in the basic sciences and mathematics. funding for "charlie rose" was provided by the following. additional funding for "charlie rose" was also provided by these funders.
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