 Have you seen Dimazio's new book? That's what I had yelled at me the other day. It was Richard LV yelling at me. Have you seen Dimazio's new book? He said, what's that? He said it's called Descartes' error. I said, I'll love it. Anything antithetical to Cartesian thinking, I'll love. So I went over there to the bookmark and picked it up and who should I run into but my friend and colleague Mark Kruger, who is also there trying to find Descartes' error. We purchased the books together. I read mine. We'll see, Mark. It's a wonderful book. I'm going to call this a landmark. For years in education, we have taught that cognition, affect, and cycle motor are separate domains. We've taught them as stair steps, beginning with knowledge, ending with synthesis and evaluation and cognition. This book calls into question all of those old paradigms. I invite you to interact with it and see what you think. I want to introduce now Antonio R. Dimazio. He has a medical doctorate and a doctor of philosophy. He is the M. W. Van Allen Professor of Neurology and Head of the Department of Neurology at the University of Iowa College of Medicine in Iowa City. He is also adjunct professor at the Salk Institute for Biological Studies in La Hoya. He is internationally recognized for his research on the neurology of vision, memory, and language and also for his contributions to the elucidation of Alzheimer's disease. The center that he and his wife, Hannah, created at Iowa, is acknowledged as the leading facility for the investigation of neurological disorders of mind and behavior. He is a member of the European Academy of Sciences, NARTS, and of the Royal Academy of Medicine. A fellow of the American Academy of Neurology and a member of the American Neurological Association. He received the Beaumont Prize of the American Medical Association and recently shared the Pasola Prize with his wife. May I present to you Antonio Dimazio. Thank you very much, Paul. I must tell you before I start that Paul just asked me to sign his book and I said after your introduction, but now I will sign it. I would like to thank you for your very kind introduction and I would like to thank the organizers of this beautiful conference for your hospitality, but mostly for inviting me. It should be fairly obvious that we are all having a great time on this side of the stage and so I think we should congratulate the casting director of this play because I cannot think of many other groups of colleagues and friends that I would rather be with today than the ones that are gathered here. Well, let me say that we have a title for this conference, The Unlocking of the Brain, and it's quite obvious from everything one hears about brain research and from the fact that several thousands of people are here listening to us that there is an excitement about what we call neuroscience. And I would like to tell you first of all what I think the excitement is all about from my perspective and of course many many reasons for that excitement. But the main ones for me is that for the first time in the history of science all levels of neural organization are accessible to scientific inquiry. This is really the first time that it is happening in a consistent way, but it's quite obvious and it will be obvious to you by the end of tomorrow that everything from the molecules that Eric Kendall and Anders Bjorklen will talk to you about tomorrow to the systems that David Ubel and I and Pat and Oliver Sachs will tell you about can be now approached. And what is most exciting about it is that not only can you do research in traditional scientific sense of the term at all those levels, but you can establish interrelations between those levels in a vertical way. And we have for the first time in front of us the prospect of joining the fields that have traditionally been called or subsumed under biology and the fields and the aspects of inquiry that had been subsumed under the term psychology. And when we do that we also have another great prospect is relating the ensemble of both biology and psychology in modern terms to the fields of knowledge that have been traditionally in the social sciences and that really relate to and to other sciences that relate to the physical and social environment with which we interact. So it's a time of excitement. And since there was a mention of Descartes already, let me say that it is a time in which the views that quite well known views of Descartes on this matter are really falling by the wayside. If Descartes is known for something and is known for the separation between biology and the mind and that is certainly falling before our very eyes. Now let me turn to a little bit of the approaches that we use in the kind of science we do. And there are two that are very important. One is known as the lesion method and another is now also quite well known and it's under the term dynamic imaging. And what we do with these approaches is complement a lot of knowledge that is gathered in the study of animals with knowledge that is gathered in human beings. Sometimes perfectly normal human beings as we are without any medical problem. Other times individuals that have a problem generally a neurological condition has led to damaging a specific part of the brain. And I would like to have a first slide and to tell you that the way in which we do this today is very different from the ways of the past. And the most important point to remember is that we really use lesions in the brain, an area of damaging one point of the brain such as for instance the occipital cortex that David Hugo told you about this morning. We use that lesion as a probe to the behavior of the system that we have hypothesized. So we begin by having a hypothesis about how a collection of areas in the brain ought to work and then we test the hypotheses by placing as it were lesions in different points of that system and deciding whether or not the results of that those lesions accord with our prediction. So in a way there's a commonality of approach with many other aspects of neurobiology. For instance this is not unlike what you do when you do gene knockouts in mice for instance and you are trying to study certain systems. It's not totally unlike what you do with drosophila mutants for instance. And the other main aspects that are different in the current approach to this aspect of neuroscience is that we use many exemplars, many patients that have similar conditions, similar lesions, so that we can really do systematic studies, we can make comparisons, we can control the results. Perhaps most important of all is the fact that we have now, unlike the case in the past, we have now the possibility of knowing about the neuroanatomy, the state of neuroanatomy in vivo that is in the living human brain. So here you have this brain that you're looking at and you see all the marvelous detail of gyros and sulci. You're seeing it in many different views and most of you would be tempted to think that this is really a post-mortem brain, something that came from an autopsy and the meninges were very beautifully cleaned and this was the result. Well, I have news for you. This is actually the brain of Pat Churchland. And so this is obviously a very, very important, very important thing because first of all, we can now say that we can certainly deny the statement that all philosophers do not have brains or that some philosophers do not have brains. At least we know for certain that Pat Churchland has a brain. We knew that, but it's sort of nice to know. And it's also a beautiful brain. It's very perfect. It has all the components. So when she talks to you a little later, you will realize why she's so eloquent. Now, how was this obtained? Well, this was obtained from a magnetic resonance scan with very fine resolution in Pat. It could have been obtained in any of us in this room. And it is done from a marvelous collection of slices. And it was then reconstructed using a methodology that was developed by Hannah de Mazue and random Frank at her laboratory. And what it permits is do these studies, which are really very perfect. And now you're looking at another brain and you're seeing the marvelous detail that this can produce at the computer screen. And you can see how important it is to have the information about the state of that particular brain when we are doing an experiment in a particular person. Now, you can cut this brain, any brain, in any slice in any direction that you wish. And you can do this on the moment at the computer screen. You can relate information from two-dimensional slices, as you have on the right-hand side, to the three-dimensional volume reconstructions of an entire brain. You can do something quite marvelous, is that you can look at a lesion that is in a particular locus. You see David, if I'm luckier than you are. Here it is, a lesion in this location. And you can study exactly the position in which that lesion is relative to landmarks. And you can do it on that particular individual. And therefore, you can quantify the size of that lesion. You can quantify it relative to that unique brain and then relate it to the unique results of the experiment that you have been doing in that person. Furthermore, you can relate all of these landmarks to the skull, the scalp itself. And by doing so, allow for the development of new methodologies in dynamic imaging. One that again has been developed in Hannah's lab. It's called Pat Brain Vox. And she and Tom Grabowski have developed that. And it allows us for the first time to look at anatomical hypotheses in the studies of dynamic imaging using what is called positron emission tomography, or PAT, which I know many of you have heard about from reports in newspapers and television. Now, let me give you a quick example of what one can achieve these days using some of these methodologies. And I'm going to start by telling you a little bit of an ongoing result in the area of language, which is obviously something that interests all of us here. Well, you're looking at a slide, which in our laboratory is known as the Christmas cookie slide. And it shows in different colors the key areas of the traditional map of language regions in the human brain. You have the famous Broca's area, the famous Wernicke's area, which is here. And there are areas such as the angular gyrus and the supramarginal gyrus at an area that goes by a number rather than a name, and that's area 37. Well, this is the state of knowledge of language systems that we inherited from 100 years of neurological case studies. And that was in fact prevalent at the time of my mentor, Norman Gashwin, who revived and continued many of these studies into the late 20th century. It was one in which the prevailing idea was that these different areas acted as centers that were capable of an enormous amount of processing and would do such things as auditory comprehension, the production of syntax, and other such. And it was, as you can see, relatively limited in scope. Only certain spotty areas of the left hemisphere were involved. Well, the news that I want to bring today is that, first of all, it is quite clear now that the way these so-called centers operate is in a very systematic and integrated way. We really do not have anything we can call centers. Rather, we have systems that have multiple components, and they work in concert. And they span large aspects of the brain. Very often they span an entire hemisphere. The second thing is that far more than just these areas are now being discovered using the appropriate lesion method and pet experiments. And let me tell you about something extremely simple. It's a study that has the same kind of simplicity in terms of the stimuli that David Hubel demonstrated this morning. Sort of the equivalent for language of using a bar across the visual field in order to get at the responses of cells. And what we're using in a study that has involved so far 151 patients with damage all over the telencephalon is a task I'm just going to concentrate on one that requires naming, that is the production of a name to a stimulus. And that involves, as you can see up top, stimuli that are divided in different groups. One is of pictures of common entities, things like manipulable objects or animals that you can see out in the street. Another, pictures of unique entities, which are more often than not unique familiar faces or unique landscapes. And another of pictures of actions. Let me just show this very rapidly so that we have an idea of what a patient is confronted with. You have here a couple of screwdrivers of different types. An animal that you will recognize. An action that you will recognize also. Here what counts as not the groom or the person, but in fact the action, the sweeping action of that particular duo. And you have a face that you will recognize also. These are all presented in blocks to these subjects. And let me tell you what we have found and just give you a couple of examples to give the flavor of the enormous selective organization of the human brain. For instance, we have found that there are patients that will behave this way. Here's one patient that shall the concrete entities and ask to produce names will behave quite poorly and will not in fact be capable of coming up with more than about half of the total number of names. And when you compare to the performance of the controls that are matched for age and dedication, you realize that it is many standard deviations away from it. However, look at this beautiful discrepancy. When that same patient is asked to name actions such as phrases the sweeping, the patient has no problem whatsoever. So there is a complete sharp separation between the ability to conjure up the name of an object and the ability to conjure up the name of an action. And this is something that is extremely consistent and is observed over and over again. It is also stable across time when you change the stimuli and you retest the person. Let me tell you that so far we have found out of that 151 pool of patients 14 that have this kind of behavior when the slide was made early three and the lesions systematically cluster in the left temporal lobe anteriorly that is in the front part of the temporal lobe as it were. They're on the left side only not on the right and they are in dislocation. Now for those of you who remember that previous cookie Christmas cookie map, you'll realize that this region was not part of the traditional language areas. So it is in fact in fact part of the system that handles one particular aspect of language processes which is the conjuring up of a lexical entry so that you can produce a name and this is something that is part and parcel of the very large scale system that operates language. Now let me show you something which completes the picture. Here we have another patient KJ that falls abysmally when it comes to coming up with the names for actions that look how it performs when it has to come up with names of concrete actions of concrete entities is as good as the controls. Here there is a very large area of problem. Now let me tell you what the nine subjects that so far have been shown to have the problem with naming of actions do in terms of their visions and their visions are located in left frontal region but never in the temporal region. So what we have here is what is called in classical neuropsychological methodology a double dissociation. Those individuals that have trouble conjuring up the names of objects fail when they have lesions in left temporal lobe systems but those individuals that fail to have that do not have that problem but fail instead to have a problem with actions have lesions in the left frontal lobe system. What this is telling us is in fact something that ought to have been quite intuitive but we didn't do it and that is that the brain honors the distinction between making representations of objects that generally are in fact centered around aesthetic representation of objects in a particular canonical representation and the representations of the actions that those objects can make in space time or the actions that those objects can be made to make in space time and it is not a coincidence that in fact the brain chooses to have the naming function for objects at the very tip of the temporal lobe which contains the end point anteriorly of the chains of visual processing that begin in v1 as David Hugo showed you this morning and that instead it places the ones that have to do with actions at the end of chains that originate in the parietal courtesies which are fundamentally related to properties of movement in space time and the displacement of objects in a three-dimensional space. So this actually makes quite a lot of sense through the point of view of the brain and the interesting thing is that it is coming to us from the results of studies of patients with lesions in different locations. Now let me tell you that this result has now been completed with a study using labeled water 015 in PET, Positron Emission Experiment and this is an experiment that was carried out by Tom Grabowski one of our colleagues and Hannah DeMazio and it's a really heroic experiment in the sense that it now has 28 normal individuals and what the individuals were asked to do was in one condition to look at a name of an object take the word apple and read it out aloud in another to look at that name but come with a generation of the words that represents an action tied to that object. So in one case you would read out loud the word apple but in another you would have to come up with a verb such as for instance bite or eat. So what we're trying to do in this experiment is get at the fact that the brain is honoring this distinction between the ability to come up with words that correspond to nouns in fact common nouns and the ability to come up with words that correspond to verbs that correspond to actions in space time. The result of this experiment which is analyzed with a variety of very complex analysis both CDA which is developed by Mark Raichel and his group and Pat Brain Fox which is the one developed in our lab what it shows is really quite remarkable is that the generate task this task in which you generate a verb activates systematically a region which is contained here by the yellow contour and which is actually the region that corresponds to the area of damage in patients that have problems with generating with producing verbs. So we have now from two different methodologies one that uses lesions and produces a deficit and another that looks at the normal brain and asks for a task that corresponds to the one that is defective. We have now this very marvelous correspondence pointing to the same system. This by the way is one individual and this is the mapping of the activity in that particular individual during the during that task and it is shown on the 3D reconstruction and also shown in here in a coronal cut you see the slightly colored area that corresponds to the peaks of activity. Now we'll skip that and let me tell you another very quickly about another experiment also with Pat. This is an experiment that is ongoing and the analysis has only been done in eight of the subjects in which we ask the patients to produce naming again trying to probe with a different approach the kind of results that we have with lesions and we ask the patients to name known faces such as JFK as you saw the naming of animals or the name of manipulable objects. So there were three entirely separable conditions in which people had to produce the names to these different areas and of course the hypothesis which I'm not going to give you in detail because it requires a long story to give you the full rationale is that different systems will be handling these different processes and we have in fact quite a lot of results from lesion studies supporting the idea that manipulable objects are going to be handled largely by posterior systems on the left that the naming of animals is probably going to be a bilateral process and is more anterior in the temporal lobe and that the naming of faces is even more anterior. Well let me show you I'm going to ask you to concentrate on these three columns with colors one corresponding to the activity for faces another with the activity for animals another the activity for tools and these two slices the one on top and the one on the bottom correspond to those two levels those two blue lines that Hannah has run across that particular brain of a particular subject that is depicted there on the side and now I'm going to ask you to look intently at the color red which corresponds to the areas that on the average produce the peak activity and I'm also going to ask you to realize that the left side is on the right and the right is on the left. Now when you look at tools you realize that there the activity is maximal in the left hemisphere rather than on the left on the right and it is maximal actually in this region which corresponds to about this point which is exactly the place where with lesions we have seen problems with the naming of manipulable objects. Here we have the activity that corresponds to the animal naming task and it is remarkably different position from this one and for one thing it does not respect anymore the unilaterality of the process of manipulation and finally look at what happens with faces where the process is pushed forth into in fact the tip of the temporal lobe but remarkably on the right on the left and actually produces negative activities in the posterior regions. This is quite fascinating because in fact in another study that is being done by another colleague we have found that the activity that lesions in the anterior tip of the temporal lobe on the left are excellent to produce a loss of the ability to name unique individuals while preserving virtually everything else in terms of language capacities. So as a whole what you're seeing here is the possibility of these methodologies enlarging the scope of our knowledge about the brain at the level of large scale systems so that if you would now ask me about the map of language related areas instead of the Christmas cookie picture that I showed you at the beginning we would now have this much larger area that continues to enlarge. The thing to remember is that the area enlarges it corresponds to different systems but the different systems are made of several and separate components although they interact by fit forward and feedback connections. Now let me change gears and tell you about something which I would like to be the main topic of this of this conversation and which has to do with notions such as emotion and rationality and I would like to start that story by invoking an individual that many of you have heard about is a famous patient from the last century called Phineas P. Gage and this is a patient that probably would have been as well known as the patients of Paul Broker or Carl Wernicke had his doctor, John Harlow, been able to obtain an autopsy in the patient and been able to relate the problem that the patient had to a particular area of the brain. Unfortunately he didn't and all that was recovered of that patient was the skull and this year Hannah in her lab was able to produce a reconstruction of the possible passage the area of possible passage of the iron bar that destroyed one part of Gage's brain and therefore complete in a way obviously tentatively what John Harlow started. Now what John Harlow did was describe in 1868 pretty much at the same time that the first language related patients were being described. Described that this individual who was young, promising, socially adapted, very capable and responsible in his work had turned overnight into an individual that although for all intents and purposes he appeared to be able of body, able of language, able of intellect he was no longer able to have a sense of responsibility in terms of his work. He no longer could be trusted, not that he was criminal or anything like that, he just could not be trusted with the kind of responsible job that he had. He used profanity in front of people where before he had not and clearly something major had happened in his personality and something that quite particularly had to do with the ability to govern his life in a way that would be conducive to his betterment and consonant with the kinds of rules that society had taught him and the kinds of principles that one might call ethical principle. So this was what was lost in Gage. Now throughout the rest of the century and then in the 20th century other patients were described with similar conditions, this time now with some knowledge about the areas of brain that were damaged and the clear relation was established between frontal lobe structures and this kind of disturbance that would not cause a major intellectual loss but at the same time would render an individual incapable of steering his behavior in society. And the troublesome thing was that the analysis almost always yielded a great paradox. You had people that went overnight from being proper adapted individuals to being marginal and you also had at the same time an enormous preservation of the instruments of intellect so that when people struggle to find problems with language or memory or working memory or a logical capacity, ability to calculate attention and on and on, you generally came up with very little and the story has in fact come to our days with terms such as the enigma of frontal lobe behavior, a term that Hans Lukas Toiber, a famous neuropsychologist used, the mystery of frontal lobe functioning, people had not really had a handle on this. You certainly cannot explain these people's behaviors by something as narrow as a problem with logical disturbance or a disturbance of attention or of working memory. So let me tell you where we are right now and where we are is this. For one thing it appears now that the patients that have the closest to what one could call the gauge condition are patients that have damage in one particular sector of the frontal lobe rather than all of the frontal lobe and that sector happens to be the ventral medial. You're here looking at the brain from below and you're seeing one such patient and you see that the medial part, this is the medial part of the right hemisphere and here the medial part of the left is where the damage centers and when you plot many such patients, in this case there are four of our star patients with frontal lobe damage of this type, you get the idea of the systems that are most commonly involved. The other thing that is very obvious is that these individuals, that is not to be read by the way, don't worry I will walk you through it, these individuals have a remarkable history in the sense that for instance in this particular patient, this is a man that is very intelligent currently has an IQ of over 140, this is a patient that has been studied by my colleague Steven Anderson and this man has a very good education and he actually had a very good career up to the time in 1982 when he had a neurological event that produced a lesion of this type and what has happened after that is a whole catalog of catastrophes in personal and social terms, the professional activities can no longer be followed, the marriage and the relations to France fall apart and these individuals in spite of a remarkable intelligence are no longer able to guide their life in such a way that all of these marvelous relations that constitute our social fabric can be maintained and even in the personal realm where it concerns a spouse or children those fall apart, the sense of responsibility in a job falls apart and they cannot be counted on to continue working well and we end up in the situation of this person who by now has accumulated a lot of debt, is virtually isolated, has no job prospects whatsoever in spite of an IQ that reads over 140 and is in the genius range. Now to dramatize the level of dissociation we have here I cannot resist reading you a little passage from this from this patient's protocol to get you an idea of what it is to be a person who can no longer operate in society and constantly makes errors of judgment in relation to others and who in a task in which he is asked to produce what we call alternative thinking is asked to produce options of action for another person he comes up with the following responses so patient DV is asked the following hypothetical there is another person called Victor who wants people to listen to him but no one ever does what can Victor do to get listened to and you don't need to read that I'll read it to you here's the the responses that our patient who cannot navigate socially in real life and real time here's the response he gave to the to the question make sure that he wants the right kind of people to listen to him that is people who care for him he can learn to articulate what he's saying so he's not boring he can establish eye contact and become more animated so that he thinks what he's saying is important sometimes you can encourage people to listen to you if you are a good listener but other times people are pretty dense they just don't pick up on it he could write a note to those he cares about and say look I've really got to talk and what he seems to listen would you be willing to set aside some time just to listen to me I guess the thing I would say is learn how to be a friend yourself and you will attract the right kind of friends hopefully he could take a course like how to win friends and influence people he could develop a pamper and express thoughts in writing he could take a writing course at the university and on and on and what you have when you read through this response and there are many that he produces is a first-rate intelligence at work being able to come up with a very large collection of options that would be available to our hypothetical victor person who was not able to get friends to listen to him and what you're seeing is a dissociation again between the conserved knowledge that this man has about how one might act and his real time real life behavior where that knowledge is no longer applicable or applied in ways clearly does not follow it so it poses all sorts of questions that should make you think does a person who behave very wrongly in society do that because he wants to do that or do that because he doesn't have the knowledge to behave better well we don't know and it depends on the conditions and they have to be studied especially and in every each individual now the situation where we are right now is that we can see that these individuals do not have a problem of logical competence in any way shape or form and that after all is said and done what is most remarkable about these individuals in addition to their very abnormal behavior in real life is that they have a remarkable abnormal processing of emotion and feeling and that is something that was not always apparent to me but became apparent to me several years ago and it led me to a hypothesis which we have now been testing in our laboratory for quite some time and which is known as the somatic marker hypothesis in a nutshell what it concerns is this I have I raised the possibility that what is wrong in these individuals is the loss of a signal which is actually coming from their emotional and feeling process which allows or would have allowed them to mark a particular option and a particular consequence of an action as good or bad and what this really says in the broader context is this it is quite possible that the way we steer our behavior as adults and in fact as children too is not just by following knowledge charts and following a logical competence that would make us move from A to B to Z but rather using that logical competence after we have been pointed into the right part of the decision-making space by a signal that is very basic that is biologically based that is quite related to emotion and feeling and quite related to what emotion and feeling ultimately express which is biological regulation this is the hypothesis in a nutshell it is not by the way that we think with our emotions or that we decide with hunches and gut feelings it's more than that what I'm claiming is that if you lose the ability of having some hunches and gut feelings set you at the beginning of your reasoning process in the proper course you may never be able to get there but once you get the proper hunch you still need to use your deliberation you still need to use your knowledge and logic in order to get at the proper harbor that's the point in the hypothesis now let me just close by telling you about one experiment that we have done that relates to this particular topic many have been done in our lab and I'm going to describe you a task that was developed by a post-doctoral student of mine Antoine Beshara another brilliant Canadian and the test goes like this you have in front of you four decks of four decks of cards we call this a gambling text and the decks are marked A B C and D you also have in front of you as the player in other words the subject which can be a patient or a normal individual you also have a loan of money in this case two thousand dollars of play money and we're going to try to make this game very much like real life in which you know a little bit but you don't know everything and you're going to have to be governed by the discoveries you make about what could regulate that life and what we tell the subject is look you've got two thousand dollars we want you to play this game in a way such that you will minimize your losses and if possible maximize your gains we just don't want you to lose money and you're going to play the game by turning cards from any of the decks in whatever order you want will not tell you how many cards you have to turn and will not tell you the order and we'll tell you one more thing is that every time you turn the cards you're going to be given some money and at times when you turn the cards you may also be asked to pay some money and that's where our the knowledge stops we don't say anything else the game starts and the person starts taking cards well what happens is that unbeknownst to the player just like in life two of those decks are actually pretty good they happen to be decks c and d where every time you pull a card you get fifty dollars but every now and then you have to pay a penalty but the penalty is very low on the other hand there are these two decks a and d where every time you turn the card you get a hundred dollars but every now and then you get a penalty that makes you lose your shirt so you get you can run say four times on on deck a and all of a sudden you're told by the way you get a hundred dollars but now you pay me 750 or you pay me a thousand which is very different from the other so unbeknownst to the player if you're going to play on these two decks you're going to lose money but if you're going to play on these two you're going to make money and here's what normal individuals play like you have a normal controlled chart on top and this is very consistent and it's so amazing that it's actually consistent across cultures it's consistent across ages and education and even consistent across high risk takers and low risk takers is that after a while people realize that there's something the matter with the a and b decks and they move to the c and d and that's where they stay most of the time until after 100 card turn you say stop the person comes out ahead now look at the performance of one of our ventromedial frontal lobe patients the ones that have in real life such problems with rationality what you see something quite amazing is that they persist on going to the a and b decks and in fact they do very few choices from the c and d now there are many ways of interpreting this but let me tell you what's most important first of all first this is a task that for the first time allows us to detect and measure in a laboratory setting this kind of problem that had always eluded neuropsychological testing second it tells you that it may well be that these individuals are in fact being controlled by the present circumstances by the here and now and they are quite driven by in part the the lure of the high yields that those decks give the a and b but also at the same time by the inability to mark the bad scenario that inevitably will come out of choosing a and b because ultimately it should become clear after a while certainly after about 20 turns as in everybody else that you're going to lose money given the very high degree of penalties somehow incredibly intelligent people continue to play the game of in the bishara task the same way they play the game of life it's a game in which they're going to lose ultimately now let me tell you we can skip this this just plots the general profile of a typical control and of a patient and these these differences are remarkably significant but now let me tell you about something else that we did she's actually suggested by Hannah and which was the following since our basic interpretation is that this defect corresponds to a lack of an internal signal that would steer these people away from the bad decks and into the good ones we decided to look at to monitor skin conductors responses continuously while these individuals play the game and the very interesting thing is that these individuals do have good skin conductors responses as you can see here you have here for instance a control has brain damage but not in the frontal lobe and here we have the the skin conductors responses to a deep breath and to clamping in our patient DVR which is one of our well-known patients with this problem and you can see that the skin conductors responses are quite robust it are in fact indistinguishable from normal so we know that the apparatus to produce skin conductors is normal in these individuals with damage to the ventrometer frontal lobe now here's what happens when you monitor the performance over a long period in the card game we realize that in the period that precedes a choice and that corresponds to the patient thinking about the choice and then beginning to move out the hand towards the deck you start developing a progressively higher response of skin conductance and it turns out that it is for decks a and decks b the ones that are bad that you produce the highest skin conductance response in other words there is something being generated in the four seconds that precede the actual choice that is clearly physiological at that point that varies over time is related to the amount of experience the patient is getting and is in fact related to the negative experience and it is something that you might in fact interpret as a physiological signal that the brain is clearly sending to the body relative to the alarming nature of decks a and b relative to decks c and d which are the good decks now let me tell you what happens to the patients and now you have a comparison you have the top one which corresponds to the average of 19 controls and here you have target patients which at this measurement I think were five and what you see is that those patients are not generating any of the anticipatory responses the inevitable conclusion is that in fact contrary to the normal individuals there is no machinery of anticipation for this response and the patients are indistinguishable across all decks one little one little wrinkle in this which is a marvelous one is that we have now been interrupting the task early on and we ask the patient with subjects or the patients what is going on and it's quite obvious that by the time these first responses are emerging the subjects have no idea whatsoever that there are good decks and bad decks and they're still going through the process of sorting out what may be happening in other words it may well be that in advance of our conscious deliberate decision that some decks are good and some decks are bad in fact the brain is already responding to the repeated punishments by creating a signal in other words there is a biological machinery that is operating in advance of our cognizance that there is good and evil in the world okay let me close by showing you this image and it is an image of my idea at the moment of what it is to create a neurobiology of systems for emotion and feeling and it looks complicated but it's actually very simple up on top you have something that I've called the object you could conceive of that object as for instance a person that you really think is evil and that is really frightening the living daylights out of you or for instance a grizzly bear that you might encounter on a trip and what we believe happens in terms of the creation of emotion and feeling which we believe is so important for the generation of a decision process is in fact the processing of that let's say it's a visual object in early sensory courtesies and then the processing through higher order courtesies such that a lot of knowledge can be correlated with that object and all of that in my idea being represented in early sensory courtesies but then something happens which relates to the unique experience that each of us has had through the process of education and acculturation and which involves both prefrontal courtesies as well as a set of structures known collectively as the limbic system they include such structures as the amygdala the anterior cingulate cortex and the hypothalamus those structures by the way are those that are most active in the regulation of our survival processes you cannot have life without them they regulate the internal milieu they regulate the biochemical panorama of our bodies they also regulate our appetites and instincts our drives which ultimately are critical in order to maintain the survival of an individual or the species what we think happens is that as this processing is happening and this processing is by the way not just sequential but a bit more parallel than is represented here we then generate a set of responses that are marked at this level where i'm pointing now there are these four major lines of response and one goes to autonomic nuclei and can generate such things as a change in the heart rate or in the rhythm at which we breathe or in skin conductance and those are the things that have for millennia allowed us to sense that when we are emoting something changes in our body something in our viscera response to what is happening whether it be good or bad we also have changes that occur towards the motor system for instance using the basal ganglia and those allow us to change our posture to change our musculoskeletal arrangement such that we react with a certain body language to a particular object and then we also have responses that are endocrine and peptide you have loss of neuropeptides and hormones that are being sent not as a neural signal not through the nerves into the body but rather into the body out of the blood stream and change the way the body is operating and finally you have a set of responses that go towards neurotransmitter nuclei located in two areas that some of you may not have heard about but I call the brain stem and the basal forebrain and it is there that in small nuclei substances such as acetylcholine dopamine serotonin are being manufactured now let me take you to what this produces what this produces massively especially those three first boxes on the left is a change in the body as a result of the object the body is going to change and the entire landscape of how our body is is going to be different in the thousand milliseconds that follow our seeing a particular object and that is what I call the emotional body state incidentally a lot of this same idea was developed by William James at the end of the 19th century and it is an absolutely superb idea that unfortunately was not properly followed up by neurobiology during the 20th century now William James did not know about these responses here which are very important nor did he know about the pathways that we had to put this together now the fact is that out of the basal forebrain and the and the brain stem we can then respond also to all levels of the brain and modify the way those brain networks are operating and out of the body itself through a tremendous number of neural lines we can get to make the representation of the changed body state in the somatosensory cortex so in a nutshell what I think is happening and this is a perfectly testable hypothesis to the human brain and body in fact to the human organism when we emote is a concerted change in the body proper that gets to be represented as a particular picture if you want no difference in terms of cognition from the representing of one of the pictures that David you will talk to you about except that this one is in somatosensory cortices and it so happens that it is more the ones on the right hemisphere than the ones on the left but then on top of that there's also a new change that happens in many of these networks that are made to work at different speeds and with different deficiencies under the agency of many of those neurotransmitters that act on the same structures at the same time so there's a very complex package and it is this complex package of changes directed at the brain itself and directed at the body but represented back into the brain that I think constitutes the base of a feeling now I think that feelings are in fact what humans for millennia have considered the very core of their souls I think that feelings are part and parcel of the process of biological regulation it would be extremely unlikely that they would not have a major role to play in the steering of behavior they obviously do in in non-language animals and I think they do in humans as well and so the process of reason as we can now begin to carve it and fractionate it in neurobiological research of systems is not certainly like Descartes would have wanted it is not something that is born out of thought and it is not something that is born out of language it existed for long before in evolution and it existed very close to the regulation of life processes thank you very much thank you very much I'm tired it's a good work isn't it wonder and say it commentary from each of you before we do I have to answer just something brief I think Dr. Candel wants to speak hey Dr. Candel will start with the first question here the reason I think we're slow in formulating questions is that Tony has given us really so much to think about I'm still working to assimilate his view of the interaction between emotion and rationality in the execution of behavior and in speaking to David Hubel while we were both enjoying the talk several thoughts struck me which I thought that Tony might elaborate on first I think I'm right in saying that the area in the prefrontal cortex that was damaged in Phineas gauge and in several of your patients also is importantly involved in autonomic regulation and I wonder whether in simple terms one of the defects these patients might be suffering from is an inability to this is restating what you're saying because of this defect in the autonomic nervous system there might be a defect in the handling of feedback signals or even the ability to generate it so this is really a defect in the autonomic nervous system number one and in that context I wonder whether you would take us through the James Lang the cannon barred the Stanley Schachter and the demasio theory and point out to us the modern evolution of thinking about the biological base of emotion so to distinguish the various generational views of that it's a tall order another tall order David and I have had interesting questions today just the whole day to answer them no first with your your point about autonomic regulation it's by the way it's very interesting to think that there is really so much ignorance in our neurobiological knowledge and and for those in the audience that think that for instance everything would be known about the autonomic nervous system let me tell you that there's an area where there's tremendous lack of knowledge nobody has actually mapped all the pathways of of autonomic nervous system or for that matter of pain in the in the macaque monkey let alone the human so they're vast areas of ignorance that we still have but there's no question there are many centers that regulate and those are real centers that regulate the autonomic function the ventromedial is not a major autonomic regulator but clearly overrides so the way we see it is this critical autonomic regulators exist in hypothalamus in amygdala certainly in brainstem and then there are structures like for instance the cingulate or the ventromedial that probably have a control of higher order over those other structures so for instance ventromedial projects heavily to the amygdala has a feedback response and when you lose that control you're going to lose the ability to control for instance amygdala under certain circumstances because the the autonomic function is there very very well preserved it's just the circumstances that change and so under certain circumstances it cannot operate now getting back to to and as i showed in that slide the autonomic signal is perfect when it comes to a physiological response the the the story on james is very important and i i would like to start by saying that we've had a very long dark night for studies in emotion throughout the 20th century for reasons that i won't go into the beautiful work of william james of charles darwin and of freud were in fact leading us into something that would have become sooner the neurobiology of emotion and in fact the the biological perspective was there in darwin james had an organismic perspective that i think is beautiful and certainly freud was mining the the role of emotion in psychopathology but throughout the 20th century perhaps because emotion was seen as intangible and a nebulous not very uh objective affair the drive was towards so-called cognitive studies uh and then i think after the computer metaphor of mid-century this was became even more marked it is totally incomprehensible to me why people to this day separate studies in studies of cognition and emotion as if we could have cognition without emotion which is clearly absurd but that's the state of affairs so there was a long gap now part of the gap but certainly um canon and bard and and stan schachter true but there was not the the the influence certainly in in mainstream neuroscience the influence minimal there has been no symposium on emotion at the society for neuroscience for 15 years that ought to tell us something um what i think happens to just to go back to james is that he had a beautiful idea the idea suffered from several shortcomings one he made the body component of the loop a necessity he did not uh admit that they the body could be bypassed like for instance in my full theory or hypothesis i prefer to call it the body can be bypassed because the body can be symbolized so we have what i call the the body loop and the as if loop so after a while uh the the brain can learn to generate a simulation of the body state avoiding the highly uneconomic loop through the body and using the very slow autonomic nervous system to generate changes this is something that james never thought about and most of the criticism in james against james was directed at that lack people did not want to admit that the thing always had to involve the body although we all know from our experience that in fact a lot of the time emotion does involve a body change the second thing and probably the most uh problematic was that james did not think about anything but what i now call primary emotion he thought about emotions that would be the kind of response that you have to the grizzly bear which are totally dispositional inherited uh available prior to learning and development and those responses would appear without any kind of evaluation on the part of the subject so you see the thing and you'll get a response now it's perfectly obvious that in most circumstances we react with emotions especially when we're dealing with complex emotions that relate to our social and personal affairs we react with an emotion filtered by an evaluation that is critically tied to the way we have developed as individuals and to our knowledge and to the dicta of the society we live in and that's what james had no allowance for and i don't think he should be criticized for that because it was a beautiful beginning but he was just hammered on the necessity of the body loop and on the lack of an evaluation and clearly the only thing that has really evolved i think in this century is the notion that there is an evaluation that is needed a lot of the time although not all the time that's how i would put it just briefly church um yeah i'm gonna try to make this as brief as i can um one of the things that we are advised to do as we grow up and one of the things we advise our children to do is to learn self-control so and the model that of that that's usually presented is that we want to have reason controlling emotion that that you can see what or understand what a certain course of action requires and even though you may feel fearful or you may feel abhorrent or whatever that reason requires that you do it um now i foresee some changes in in that ideal given what you've said but how do you understand the process then of of acquiring self-control so that the the the heart doesn't always rule the head the i think it's a process that that i really describe as that of of secondary emotion it's a process in which you can uh you you can harness your responses and you can adapt them to to uh to especially to to social and cultural controls um it is something that you can probably do i i i don't think i know exactly how one achieves that i i i never thought about the about the process but it's a process that is not unlike that of habituation and desensitization uh by probably by repetition uh of uh of the of the of the situation but it's certainly a very critical process and i think that the again the the big difference is that the primary emotions are sort of a stock that we have a set of dispositions that that are probably species specific and that will come into play pretty much given the same situation whereas the secondary emotions are culturally uh bound and will come into play very much depending on what the development of an individual has been like there's an enormous room for variation in that all we need to do is look at the different cultures uh in what they in fact allow in terms of expression of emotion dr bjergling yeah i would like just briefly to come back to an issue that was brought up this morning that is the binding problem and i'm thinking of your description of elements in the temple though being able to act to identify faces for example um and that neurons deep in the temple though in fact may be responsive uniquely to such elements in the picture now we heard from david ugl's presentation that the visual image is not basically processed in that way it's uh parallely divided up into elements and how come then that a specialized area can have such a unique function with respect to the components of the visual picture when it's not processed in that way do you see this as a problem when it comes to tying anatomy to processing in the brain or would you uh could you comment this could you see on a good anatomical substrate no i i i i don't see it as a problem at all i think that for is if you look at the architecture that for is the connection of anatomists have been putting together for us uh leading all the way from primary courtesies into the vast expansion of the early sensory courtesies very similarly in visual or auditory systems and then the convergence through different hierarchies towards what i would call epical points such as the interior temporal lobe the entorhinal cortex or certain apices that are located in in frontal lobe what you see actually is that because of the recursive nature of the architecture because of the fact that you always project forward but you reciprocate backward you can maintain a a dialogue across the entire hierarchy not to mention the heterarchical connections now the way i see for instance an interior temporal region that's a will light up quote unquote in a pet scan uh in relation to faces it's not that that region contains those faces represented there on the contrary what that region does is be activated because it will connect and make linkages between many many parts that are in earlier courtesies that when properly activated will define say your particular face in a particular context so i think that the only place in the brain quote unquote where you have coherent images is not one area but actually a collection of early sensory areas i do not believe that those images are ever transferred down the pike into another area what i think there are is linkages and in a way what the interior temporal lobe structures of frontal are doing is holding the capacity to activate back such that you reconstitute on the moment on the fly as it were a particular image but you don't have those images up front and i think that we can say that with some confidence because we know the result of lesions in interior temporal lobe structures and we know that the people that have those lesions have not lost the ability to generate the most beautiful images in the world it's just that they have lost the ability to relate those images to proper previous knowledge so it really has to do with the basic conception that we we use for the brain if we're going to conceive of the brain as in the traditional terms of a sequence of processors that ends up in the interior parts of the brain be them temporal or frontal with the gorgeous cinemascope pictures we're going to be in trouble because there's no such things as those pictures in the brain in all likelihood but if we if we go through the almost absurd view at first hand that in fact the place where you have the pictures when you see is the place where you're going to have all pictures when you recall them which a lot of cognitive neuropsychology is now pointing to then i think we'll be in better in better terms but you can want to interpret this such that a picture can actually be stored in the brain so that we can for example recall it if we i think what you start of our okay a face we know well we can see it in front of us which represents a degree of okay what it means that the picture is never assembled in one place okay shouldn't understand it but right understood what i think happens is that you have the potential for the reconstruction what i think we have is the recipe for the reconstruction of a face or anything else that you know well so you are on the moment you go out of that you could call it coding and you come back and you re-enact activities in the brain that are similar though perhaps not quite equal to the activities that once happened during perception so i think recall is nothing but an attempt at replicating the process of perception and that's the reason why we don't recall as perfectly as we perceive but it is a process of reconstruction and the image that you get in the recalled picture when if i now ask you to think about your house in lund uh you're going to come up with a picture it's not as vivid as your perception of it but it will be a picture and it has coherence as much as it does in in perception but it's going to be recalled on a moment and if your house changes if you do an addition on it ten years from now you're going to recall another picture that will include that addition but it's all reconstructed i don't believe that you have files with pictures with polaroids stuck into your brain that you can pull out like you do from the from the filing cabinet that's the big difference okay we're gonna there are a number of questions that were provoked that asked about criminals and criminal behavior i think i'm going to read two or three of them just to give you a flavor and then ask you to respond maybe to a central question i understand that dr churchland may be raising questions that have to do with responsibility so we probably won't move away from this topic too far but these are questions that have come from the audience has there been any study done on criminal behavior using pat for localization of possible lesions common to this behavior your presentation suggests that many asocial behaviors may be related to the ventral medial frontal defect or damage are our prisons jails institutions holding tank for people with these brain problems this may be more philosophical than scientific but given the influence of your as a nation event ventral medial dysfunction how might that influence the civilized response to criminality in other words i can we write criminals off as largely biological phenomenon all of these seem to be asking essentially have you found an area in the brain that predicts asocial behavior in a very general way and of course that could raise the specter of could we use this in a predictive diagnostic fashion can you tell us something about the limitations of diagnosis with respect to this as you can imagine this is an incredibly complex subject and you can cannot do justice to it with with bullets with just one you know one liners however certain things that i i definitely want to make clear one is that the kind of individuals that we're describing normally did not have what we would call criminal behavior this is very important for you to realize nor did for instance poor old phineas gauge have criminal behavior as such now we think that they don't because these are individuals that have in fact had a normal process not only of brain maturation but also of education and socialization so all of these individuals have had the onset of their brain damage late in life at least as adults and therefore they can rely on a previous structure and on a lot of knowledge that certainly curves the worst of those impulses it doesn't mean though that there are not conditions in which they can be criminal behavior in fact we have now started some cases which are a variant of these but not equal in which people do have criminal behavior and in fact it can be traced to a system the second thing is that there's no no one area we're talking about a complex system and as anything in neurobiology you have to understand it in terms of levels their molecular levels their their cellular synaptic circuitries they're the neurotransmitters that work at those circuitries then you have larger scale systems and then you have the relation to a social environment in which those individuals have lived so any attempt by anybody to try to reduce criminal behavior to something as simple as a gene or a transmitter as serotonin or a hole in the brain is of course very dangerous and certainly wrong you have to understand it all all these multiple levels and you have to understand that all of these factors can be brought to bear i'm perfectly convinced that there are individuals that have abnormal behavior and criminal behavior because of many of these causes some genetic factors some factors that are neurobiological and were acquired like for instance an infection at birth or a stroke or encephalitis or what have you all of that is true but there are also individuals that i'm ready to believe have criminal behavior because of social circumstances in which they are inserted so let's not have easy way out in this and think that everything from the social environment to the genome can have an influence and that's exactly how it should when we think that this is some of the most complex behaviors that you can deal with that the exact proportions in the interplay are something to be sorted out by appropriate research however there's no such research yet i would just make one point that is sociocultural is that i am not aware that people want to study the problem of criminality and violence from a point of view of science and very often you resort to political issues into political solutions it really doesn't pay to incarcerate people or kill them if you don't understand the causes of criminal behavior and of violence and those problems are certainly amenable to research if you just have the appropriate attitude i think okay thank you very much we would like to inform you that there'll be coffee and cookies on the mall eckman mall outside in the main area of the college and welcome you back for our 330 talk with dr churchland thank you very much