rate increases, our palms begin to sweat and only then has a response to the fact that we're in the state of pan doing we have the conscious feeling of emotion. >> rose: the eighth episode of the charlie rose brain series underwritten by the simons foundation coming up. captioning sponsored by rose communications >> rose: tonight we continue our exploration of the wonders of the human brain. we rush this evening to the subject of emotion. emotions are a critical part of the human experience. they add color to our mental lives, they exert powerful control over our behavior. when faced with a tough decision we rely on our emotions somewhat to help guide us. last month, we talked about positive emotions such as reward and pleasure. tonight we turn to fear and anxiety. human have evolved to feel fear in response to danger and to exhibit aggression when threatened. today fear and aggression can be found throughout the animal kingdom. by studying these emotions in animals, we may one day learn how to control violent behavior in ourselves. last month we discussed how the brap's pleasure circuits are corrupted by addiction. this evening we will learn how the brain's fear circuits go awry in clinical syndromes of fear such as chronic anxiety and post-traumatic stress disorder. human anxiety disorders are some of the most common mental illnesss in the country. nearly one-third of all americans will exhibit symptoms of an anxiety disorder at least once during his or her lifetime. post-traumatic stress disorder's also becoming more prevalent. more than 40,000 war veterans are currently affected by this illness with thousands more cases going unreported. thankfully, progress has been made in understanding the biology of these diseases. tonight we will discuss several potential therapies that could one day offer hope for a cure. joining me now is some of the world's leading researchers into the study of emotion. antonio damasio, his work has helped us understand emotion, decision making, social behavior and even consciousness. he is a professor of neuroscience at the university of southern california and the director of the brain and creativity institute. he's also the author of several books including "descarte era and looking for spinoza." joseph ledoux. in the 1970s he revolutionized his field by showing emotions could be studied in animals. he's a university professor at new york university and director of the emotional brain labs at the nathan klein institute. he's also the author of the books "the emotional brain" and synaptic self." kerry ressler. he studies the genetics and neurobiology of post-traumatic stress disorder focusing on the interaction between genes and environment. he is a professor at emory university. david anderson. he studies the neural circuits that control fear and anxiety. he is a professor of neuroscience at cal tech and a howard hughes medical investigator. and once again, my co-host is dr. eric kandel. as you know by now, he's a nobel laureate and professor at columbia university and a howard hughes medical investigator. he is, as you know, the mastermind behind this program and once again i'm pleased to have him here at this table to tell me what we're going to talk about this evening. welcome. >> thank you. pleasure to be here. >> rose: where are we going tonight? >> we're going to discuss emotions some more. emotions are feeling states that enrich our mental life. they lead us to seek out pleasure and to avoid pain and tonight we're going to begin by discussing fear and anxiety states and then go on to discuss aggression. >> rose: why are they important to our survival? >> in the presence of a danger, the most important thing is to get away, to freeze, to decide, you know, what sort of action to take and to take that action. this is more important than almost anything else for survival is to know what is predator and what is prey. >> rose: once again, you have brought with you a book. what did william james tell us? >> when we talk about fear, we're speaking about an emotional response to a potentially threatening event in our life. so if a growling bear were to come into this studio right now and attack the two of us like that... >> rose: (laughs) >> ...we would be frightened and we would respond with an autonot no, ma'am i can discharge. our heart rates would increase, our respiration would increase, we would sweat, we would feel very frightened. how do we think about this? this is the guy that got us to think about this. in this book he made two major contributions. one is he took psychology and helped separate it as a distinct discipline different from philosophy. he removed it from philosophy, number one. and number two, he tied it into brain science which is what this program is about. and he has many diagrams here that show how a variety of mental functions can be localized. and he did this in 1890 knowing much less than we know today. and he posed the really great question in emotion and that is what determines the sequence? when we see a bear coming in here and we feel frightened and have this autonomic discharge, what comes first? the feeling of fear? the terror? and only later to do we feel the changes in our body. >> rose: let me guess, the bodily changes come first and we feel the fear. >> no wonder you're in charge of this program. that's exactly right. and that insight that the... the feeling state, the conscious perception of it is, in fact, a reaction to the bodily state, has set the agenda for everything else in the study of fear. for example people began to ask what is the neural circuit that mediates these two processes, emotion and the feeling state. and because we can study the emotion part not only in people but experimental animals, we have a very good understanding of the neural circuitry of fear better than any other emotion. >> rose: so we can learn about emotions and humans from studying animals? >> absolutely. it turns out the neural circuitry for emotions, not the feeling states which we can't study very effectively in animals, for emotions is very similar in people and experimental animals and in both cases involves critically the amygdala and region deep in the brain that orchestrates emotion. so we can study that rats and mice and joe ledoux has pioneered this study. in addition now that we have animal models for anxiety states we can also begin to get some insights into the disease processes that fear is recruited for. and we know they fall into two general categories and kerry ressler studied this extensively. one are chronic anxiety states that are related to depression and they respond very effectively to antidepressants medication. but another class based on panic attacks, sudden feelings of intense fear and this includes phobias and post-traumatic stress disorders and these respond to other kinds of therapeutic interventions. >> rose: and then there is aggression. >> there is, indeed, aggression. >> rose: and violence. >> and violence. and william james again pointed out to us that aggression has been with us since dawn of humankind people have been getting involved in warfare since the history of mankind. so the issue of aggression is built into the capability of human action. we need to understand the biological underpinnings of it and we need to understand how to manage it, how to control it. and one of the key question which is we will consider is to what degree is aggression determined by genes and to what dey it determined by behavior, by environmental experience, by interaction with other people? and what can we do to regulate and limit aggression except when it's absolutely necessary. >> rose: as we said? the beginning we have assembled, again, a remarkable group of people who have made it their life's work to focus on the braiand emotion. tonight, negative emotions. >> emotions can be categorized along the axis of pleasant versus unpleasant which is sometimes called the valence of the emotion and how arousing are they. so you can have a negative emotion which is highly arousing like rage and a negative emotion which is a low-level of arousal like sadness. and today we're going to focus mainly on those negative emotions that have a high level of arousal associated with them like fear and aggression or anger. now, these very old and powerful emotions. they're essential for the survival of animal species and arguably they have a stronger influence on us perhaps in our day to day lives than the positive emotions. it's often said that bad news sells more newspaper than good news. perhaps that is related to that in some way. so darwin was really the first person to focus in on studying emotions in man and in animals in parallel. and he wrote a marvelous treatise in 1872 called "on the expression of the emotions in man and animals." and what darwin showed is that the same emotions that are present in people can also be studied in animals. in dogs, in cats. in fact, darwin believed that emotions were characteristic and present throughout the animal kingdom. now a very important point is there there are really cotwo components of emotion. there's the subjective internal experience of an emotion that we have and that's what antonio has referred to as the feeling aspect of emotion and that's really a subjective state that we can only really study in humans. but what darwin and others realizes is that in animals you can study the outward behavioral expression of emotion. and what antonio has stressed is that this is what we mean in science when we use the word "emotion." it's the observable behavioral expression of emotion not the internal feeling state. >> so we see something and we run. >> that's right. >> rose: that's the emotion. >> and what darwin showed is that the expression of emotions like fear in humans and in animals are extremely similar and that they are conserved in evolution comparing what a cat shows on its face to what a human shows on its face when it's afraid. a very profound observation. now, darwin even believed that you could study emotion in insects. he wrote a wonderful sentence. he said even insects express love, terror, jealousy by their strij lags. and insects have actually been extremely important to biology in helping us to understand join gene. because insects are where we first learned about the relationship between genes and chromosomes. so as shown on the visual, thomas hunt morgan used the vinegar fly to show that genes are arranged in a linear sequence on chromosomes. we now know that genes are made of d.n.a. that beautiful double helix structure discovered by watson and crick. and what seymour benzer did in the '60s is he took this wealth of genetics in the fly and showed that you could use it to study how genes control simple behaviors like attraction to light. >> this was the first time one had a genetic handle on various behaviors. >> right. so it turns out you can study emotion like behavioral expression in flies just like other animals. so the two most common expressions of fear are freezing and running or flight. and so as we can see in this this this video, flies show a freezing like reaction when they're confronted by a dangerous stimulus, in this case the wind which could threaten to blow them away. they freeze, now whether they are experiencing some internal state we can't say. they may just be clinging on for dear life or they may have something more complicated going on but we can study this behavioral expression. >> rose: antonio, tell us about fear in human beings. >> i don't do insects. (laughter) >> rose: but you learn from insects. >> absolutely. it's very exciting and there's things i want to learn with this approach. so when we talk about fear in humans it could be in a dark street at night and suddenly there's a shadow looming over you or off car coming at high speed. that's the kind of stimulus william james identified and that's going to triger what i like to call a program of actions. it's very important to know the program is unconsciously processed. so you may become aware at some point that it is unfolding. that basically you don't need to know and your brain is going to execute a response of fear even if you are not fully aware of what is happening which is very stranges you because it may help you run away and seek a safe place. >> rose: you act before you know? >> exactly. this program is automatic. so it's part of your stock when you are born. now we've talked about musculoskeletal responses. your face changes, the you assume a mask of fear. the posture in the body changes so you startle and you can become more ridge jit in your position. but this is not full extent of it. within your internal organs, for example in the heart, your heart rate will increase. your get can contract. yours reseparation cycles become faster. these are actions being taken in concert. they're being executed as a program. finally the action that i really endocrine. so you have the secretion of a hormone, for example what happens with the secretion of cortisol which is going to change the state of your body and you have these two very typical specific behaviors and it's an either/or situation. you either freeze or run away. so you either freeze in place or you run away from the source of danger. now, the very important thing to realize is that these actions are changing the body and because of the signaling that the body can send back to the brain into different places from the parts of the brain where the emotion started you're going to get the full portrait of what is happening in the body at that precise time. and it's that portrayal of how the body changed together with the fact that there was a certain cause for the notion is going to give you the feeling of emotion. exactly what david was talking about when he talked about the subjective experience of emotion in relation to fear there's one critical structure that you have already talked about here in the previous program, which is the amygdala. that that's an orchestrator of responses. a broker. it's a set of nuclei in the depth of the temporal lobe and the amygdala can get signals from vision, for example, or from hearing and will generate a certain set of responses. and the responses will go especially to the hyperthalamus and to the brain stem. so these are different sites of the brain and in these difference sites you're going to get responses that include, for example the secretion of cortisol as well as the actual manipulation of the movement. so, for example, when you laugh or cry when you're having an emotion the program that is executing that is not the amygdala it's in the brain stem. now, where you're going to get the picture quote/unquote of what is happening in the body is in the part of the brain called the insular cortex. it's really a little island, as the name indicates, of cortex that is buried in the depth of both frontal and parietal lobe and there off representation of what the going on in your viscera, in your muscles, what is going on in terms of your bloodstream, chemistries. all of that is going to be represented and that will give you the feeling. that is the highest point at where you can... >> this is a terrific discovery which antonio contributed also very importantly and that is this provided a logical basis for understanding the idea that james is talking about. and this is that we have this bodily response and then we become consciously aware. insulin is a translating structure that brings this to conscious awareness. >> exactly. we have one very important part of the frontal lobe, the ventral pre-frontal cortex which actually is another trigger point just like the amygdala is very important for triggering fear and anger the ventral pre-frontal cortex is important to triger what we call moral emotions. emotions, for example, such as moral indignation or compassion or embarrassment or shame. and finally there's another region of the pre-frontal cortex which actually can modulate the emotions and here's the point at which your own volition, your will can impose itself on the way the emotion is being carried out. so you have some way of modulating the emotion. >> have we learned anything from animals in terms of emotion? >> we do have ways of studying in this great deal detail in both animals and humans and it involves using a simple technique that comes back to pavlov, the great russian physiologist who turns out to have been a great psychologist because he invented an approach called classical... which is called pavlovian condition. he's famous for his dog that salivated when the caretaker came in the room and so pavlov said let's design an experiment so he rang the bell and gave the dog something to eat so the next time he rang the bell the dog salivated. so the brain is able to detect these kinds of events like the association of the food with the arrival of the caretaker or the bell and on the basis of that association is able to then generate an anticipatory response. but we've been able to take this into the study of fear as well and eric's pioneering work was one of the great examples of this. so you're taking this into... >> rose: whole range of things about human emotion we learn from watching animals? >> we do. especially how the brain comes about to have a fear response or what we sometimes call a fight-flight response. in the case of pavlovian conditioning or what we call pav loanian fear conditioning, enough rat and give him a tone. and nothing happens when he hears the tone so he ignores it or if he gets a shock he'll jump and flinch but nothing much happens but if you put the tone and the shock together then on the right side the next time he hears the tone-- say the next day or two weeks later or a year later-- he'll have a fear response. he'll freeze, his blood pressure and heart rate will go up, hormones will be released as antonio was talking about. and this create what is we call the fear response. and it's simply that association or connection between the tone and the shock in the brain that allow this is to happen. so how does that happen? well, there's a part of the brain that we heard about and somehow the stimulus gets to the amygdala, activates a representation of danger and on the base thys responses come flying out. these are these automatic hard wired physiological and behavioral responses like freezing, changes in blood pressure and heart rate, release of stress hormones. >> rose: >> in fact we know more about the biology of fear than any other emotion and we know more about the disorders of fear, as kerry ressler has done, than any other psychiatric disorder. >> and what a number of imaging studies have shown when we actualally is what is wrong with the brain in anxiety disorders and fear-related disorders it seems the amygdala is one of the hot spots of the brain activated in these human patients. and so what we can think about there is that the disorders of anxiety and fear make up the classes of disorders where fear seems to be out of control. and there are anxiety-related disorders and these we cluster together in a group called generalized anxiety disorder. this is chronic disorders made up of worry and guilt, highly co-morbid with depression, very hard to separate from depression. the second class of disorders is fear-related disorders. and what what's particularly excited about this is thinking in this way is only relatively new in the last couple decades in psychiatry in part because of the work by people like joe ledoux and others focusing on the biology of fear and what we're realizing is a number of disorders that have been recognized as syndrome for many years-- panic disorder, phone i can't say, fear of heights, fear of public speaking, and post-traumatic stress disorder-- can really all be clustered together based on the similarities of panic attacks or fear-related attacks in these disorders. so if we focus then on what is a panic attack and what combines these disorders clinically dpshgs you see someone who's had a panic attack they'll say "i couldn't catch my breath, my heart was beating, my stomach... i thought i was going to die." so what it seems to be is that it's this whole hard wired fear reflex that's been so nicely explained here but it seems to be out of control. whereas you have this cognitive interpretation of these symptoms laid on top of it sechlt so that's what seems to tie the fear-related disorders together in a way that's different from anxiety disorders and allow us to focus on how they work differently. >> rose: what's the difference between, say, healthy anxiety and a negative anxiety. >> thank you for bringing that up. what we're talking about, fear, is something everybody can understand. >> it's essential for survival. >> what seems to be different is a functional definition of people who are unage to function normally because of their fear. that's where it becomes a diagnosis. we have a lot of measures and criteria but basically it boils down to are you able to function through it or not? so for example many people of phobias, you may be afraid of spiders but for the most part in modern day cities you don't have to avoid spiders and it doesn't come to the forefront of clinical recognition. whereas if you have a fear of heights and you work on the 12th floor. >> rose: or you don't want to leave your house. >> or can't fly, etc. and with post-traumatic stress disorder not only do they have intrusive thoughts like intrusive memories, intrusive nightmares, cues, they may have the startle response, the fear response not being sure what it is but it's the concept of avoidance where there there's a patient i've seen who was attacked in a dark alley and initially it was just dangerous to go out at night but after a while she not only wanted... didn't want to go out at night she was afraid of men, she couldn't be around that part of town, she before long couldn't leave her house, couldn't leave her bedroom. the world get mrs. and more dangerous and avoidance becomes part of it. so we can summarize that fear disorders are once in which this natural fear reaction has gotten out of control. so the other part i wanted to mention that i think is so exciting is why after a trauma, for example, or a fearful experience do some people go on to develop post-traumatic stress disorder and other people not? turns out after a severe trauma about 20% of people go on to develop the disorder and about 80% recover just fine. there are two primary classes that i think interesting. one is early development. we know early childhood trauma seems to affect the brain in a different way than in adulthood and those are at a much higher risk in adulthood if you have f they have an adult trauma for developing p.t.s.d. second is genetics. those who... a number of twin studies and others have suggested those who develop p.t.s.d. after an adult trauma are about 30% more likely to have done that based on genetic hartability. >> rose: along the road in the future we'll be able to do something about that? >> so there's two prongs for which that's important. one is if we knew which genes put one at a particularly high risk you could, for example, in the battlefield or the emergency room... >> rose: >> screen people ahead of time. >> rose: i see, screening so they won't be in that situation? >> right, you have them do other things in the service besides go to ttle >> or immediately after a trauma you can predict who needs more intensive therapy. and we hope by working with animal models by understanding what where the genes are acting in the brain that would give us new ideas into the biology and new insights into therapy. >> i think another thing that is emerging from these studies is how the genetics and the environmental experiences interact and the wonderful thing is because of the fit between animal models and people one can study how these occur and how does one learn to acquire fear. how does learned fear occur? >> as kerry was talking about in p.t.s.d., that's an experience that you have in the world and store for the rain as a result of the events that are occurring. so how do we put all that together and that's been one of the things we've been able to use animal models to explore in great detail. as we were talking about the amygdala as the clearing house for these responses, you talk about the clearing responses throughout the amygdala but it's funneled through which all the sensory information in the world is being controlled there. so a sound of the outside world goes into a part of the brain called the thalamus which i think you talked about in previous shows which is a gateway to the cortex shown on the top, the auditory cortex. but one of the discoveries in the 1980s is that the thalamus also goes directly into the amygdala. that means by the time the auditory stimulus is reaching the amygdala and activating those fear responses, it hasn't even begun to have its impact on the cortex yet. >> what i like about this finding which joe came up with, it really explains the james insight. off direct pathway that gives you the immediate emotional response and then you have an indirect pathway to the cerebral cortex that allows you to contemplate and think about it and have the conscious sense of it. the feeling state. >> the direct pathway is quick and dirty. gets there fast but not very precise. a bomb goes off in the room, we don't know what it is, it's already made us freeze and start to run away and stuff. by the time it gets to the cortex you only size the sound and the quality and all of that. but by that time your amygdala's already kicked in and got you out of the room. >> rose: do you develop a fear of insects and snakes? what causes you to have anxiety about those two creatures? >> you have it from the get-go. >> rose: you're born with it? >> you're born with it with. >> rose: your ancestors. it's jeanette snick >> because it would be extremely stranges you to have fear in relation to certain creatures, in relation to certain situations. same thing as the fear of lightning. fear of the noise of thunderstorms. and those are situations in which you have to protect yourself. whether it is an animal that can be dangerous or a physical situation in the environment. >> a rat is afraid of cats. >> rose: (laughs) that's great. yes. but let me come to one other point before i do this. we know stories of heroism on the battlefield. >> yes. >> rose: in which someone goes and does something instantaneous now they do it out of duty, out of love for their comrade? >> in part. you can't actually generate the responses so fast that you can proceed in a very heroic manner even if only midway through it you realize what you're doing. one thing that helps, i mention that parts of the brain stem which is orchestrating either the freezing behavior or the running away behavior, it so happens if you're running away from a danger as buck in a situation and say a war theater where you have to help a comrade... even if you're wounded you will actually not feel the pain because at the same time the brain is going to spritz a bit of an opioid into the spinal cord so that you will not feel pain for a certain period of time. so this is perfectly prepared in a certain response, you can study this in a monkey, for example. and the kind of anesthesia you get, it's as if you ask a doctor right then "give me a shot and let me have no pain while i do this job." so, in fact, our hero is being helped by our own physiology >> by our brain releasing certain kinds of chemicals? >> exactly. >> rose: including adrenaline that helps you lift up something you never realized you have the weight to do >> and i think another point is the great courage that courage is not lack of fear but acting in the face of it. >> rose: exactly. that's a great quote. >> feel the fear, do it anyway. >> rose: that's the idea, yes. >> if you have grown up in an environment where you have also been taught to exploit those responses in a positive way then you can, for example, war theater and many other situations you can act much better. because you can rely on that behavior... >> part of the training of the military. >> and we understand a fair amount about how learning occurs in this system. >> we never got to that so maybe we can get to that. (laughter) >> the key thing is if you're going to learn about a tone and a shock, there has to be a place in the brain where the tone and shock meet. it's not just a place but they have to meet on the same cell because unless there's a cell that can put the tone and shock together and store that relationship, the learning can't take place. and eric has beautifully shown this. now we've taken the model into the more complex rat brain. the tone is going to come into a cell in the literal amygdala, which is a key part of the brain for fear and the shock is going to come into that same cell and the shock is going to change ensooichls in that cell and cause those enzymes to activate the nuke lease of the cell to generate the genes in the cell nuke lease will generate proteins and those proteins will go back to the synapse where the tone is coming in and allow that tone to activate the cell in a way that it couldn't do before. >> more strongly than it did before. >> more strongly than it did before. and part of that may involve growth processes and so forth. but the key thing is that the auditory tone can activate the cell after conditioning in a way it couldn't before so the information can go from the late ral nuke las, which is the centry gate way into the central nucleus which is the motor output. so two parts of the amygdala are really important, the lateral nucleus receives the input, central knew leius is the output to the brain stem to control those responses. because those two are different you can imagine have people have pathological fear for two different reasons. some people may be overly sensitive. their amygdalas learn to be extra sensitive so they respond to other things people don't or the lateral amigtd la may respond in the same amount of threat but the central amygdala is hyperresponsive and you want to treat those people differently if they're overly reactive >> this is very beautiful work because it gives you a handle on these kinds of response which is you can find in patients. the people in are oversensitive to the world are the people that are not terribly oversensitive but respond too much. >> one of the things terry has done is worked with animals and people. he's a psychiatrist, he doesn't look like one but he is a psychiatrist. (laughter) >> well, you do. >> so several points to make, i think, along these lines, we've talked a lot about the hyperactivation of the amygdala in fear-related disorders. and if you treat them what happens and if you do imaging studies and look at how someone's brain responds before before treatment, it turns out that our two main classes of treatments currently and we'll talk about future ideas in a minute are medication and psychotherapy. both of these approaches decrease amygdala activity. and so the medications primarily being used are the classic antidepressants medicines that people are currently in that kind of lexicon, the prozacs and zolofts and those things. those things tend toward best with a generalized anxiety disorders the worry, the guilt, things associates with depression. they worked for about 50% to 70% of the people with general anxiety disorder bus they don't work nearly as well for the specific fear-related disorders like phobia and panic disorder and post-traumatic stress disorder. for the fear-related disorders psychotherapy seems to be much better. so aaron beck a number of years ago identified a host of cognitive behavior treatments. showing that exposure therapy tends to work particularly well and people with fear-related disorders. and exposure therapy is enter where we teach the brain to no longer be afraid. in a rat model if we did what we call extinction of fear, again, the same pavlov, who coined the term extinction over a hundred years ago. he would take the dog afraid of a cue or a dog salivated and give them the cue over and over again in the absence of the reinforcer, whether it's the positive thing or negative thing. >> rose: and they lost the here? >> they appear to lose it. >> rose: loss of physical reaction. >> exactly. and we think that by exposing the vietnam rhett ran to their memories of the fear and trauma, exposing the phobic patient to the tarantula or the snake, exposing the fear of public speaking person to give public speeches, doing this a few times is sometimes not enough. and sometimes it can exacerbate the anxiety. but if you do it enough the proper way with exposure therapy you extinguish or inhibit that fear over time. so that's where we are currently and we'd like to take a lot of the advances that joe has talked about and where we utilize the understanding of the neurobiology of learning and enhance the specific learning that goes nonexposure therapy. and so one sort of approach that's being done now is this idea of you don't have to expose yourself to the real world, you can expose it virtually. so this one particular visual shows a virtual fear of heights. and in this case it's very difficult to take your fear of heights patients and take them down the glass elevator and go up and down with them 100 times and it's easier if you can have them virtually in your office wear these helmets and it works almost as well. >> i think there are several interesting issues that emerge here. many people think psychotherapy is deep insight psychotherapy. it turns out from aaron beck on a number of people have developed psychotherapies that are behavioral therapies that are designed not necessarily to tell you how your mother and father affected you but how the adjust yourself to the here and now. and the other is a very creative combination of drugs and behavioral therapy. >> we'd like to erase the memories entirely. >> one of the things we found recently is memories become unstable when they're retrieve sod you have a memory in your brap, take it out, recall the memory or reexpose a rat to the fear stimulus and he act ace frayed again. that destabilize it is memory momentarily for several hours and if during that time you alter storage processes in the brain, either behaviorly or with drug it is memory doesn't go back in properly and is erased, removed, made inaccessible, we don't know what happens to it but from the point of view of the rat he's no longer afraid. from the point of view of the patient, they possibly could be better as a result with fewer emotional responses afterwards. so this is the basically eternal "eternal sunshine of the spotless mind" phenomena. (laughter) >> jim carrey has a problem with the girl and he goes this company and that flash it is pictures of the girl. each time they flash a picture they zap his brain and he move the memory. that's basically what these experiments do. >> rose: let me turn to aggression. how do we go from fear to aggression? >> aggression is really almost as arguably important in our society as fear is. it's responsible for war, domestic violence and genocide and we understand it much less well than we understand the neural circuitry of fear. it's highly conserved in evolution, dogs fight, cats fight and so aggression is very, very fundamental and important. we heard in a previous episode that critical experiments by olds and millner showed that if a rat stimulated a a particular center in its brain it produced a sensation of pleasure and it would do that over and over again and even before that experiments by walter hess in switzerland in the '40s showed if you stimulate a different region of the brain you can produce anger and aggression, the opposite emotion. and he showed this remarkably in cats by putting an electrode in a specific part of the brain and firing the neurons, he made this out wardly normal happy cat suddenly express rage, hiss, lay its fears back. now that's telling us about the parts of brains involved in emotion but there's a great deal of interest in the nature and nurture question. to what exstent aggression influenced by inheritance and to what extent by our environment? and we heard that insects have been good and particularly in and whether this insect dros shows aggression and it turns out that drosophila do show aggression as we can see in the movie here showing two drosophila grappling with each other over a food patch and you can see them almost like sumo wrestlers shoving against each other trying to get dominance of the food patch. why is that interesting? because drosophila breed very rapidly and are cheap to maintain. you can screen through essentially a haystack of many mutant strains of drosophila to find a need which will has a higher level of aggression than normal flies have. the next video shows an example of a genetically hyperaggressive fly strain so this is the genetic equivalent of the hess experiment where these flies have been made hyperaggressive by a manipulation of their genes and this promises into the future some insight into how genes control aggression. but i also think it's important not to assume that environment doesn't affect aggression in the this species because genes do. in fact, environment affects aggression in fruit flies almost as much as genes. so you can show if you socially isolate flies, you let one fly grow up from its pew pa in a vile and test its aggressiveness those isolated flies are more aggressive than flies housed in groups and this is true throughout the animal kingdom. >> rose: if you're isolated you're going to be more aggressive. >> you're goingtor more aggressive. >> rose: i knew that. (laughter) >> rose: >> so here's an important example of an environmental influence on aggression. a that doesn't mean that genes are not involved in this. as we heard from joe ledoux earlier, the environment can act on neurons to turn genes up or to turn genes down. in people, for example, and kerry i lewded to this earlier in his discussion, childhood trauma has an extremely important influence on how aggressive you are. there's an example of a mutation in a gene which pre-disposes people to aggression but much more so in people who have been exposed to childhood trauma so there's a clear interaction of heredity and environment. so the two go hand in hand. one shouldn't think of nature and nurture as being different things. >> i think this is a beautiful example of that interaction. if you think of this, the capability of doing harm is in all of us. it's society that guarantees which way we go. and we can be socialized to be aggressive against an alien group or we can be socialized to be respectful of foreigners and to understand how this works in a biological level is going to be extremely important. >> rose: do pro found lessons come out of this for parents? >> yes, because early experiences are so important for children. being with your child, taking care of the child, protecting them is essential. >> early trauma is not just predictive of aggression but p.t.s.d., depression, almost everything. >> many, many things. >> so we have inborn tendencies to aggressiveness like that hype thalamus and amygdala but we learn through parenting and training to keep those in check and that's due to the activity of the brain area that antonio described, the prefrontal cortex that exert this is conscious control to suppress aggressive impulse. >> before james came along there was a big philosophical school that says there's a big distinction between emotion and moral judgments. they're independent. when you make a moral judgment, emotion should not get in the way. every decision one makes is emotionally charged. >> and this decisions are influenced by social interactions. so part of what happens is i think in genocide, for example, is that it becomes socially acceptable... >> to do horrible things. >> for one group to do terrible things to another group. >> rose: but how is that... make that leap so that i understand it. >> so the interactions between groups of people socially help to take the brakes in the brain off the violent impulses and then the more people that do it the more acceptable it become, the easier it is for other people to relieve the brakes in their own brain. >> the way the nazis did it is simply to say look, the jews and gypsys are not human. they're subhuman, they're vermin. we want to cleans society. >> or the tutsis are cockroaches in rwanda. >> right. and once you dehumanize it becomes easier >> these brakes on the outside aspect of the pre-frontal cortex they don't act anymore. so you're getting these people and that's interesting. that's the really fighting ground for the cultural effect in terms of the modulation of the emotions and it can work for the good or produce horrible... >> i think one point that david made which is worthwhile is repeating and that the people think of genes as being the controllers of behavior. but genes are also the servants of the environment. their expression can be my lated but by learning by social experience. so genes are importantly influenced by environmental contingency. >> rose: with respect to aggression or anxiety but aggression are there gender differences? >> there certainly are. there's good evidence in rodents that the brains of male mice are more hard wired for aggression than the brains of females may. it's not that female mice and rats don't show aggression, they show aggression when defending their young against a threat for sure but if you look at the circuits in the brain and the cells that control aggression and certain key regions of the male brain there are actually more neurons in those regions than the corresponding regions of the female brain. there's actually a difference in the relative size of those areas and that may relate to the increase prod pencety for aggressiveness in the males of species like rats and mice. so the female drosophila will fight with each other, as will male drosophila, although a male will almost never attack a female but interestingly, when female drosophila fight they fight in a different way than males do. they show much more head-butting behavior whereas males tend to show this lunging and pouncing behavior. now, there's a master gene in drosophila that's been identified over many years by bruce baker and colleagues called fruitless and that gene controls the sexual identity of the brain. when that gene is present the brain has a male identity and if you mutate, remove that gene in a male fly its brain acquires a female identity and that can actually change the style of aggression exhibited by these two supplies against each other, that is a fly with a male body and femmize ined brain will fight with other flies like that using this female style head-butting aggression. >> rose: unbelievable. >> and if you put the female fly's brain and masculinize its brain it will fight with the lunging and pouncing brain. >> so testosterone... >> that's right, it's fascinating. >> rose: it's unbelievable. tell me the one question you most want to see answered in your field. >> we've been hearing a lot about fear, aggression, other shows we were talking about vision or movement. so we're very good in neuroscience at understanding how pieces of the brain work or little functions work. but what we don't have a s an understanding of how the brain itself work. we need a theory of the entire brain and how through that, through this operation the brain as a whole our self or personality comes out of the brain. >> i'm very interesting in understanding how we feel. there's no question we have a pretty good idea of how we molts and we have the basic idea of the circuitry circuitrys that will permit us to create this portrayal of the bod body when it is having an emotion and that's the feel. but how exactly it works we don't. and for example why is it that a feeling feels like anything? why is it that a feeling feel it is way it does? why is it that you can feel pain or you can feel pleasure. there are a number of unanswered question there is and i think like many other aspects of our minds we're going to find the answers in neuroscience. we just need to have different approaches but that's my main question right now. >> what genes mediate the risk for who develops disorders and who doesn't and then by... >> rose: what genes mediate the risk? >> for, say, post-traumatic stress disorder. is and i they's so exciting about this area, my final word would be is understanding fear disorder is far ahead of many areas of sky cy chai tri. so when we identify the genes with classic genetics we can look in the brain and it will help us understand how that part works and new therapies and ideas. >> for me it's an evolutionary question. are the genes and the brain mechanisms that control something like aggression conserved throughout ef constitution? what are the genes that pre-dispose individuals to violent acts. and importantly how can environment like social isolation act on those genetic circuits and the neural circuits as well. >> so i think that issue of conservations and the fundamental nature of aggressive and violent behavior is an extremely important one. we don't understand it yet. >> rose: where do we go next month? >> next month we'll consider depression, manic-depressive illness and schizophrenia. profound mental illnesses that have a devastating impact on people's lives but we will discuss these illnesses with people who've handled them brilliantly. >> rose: eric kandel, come back to see us next month and we'll talk about depression and schizophrenia and other things. see you then.