Rose funding for charlie rose has been provided by american express. Rose additional funding provided by and by bloomberg, a provider of multimedia news and Information Services worldwide. Captioning sponsored by Rose Communications from our studios in new york city, this is charlie rose. Now, in all these discussions, were going to come back and forth to certain brain regions and four regions are particularly important. The prefrontal cortex, the migd leand a hypothalamus. The prefrontal cortex is in executive function and character information. And defects in the prefrontal cortex often can lead to aggression. The ventral strightum is involved in certain kinds of aggression. The amygdala is the org administrator of emotion both positive and negative and influences several brain systems particularly the hypothalamus. The hypothalamus has many functions. Well focus in particular its role in aggression and sexuality. So, charlie, were basic neuroscientists in my lab and we want to understand the most fundamental questions about aggression. How is aggression which is an evolutionary ancient behavior, you see it throughout the animal kingdom, how is that hard wired into the brain . Where is aggression in the brain . And weve studied this problem in flies and mice and were particularly interested in the relationship of the parts of the brain which control aggression and mating because theyre closely related behaviors and, in nature, you often find periods of aggression are at their highest when animals are mating and these behaviors reinforce each other, but, at the same time, theyre mutually exclusive. So a male will direct mating towards a female of species, aggression towards another male. So there is a paradox, how can these behaviors be mutually exclusive but also reinforce each other in some way . So weve begun by trying to pinpoint the neurons that control aggressive behavior and weve started by looking in a very evolutionary ancient region of the brain which eric brought up called the hypothalamus. So we begin by trying to measure the electrical activity of cells that were active during aggression or mating in a tiny region of the hypothalamus and we found something quite surprising and that is, within this very small region of the brain, we found a mixture of neurons, some of which were active, turned on when the animals were fighting, this is done in males, some of which were turned on when the animals were mating with a female and, interestingly, some of these neurons were active during both fighting and mating, about 25 of them overlap. So that was a very interesting observation. It was a correlation and we really wanted to understand the function of these neurons. So we began by using very modern techniques, now, called optogenetics to activate and inhibit these neurons and we can pinpoint this activation with a high level of accuracy directly to specific cells in the brain that are active during aggression and turn them on and turn them off with a time resolution of milliseconds. So im going to show you a video of what happens to a male mouse when you activate these aggression neurons in the brain. I should say before we show the video some of your viewers might find the image a bit disturbing but what were doing doesnt hurt the mouse and these are all protocols approved by the institutional animal use and Care Committee and are n. I. H. Approved. So you will see the mouse in the cage with an inanimate object. When the light comes on were stimulating the aggression neurons in the mouse. So we can actually trigger the mouse to attack a rubber glove. Of course, if there were another mouse there, he would attack the other mouse as well. So we wanted to ask are these neurons actually necessary for normal aggression . So mice will normally fight with each other, for example, if you introduce an intruder mouse into a cage where a male mouse lives. Very shortly thereafter the resident mouse will attack the intruder, he doesnt like somebody impinging on his territory. So we ask if we shut the neurons off can we stop a fight dead in its tracks . The next video will show you its possible to do that. The mice are fighting naturally. When the light comes on, we inhibit the neurons and suddenly the fight stops. Well show you in slow motion. You can see the mice are fighting. Sund through light comes on. Boom, we stopped the attack dead in its tracks. Rose i dont understand thousand neurons know to respond to light. The way that we do this is we genetically implant in these neurons deep in the brain a protein that comes from a lightsensitive algae, and that protein makes an ion channel through the membrane of the neuron that turns the neuron on only when light activates that channel. So we can convert these are neurons into light sensitive neurons. So that shows us that these neurons are necessary and sufficient for aggression. Different kinds, those that activate the neurons and those that shut it off, and he can do either. So we discovered as we were manipulating the conditions for turning these neurons on something very surprising, and that is that you needed tensity stimulation wouldowto promote mating whaifer. So the mouse would try to mate with low intensity stimulation, whether male or female mouse. And we could switch the behavior of the same animal from attempted mounting to a mixture of mounting and attack just by increasing the intensity of light. So that tells us that, in this tiny region of the brain, this is a mixture of neurons that are controlling both the mating instijt and the fighting instinct and perhaps that will or may account for the tension between the sex drive and the aggressive drive. Rose extraordinary. Iits extraordinary. It also explains why aggression can lead to sexual aggression. Is it an amazing set of findings. A lot of people think aggression is important in people with Mental Illness. The fact is Mental Illness on its own does not increase the aggression. It may depend on other factors like Substance Abuse and prior aggression. Everyone gets concerned when Mass Shootings happen this, person must be psychotic, mentally unfit, and those are very individual situations. When you look across large epidemiological studies, it just doesnt pan out. There is multiple forms of aggression. Socially sanctioned aggression such as fighting in war. Metal aggression. But the two big ones are impulse aggression and premeditated aggression. And impulse aggression is not exactly spontaneous. People perceive a threat or a frustration and their threshold to blow up is just very low. So they just blow up and experience or display a temper tantrum or physical aggression. Primitive aggression which can happen in anybody is premeditated aggression is thought out. The people who do that are more likely to be psychopaths. And the number of psychopaths are maybe 1 of the population. But people have intermittent explosive disorder, more like 3 to 6 , so thats much more the case as far as thats concerned. And those important distinctions to put forth because we have an idea how to treat impulsive aggression. Were not quite sure how to treat premeditated aggression. Well say more about that. Rose what do we see at the neurobiological level . What we see in people with aggression is very similar to what were hearing at this table. Dr. Tremblay talked about 4 of boys being aggressive. We see the same things biologically, problems with serotonin function, where usually serotonin function is diminished. We see evidence of highent other nerve transmitters to facilitate aggression. In terms of systems, we see problems in the frontal area, the amygdala and other aspects of that. When we present these kids who are angry or threatening, the amygdala will overreact to that stimulus compared to Healthy Volunteers and that correlates with how aggressive these people have been over the course of their lives. Now, an important thing going along with this is se serotoninn the amygdala has to do with the tendency to be aggressive, but what makes you aggressive in the here and now has to do with how you interpret social signals. So people who are aggressive and it may well be because they had aggression as a child tend to have social information processing. So they dont take in enough information about whats going on and make a hostile inference as to what the other person is doing. So you can have a situation where your threshold may be high or low and where youre coming into the day is that youre primed to think that somebody brushing up against you or looking at you funny is threatening to you or frustrating to you. You have an overactive amygdala, a serotonin system and the frontal lobe is not working well, the brakes are bad, high accelerator and the brakes are bad, youre going to have a crash. Its interesting when charlie and i did a study on depression, depression is often designed type crease serotonin. Is there increased in aggression and people with low levels of serotonin. Interestingly, not necessarily. The early studies i did were interesting in that we saw this problem in individuals who didnt have a primary Mood Disorder and what we think is going on is that ther their bran systems involved in activation are not working well and will make a Suicide Attempt because thats going on. Low serotonin is bad brakes. Rose adrian, let me talk to you about certain individuals who can not control their impulses. Yes, emil has been talking about people in a hospital context. What we do is work with people likely at the straight level, people who are violent psychopaths, even killers. Rose what does psychopath mean . Its an individual who lacks conscience, lacks remorse, lacks guilt and because of that lack of normal emotional feelings, they do outrains things and theyre stimulation seekers, impulsive. There is the cold, calculating callous type and have many of the and thety social lifestyles, doing horrible things to other people. They have been studying brain imaging to look to see what part of the brain might not be working right, what part of the brain might be physically different. What we find in normal people, of course, is their prefrontal corps text is working well as you see there in the green. If we can have the next slide, this is where we see murderers. The murderers are impulsive, very hot blooded in terms of their homicide, and what we see there on the left is poorer functioning in that very frontal region of the brain. So why is it that that part of the brain can predispose to aggression . Its the part of the brain thats involved in checking on impulsive behavior. We all get angry at times, dont we . What stops us . We have a good frontal corps text working well to regulate and control our aggressive behavior. So those are hotblooded murderers, but what about the coldblooded murderers . When we study them, they have pretty good frontal functioning which makes sense because these are the killers who premeditate their homicide and plan ahead and they have the wherewithal to do that. The interesting question is what is it thats producing them to be violent in a predatory fashion . So lets turn to the next slide where well look at another brain region and this is the amygdala. On the left you can see where its located in the brain. What we find when we study coldblooded offenders, psychopaths, they have a shrinkage, a physical shrinkage in the amygdala, reduced in size by 18 , and on the right you can see the areas within the amygdala covered in blue that are physically deformed. The the amygdala is very important in generating emotions, as eric said to begin with. If there is a shrinkage in the amigd larks that will reduce fear. What stops a lot of us breaking if law of the land . Were frightened about the punishment we would get if we were caught. But if you lack the fear and have the impairment to the amygdala that normally produces this anticipated fear that stops us from committing crime, well, youre more likely to commit offenses in a coldblooded fashion. There is more to it than that, however. There is yet another brain region called the ventral striatum. On the left you can see where its located in the brain. On the right you can see there is greater activity in psychopaths when they are anticipating rewards. So we have the idea that psychopaths are reward driven. They want the good. Exactly just like an addiction. Rose so thats a stimulation to the brain . The idea is an ant pays rewards that part of the brain that gets hooked on reward is firing up a lot more. Maybe thats why psychopaths are more likely to pursue rewards and gains that they want. Theyve got the drive to do that and they dont have the emotional amygdala to hold them back in a way to give them that anticipatory fear that would normally result. This is a spectacular series of findings were discussing here, charlie, because when i was a medical student, none of these imaging techniques were available and you had very little insight of what was going on in the living brain of people. We now have insights into the biological substratum of different kinds ofsi of ofsin dropples thats remarkable. We can see how much weve learned, different categories even affecting the size of the amygdala. Rose the question is because of your reference to imaging, can you look at imaging and decide who is most likely to be aggressively violent . Thats a great question and we are beginning to get some clues about who may be more likely to be violent in the future. For example, myself and colleagues brain scanned just males in the community. Those individuals with a smaller volume to the amygdala were more coldblooded, so to speak. They were four times more likely to commit a violent act in the next three years and thats prediction over and above prior history of violence, prior history of psychopathy. So its not perfect prediction by any manner of means but we are beginning to get added value by imaging to try towns who are at risk of becoming the next generation of offender. Rose are we seeing this kind of research used in criminal trials . The key question here is if a psychopath is i mean, first of all, whats causing the amygdala shrinkage . It could be genetic or how the brain diverged, but we also know trauma reduces the size of the amygdala in children. Neglect reduces the size of the amygdala. For whatever reason, i dont think psychopaths have to be born with an amygdala thats three sizes too small. If that brain impairment predisposes them, raises the odds of them doing the terrible things they do, the fascinating question is to what extent do we hold them fully responsible for that action . This is not dna evidence. This is not like saying im responsible, david is not, definitively. This is a problemistic statement and that is imperfect in front of the law. So it needs to get bert. When the amygdala is associated with this abnormality, that means danger, and when associated with another abnormality its unrelated, then well be in a better position. Human parents naturally die young and these behaviors are essential for the Proper Development of the child. In addition, parenting is one of the strongest and most enduring social bonds in human societies. Remarkably, parental behavior is widely conserved in the animal kingdom. In animals, females lactate and, therefore, take primary responsibility of the parenting care, as can be seen in these very nice slide, these female chimpanzee is watching over the first step of her child. So females are very maternal and not only in mammals but some species of birds, frogs, reptiles, insects. What about fathers . Well, the contribution of the males in parenting is very vairable. In some species, for example in this silverback gorilla playing with the infants, in some speeshts male are paternal and nurture their i dont think and in other species sometimes attack the children and kill them. Im a neurobiologist and my group used the Laboratory Mice to try to understand the basic biology of parenting behavior. We would like to identify the brain areas involved in driving parental behavior and would like to understand how the brain areas are regulated. In order to have animals that are parenting and some animals that are neglecting their infants. Now, in females, mothers as well as nonmothers are spontaneously maternal, which means that when they are put in the presence of pup, they will make a nest, groom them and cuddle with them for long periods. In contrast, males will readily attack the pups and kill them. However, males that have access to the females become paternal three weeks after mating with the female which correspond exactly to the gestation time in nice. In other words, men who become fathers also become paternal. So we took advantage of this extremely interest paradigm and differences in behavior between males and females and fathers and infanticide males to try towns what are the brain areas involved in those behaviors. The first question we ask are what are the neurons that drive parental behavior . And in the first set of experiments we identify a specific set of cells in the hypothalamus that are activated during parental behavior. We then ask are the neurons required for the parental drive . In the subsequent experiment we obliterated these neurons in parental males and females. Remarkably, none of the animals negligent or attack the infants. So this experiment suggestion that the neurons are required for parental behavior. In the next experiment, we ask whether the activity of these neurons was sufficient to drive parental behavior. This time we artificially stimulated these nurturing neurons. Amazingly, these aggressive males stopped attacking the pups and instead groomed their infants. What the experiment says is the activity of the neuron is sufficient to drive parental care. In another experiment, we identify a set of cells in the different area of the hypothalamus that is activated when aggressive males attack their infants, so we call these the parental neglect neurons. In another experiment, we activate these neurons in females and found these neurons now, these females, instead of caring of their infants, now neglect or attack them. So overall, what these experiments suggest is that brain has two components, a set of cells in the hypothalamus that drives parental behavior and another set of cells that drive parental neglect. We are very excited by these results because it opens new opportunity to understand the control of parental behavior and possibly why some animals are parental and some animals are neglecting or attacking these infants. Now, parental behavior is widely observed among animals and these raise the possibility that the function and the regulation of these cells is widely conserved across the animal kingdom. Rose how do you stimulate the neurons to make the aggressive males more nurturing . We use modern methods in neuroscience called optogenetics that enable to shine light on neurons that have been genetically modified and have an ion channel that is light activated. So, in other words, we drive the activity of genetically defined population of neurons. Rose fascinating. Sususanne, talk about how i