Also four kinds of aggression. The ma killer is the orchestrator of emotion, positive and negative. It influences the hypothalamus. The hypothalamus has many functions but we will focus on its role in aggression and sexuality. We are basically are oh scientists in my lab and we want to understand some of the most fundamental questions about aggression. How is aggression, a ehavior,onary ancient b how is that hardwired into the brain . Where is aggression in the brain . We have studied this problem in and weremice particularly interested in the relationship between the parts of the brain that control aggression and those that control mating or sexual behav ior. Mating and aggression are closely related behaviors. In nature you often find that periods of aggression are at their highest when animals are mating. These behaviors reinforce each other. At the same time, they are mutually exclusive. A male will direct mating towards a female of the species aggression towards another male. Theres a paradox. How can these behaviors be mutually exclusive but also reinforce each other in some way . We have begun by trying to pinpoint the neurons that control aggressive behavior and we have started i looking in a very evolutionarily ancient region of the brain which eric brought up call the hypothalamus. We began by trying to measure the electrical activity of cells that were active during aggression or mating, in a tiny region of the hypothalamus. We found something quite surprising. 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 was done in males, some of which were turned on when the animals were mating with a female, and some of these were active during both fighting and mating, 25 of them overlap. Was an interesting observation, a correlation, and we really wanted to understand the function of these neurons. We began by using very modern techniques now called up to genetics opto genetics to activate and inhibit these neurons. We can turn them on and turn them off with a time resolution of milliseconds. Im going to show you a video of what happens to a male mouse when you activate these aggression irans in the brain neurons in the brain. Some of the viewers might find the image a bit disturbing but what we are doing does not hurt the mouse. These are all protocols that have been approved by our institutional animal use and Care Committee and nih approved. You will see the mouse in a cage with an inanimate object. When the light comes on we are stimulating these aggression neurons in the mouse. We can actually trigger the mouse to attack a rubber glove. If there were another mouse there he would attack the other mouse as well. We wanted to ask, are these neurons necessary for normal aggression . Mice will normally fight for each other, if you introduce an insured or mouse into the cage where a male mouse lives, very shortly thereafter the resident mouse will attack the intruder. We ask if we shut these neurons off, can we stop a fight dead in its tracks . Will show you,eo its possible to do that. These mice are fighting naturally. When the light comes on we inhibit these neurons and the fight stops. We will show you that again in slow motion. The mice are fighting and suddenly the light comes on, we stopped the attack dead in its tracks. Charlie how did the near on snow to respond neurons know to respond to light . Genetically implant in these neurons deep in the brain a protein that comes from a light sensitive algae. That protein makes an ion channel through the membrane of the near on that turns the near on of the neuron that turns the neuron on only when light activates this channel. That shows us that these neurons are necessary and sufficient for aggression. We discovered as we were manipulating the conditions for turning these neurons on very surprising. You needed high intensity stimulation to activate aggression but low intensity stimulation would promote mounting behavior. The mouse which i to mate with whatever other mouse was in the cage would try to mate with whatever other mouse was in the cage. We could switch the behavior of the same animal from attempt of mounting to a mixture of mounting and attack just by increasing the intensity of light. That tells us that in this tiny region of the brain there is a mixture of neurons controlling both the mating instinct and the fighting instinct, and perhaps that will account or may account for the tension between the sex drive and the aggressive drive. Charlie its extraordinary. It explains why aggression ression. To sexual aggerssio a lot of people think aggression is more prevalent in people with mental illness. Mental illness on its own does not increase the rate of aggression. It is more likely to occur in individuals with issues of Substance Use dependence, especially prior history of aggression. Everyone gets very concerned when Mass Shootings happen. This person must be mentally unfit. Studies, itoss doesnt pan out. There are multiple forms of aggression. There is socially sanctioned aggression, such as fighting in war, medically induced aggerss ression. The two big ones will be impulsive aggression and premeditated aggression. Impulsive aggression is not exactly spontaneous. People perceive a threat or frustration and their threshold to blowup is very low. They blow up an experience or display a temper touch or more physical aggression. Premeditated aggression, which can happen in anybody, is taught through thought through. The people most likely to do that is psychopaths, maybe 1 of the population. Some people have a disorder of impulsive aggression, 3 or 5 to 6 . Those important distinctions to put forth, because we have an impulsivew to treat aggression. We are not sure how to treat premeditated aggression. Charlie what did we see at the nero biological level . People with aggression is similar to what were hearing at this table. The doctor talked about 4 of boys being chronically aggressive. We also see the same sort of thing biologically pretty see problems with serotonin function, where serotonin function is diminished. We see evidence of heightened other neurotransmitters that will facilitate aggression. We see problems in the frontal area of the brain. We present to these individuals, pictures of individuals who are angry or threatening, the amygdala will overact to that stimulus compared to healthy volunteers. That correlates with how aggressive these people have been over the course of their lives. Thing going along with this is serotonin and the amygdala really have to do with the tendency to be aggressive. What makes you aggressive in the here and now has to do with how you interpret social signals. People that are aggressive it may very well be because they had been aggressive as a child 10 to have problems of social internation processing. They dont take in enough information about whats going on and they make a hostile inference as to what the other people is doing. You can have a situation where the threshold may be high or low and when you are coming into the to is that you are prime think somebody brushing up against you are looking at you funny is threatening or frustrating to you. You have a serotonin system in the frontal lobe that is not working so well. You have a high accelerator, breaks are bad, you will have a crash. One of the key things that emerged is the treatment of depression often is designed to increase the level of serotonin. Is there a increased incidence of this kind of aggression and people who are depressed and have low levels of serotonin . Not necessarily. The early studies i did were interesting in that. We saw this problem in individuals who did not have a primary mood disorder. Their brain systems involved in activation are not working well. When they aredism severely depressed. Charlie we talked about certain individuals who cannot control their impulses. M. L. Has been talking about people in a hospital context. We work with people at the street level were violent psychopaths, even killers. Charlie what the psychopath mean . An individual who lacks conscience, remorse, guilt. Because of that lack of feelings, they do outrageous things. There stimulation seekers, their impulsive. There is the cold, calculating, callused type. Then you have the antisocial lifestyle, doing horrible things to other people. We have been studying their brains using brain imaging to look to see what part of the brain may not be working right, what part may be physically different. What we find in normal people is that their prefrontal cortex is working well, as you see there, in the green. This is where we brain scanned murderers. What we see our murderers who are impulsive, they do not plan there murderers, they are hotblooded in terms of their homicide. What we see on the left is poorer functioning in that frontal region of the brain. Why is it that that part of the brain can predispose to aggression . It is a part of the brain involved in checking on impulsive behavior. We all get angry at times. What stops us lashing out . We have a good frontal cortex that is working well to regulate and control our aggressive behavior. Those are hotblooded murderers, but what about the coldblooded murderers . When we brain scan them, they had pretty good frontal functioning, which makes sense because these are killers who premeditate their homicide. They had the wherewithal to do that. The interesting question becomes, what is it then that is producing them to be violent in a predatory fashion . Lets turn to the next slide. We will look at another brain region. This is the m mikula on the left. Dala on the left. Coldblooded psychopaths, they have a physical shrinkage in the amygdala. It is reduced in size by 18 . On the right you can see the areas within the amygdala colored in blue that are physically deformed. Dala is important in generating emotions. If there is a shrinkage, that will reduce fear. What stops a lot of us breaking the law of the lands, we are frightened about the punishments we would get if we were caught. Youif you lack that fear, are more likely to commit offenses in a coldblooded fashion. Theres more to it than that. On the left you can see where it is located in the brain. Can seeight, you theres greater activity in psychopaths when they are anticipating rewards. We have the idea that psychopaths are reward driven. They want the goods, just like an addiction. The idea is anticipation reward is part of the brain, firing up a lot more. Maybe that is why psychopaths are more likely to pursue rewards and gains that they want. They have the drive to do that. And they dont have the emotional amygdala to hold them back in a way to give them anticipatory fear. This is a spectacular series of findings. When i was a medical student, none of these imaging techniques were available. You had very little insight of what was going on and the living brain of people. We now have insight into the biological substratum of different kinds of aggressive syndromes. Just the beginning, how much we have learned, different categories, impulsive versus premeditated, different categories. Charlie even affecting the size of the amygdala. The question is, because of your reference to imaging, can you look at imaging and decide it is most likely to be aggressively violent . Its a great question. We are beginning to get clues about who may be more likely to be violent in the future. Myself and colleagues brain scanned males in the community. Those individuals with a smaller volume to the amygdala were more coldblooded. They were four times more likely to commit a violent act in the next three years. That is prediction over and above right history of violence, prior history of psychopathy. Get valueinning to used by imaging to try to understand who are at risk for becoming the next generation of future offenders. Kindie are we seeing this of research used in trials, in criminal trials . The key question here is if a psychopath is what is causing that amygdala sure gige shrin kage . It could be genetic. We also know that trauma reduces the size of the amygdala in children. Neglect reduces the size of the amygdala. I dont think psychopaths ask to threen with an amygdala sizes too small. If that brain empowerment predisposes them, alters them, doing the terrible things they do, the fascinating question as to what extent do we hold them fully responsible for their actions . Evidence. Not dna probabilistic statement, and that is imperfect in front of the law. As techniques get better and we see not only the amygdala the amygdala is associated with isormality, danger associated with another abnormality, we will be in a better position. This behavior is essential for the Proper Development of parenting is one of the strongest and most enduring social bonds in human societies are at parental behavior is widely concerned in the animal kingdom. In mammals, females lactate and they take riemer responsibility of the parental care. Female see this temperance is watching over the first chimpanzee is watching over her child. What about fathers . The contribution of males in parenting is very variable. , for example in the silverback monkey and gorilla playing with his infants, in some species males are paternal, they nurture their young. In some other species, males attack the children and sometimes kill them. Biologist in my group used a Laboratory Mouse to try to understand basic biology of parenting behavior. We would like to identify the brain areas that are involved in driving parental behavior and we would like to understand how these brain areas are regulated, in order to have animals that are parenting and some animals that are neglecting their infants. Mothers as well as nonmothers are spontaneously maternal. Which means that when they are put in presence with cubs, they will spontaneously build a nest, they will groom them, and huddle with them for long periods. In contrast, males are infanticidile. However, males that have access to the females become paternal three weeks after meeting with a female, which corresponds exactly to the gestation time in mice. Males who become fathers also become paternal. Ook advantage of these extremely interesting paradigm and differences in behavior between males and females and maless and infanticidile to try to understand what are the brain role. What are the neurons that drive parental behavior . In the first set of experiment we identified a specific set of cells in the hypothalamus activated during parental behavior. Neurons,sk all these required for the parental drive. In a subsequent experiences experiments, we ablated these neurons in parental males and females. Surprisingly and remarkably, now these animals neglect their infants or attack them. These experiments suggest these near runs are required for parental behavior. Experiments, we ask whether the activity of these new runs was sufficient to create parental behavior. We took aggressive males and we artificially stimulated these nurturing neurons. Amazingly, these aggressive males stopped attacking the cubs and they groomed their infants. What this experiment says is the activity of these near ons is sufficient to drive parental care. Experiment we identify a set of cells in a different area of the hypothalamus that is activated when aggressive males attack their infants. We call these the parental neglect neurons. In another experiment, we activate these neurons in ,emales and found these females instead of caring for their infants, now neglect or attack them. Overall, these experiments suggest the brain set of components, a cells in the hypothalamus that drive parental behavior and a net of set of another set of cells that drive parental neglect. Opens new opportunity to understand the control of parental behavior and why some animals are parental and some animals are neglecting or attacking these infants. Parental behavior is widely conserved among animals. These also raise the possibility that the function and regulation of the cells is widely conserved across the animal kingdom. Charlie how do you stimulate the neurons to make the aggressive males more nurturing . Modern methodsse in nero science neuroscience that enable to shine light on neurons that have been genetically modified and have an ion channel that is light activated. The activity of genetically defined population of neurons. There is been fascinating work done by teams understanding the evolution of parenting of bonding between males and females. There is a very nice system where some species are monogamous and some are polygamists. Males and females form these long time pair bonds and both are nurturing towards their young. What has been found in this system is that not only are the high levels are there higher levels of oxytocin, but in the males there is a similar hormone produced by the hypothalamus which seems to be important in determining both paternal behavior and pair bonding behavior. In the monogamous species there are more receptors and higher levels of [indiscernible] we have oxytocin in females which seems to be important in driving pair bonds and maternal behavior. [indiscernible] did a fascinating series of experiments determining how oxytocin impact some female maternal behavior and for males, pair bonding and parental paternal behavior. It monogamy that produces the higher levels of oxytocin or is it higher levels of oxytocin that produce monogamy . Susanne oxytocin is primarily involved with maternal behavior. Teams whoe same worked on how vasopressin relates to pair bonding and maternal behavior in both has shown that you can take both that are not monogamous and at best the present and make and add vasopressin and that changes their behavior. What is it about human biology that is both similar and different to other primates is what drives our research. Humans have a large brain and exceptionally long juvenile and infancy periods. Because we are born so helpless and so unable to take care of ourselves, parenting becomes exceptionally important. Human babies are totally defenseless and even throughout their juvenile period they need much more investment by their than similar species that are closely related to us. That tells us that in humans particularly, understanding the role of parenting behavior and the biology of behavior is very important. Charlie what is the effect on children who are deprived of nurturing . Aree know that children exposed to a continuum of care. This infant and mother are having a wonderful conversation. This is what we want to see in all infants and mothers are at mothers. Under profound deprivation, all of that is missing. Inhave a pair of twins directing. Sittingmber of babies in institutions, the lack of caregivers. There is one you can see in the back. Theres a very low investment in these children, unlike the videos we saw in the beginning. Interaction,social we think, plays a fundamental role in building the brain. What we started to observe was in the study, what happens to the developing brain and kids growing up in institutional care. We formed a manipulation in which we saw a large number of children abandon the institutions abandoned in institutions and romania. Some were placed in high quality foster care and some remained in the institution. I want to show you a video of what a child at the age of two looks like. This is on an outing with a bunch of kids from an institution or you notice the shes 22ing over, months of age, shes been in the institution close to