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Columbus Circle, Manhattan campus ​Translator: Queenie Lee Reviewer: Peter van de Ven What would art be like without emotions? It would be empty. What would our lives be like without emotions? They would be empty of values. So a famous classical poet said, "We hate and we love; can one tell me why?" – Catullus. Science does not answer why questions; science answers how questions. But the why question would be answered as follows. We have feelings because they tell us what supports our survival and what detracts from our survival. And I've been in this field now for half a century, and it's been a fairly lonely field because when I was a student in electrical engineering, I started getting bored, and I worked in the back ward of a psychiatric hospital and saw human tragedies, their emotional tragedies. No one knew what emotions were, how we get these feelings, so I decided to shift to neuroscience – first clinical psychology, then neuroscience, that is the only path to understanding how we feel. This seems to be an impenetrable mystery, but it is potentially penetrable with neuroscience, especially if we take the emotions of animals seriously. And a friend sent me these pictures. A little fawn was injured, and the dog took a special interest in the fawn. Now is the dog thinking - (Laughter) [You smell good?] Or interesting? We cannot penetrate the cognitive mind of animals even though they are very skilled in living as we saw earlier this morning. So second picture. Is the dog saying, "I like you"? [I want to eat you?] (Laughter) or even "I love you"? We cannot penetrate those kinds of thoughts, but we can penetrate feelings scientifically, but only with neuroscience. And if we understand the emotions of other animals, I think we will begin to understand our own emotions. An artist drew this for me about a year ago, and even chickens have emotions, so we mapped out sadness systems in chickens, and they turn out to be the same as in guinea pigs, and it looks like they're very similar to those in human brains - that's quite a shocker. Now the animal mind is of great interest to us right now, and I suspect that if we really focus on their feelings, we will finally begin to understand our own. So our approach has required neuroscience, and we can actually turn on emotions by stimulating specific areas of the brain. We've known this for quite a while, but I was among the first to ask: when we turn on emotion, does the animal feel good or bad? The animal can give us that answer because it can turn on this stimulation if given the chance, or you can turn it off, and that is our measure of feelings. So we're very similar at the bottom of our minds, and we're very very different at the top of our minds. We are the cognitive creatures, they are the emotional creatures, but they, obviously, must have thoughts about their lives and the world. So this is a powerful emotion, we get angry and we get scared because of very similar systems in our brain. And it turns out that wherever you produce this anger response in animals, they turned it off; they don't like that feeling. So there is something like anger in the animal brain, and if we understand those circuits, we might have new treatments for irritability disorder, someone who is continually getting angry, and you say, "Take a pill," well, we have no pill. But we do have knowledge about seven basic emotional systems. We call them Primary Emotions, we capitalize them because this requires a specialized terminology for science; otherwise, we have confusing conversations because of so many words. So what feeling does the SEEKING system, others still call it the reward system, the feeling is not pleasure, the feeling is enthusiasm, this is diminished in depression. And I'll show you one clinical trial we're running where we're facilitating enthusiasm directly through deep brain stimulation. That's the feeling (Laughter) in the vernacular, I'm using everyday terms here, of course. There are many sources of anxiety in the world, but we only have one powerful fear system. And what shall we call the feeling of LUST? Well - (Laughter) I thought of "passion," but that is too broad a term. Now CARE is tender and loving, it's hard to describe these pre-verbal powers of the mind. The PANIC system generates loneliness and sadness, and like I've told you, in chickens we measure separation calls. So PLAY brings you great joy. If you have too much psychological pain, namely the PANIC system, can cause panic attacks also. This is the gateway to depression: too much psychological pain. If it's way beyond bounds, people begin to think about killing themselves. So we have developed one antidepressant by focusing on the molecular biology of happiness and joy, and it is currently in human testing. Yes, that is the way tender, loving feelings feel in the mind, it has a certain dynamic. It comes across in the body the way the mother caresses a child, and a child that doesn't have that will have psychological problems for the rest of his or her life. So if we understand these emotional systems, some of them will be rewarding, some are punishing, but they're never neutral, and that is the evidence that they have emotional feelings. And we can predict that if we stimulate the RAGE system in humans, they will be very angry, and it has been shown, just accidentally during surgical procedures. So let's focus on this PANIC system that we started to study 45 years ago. When you separate a young one from the mother, they begin to cry because the


mother is the absolute source of security, and we started measuring this crying and trying to figure out a neuro anatomy of it and the neurochemistries, and that has led to new treatments for depression as well as for suicide. If you take a little bird, and they're born and they're walking around and they're crying, crying, crying looking for their mother, as soon as they find the mother's wings, they settle down and they're comfortable, and we can simulate this by simply holding the little ones in our hands, they immediately quiet down, they feel comfortable, their beak goes down, and they fall asleep. This is because we're activating chemicals that counteract psychological pain, and the most powerful chemistry for this turns out to be brain opioids - that's a shocker. It turns out that our love and our attachment are partially addictive phenomena; they ride upon our internal opioids. They provide us with a sense of security that everything is right in the world. So there we are, that is the reason we become addicted to these molecules, and it's a tragedy of our country that we put people in jail as opposed to putting them in treatment facilities to explain what's happening in their brains. I think it would be wonderful if our government had an open conversation about the sources of addiction in our brain. Opioids mediate motherly love, the attachment bond between mother and child, the attachment bond between loving adults. And then we found that the molecule that releases milk from the breast also is very powerful in the brain in reducing the panic response, the separation distress response, and lo and behold, the molecule that manufactured milk in the breast is equally effective in reducing separation distress. So the physiology of motherhood is the physiology of love, and we mapped this system with deep brain stimulation in guinea pigs first and then chickens, and the anatomy was the same, the neurochemistries were the same. And you see that in the guinea pig picture, a deep sub cortical system where you can activate the separation cries, and even if you take an adult guinea pig that no longer cries, if you put an electrode in there, they will cry like a little baby as long as you provide the stimulation. So where does it go? It kind of develops inhibition from higher brain areas. Testosterone is something that counteracts crying, that's why there's a large difference in male and female emotions. Antonio Damasio imaged emotional feelings for the first time and found a very similar trajectory, and then Jon Kar Zubieta, the University of Michigan in Ann Arbor, found that human depression and sadness were low opioids in these same brain areas - remarkable! We are brothers and sisters under the skin with all the other animals, which provides us with a special responsibility for how we treat them in this world of ours, the wonderful pictures we saw art share with you. So we have generated three new concepts. The first one is to use safe opioids, not only to treat depression, and buprenorphine is a safe opioid because you can't kill yourself with it. Respiratory depression does not get so extreme because it begins to block its own action at higher doses, and this could be used for depression for the last 30 years, but we don't have a culture that permits this. And we're testing this as an anti-suicide agent in Israel, so we're using the Beck suicide inventory in people that are thinking about taking their lives. During the first week in these four individuals, all four showed benefits from both placebo and buprenorphine. Now placebos release opioids in the brain, but by the second week the placebo was no longer effective but buprenorphine still was. This led us to test 60 people, double-blind, placebo-controlled, and that trial will be finished by Christmas. And it will work, I am confident. The second concept has been to use deep brain stimulation to restore enthusiasm for life, and this cannot be easily done in America. I did convince colleagues in Europe who are doing deep brain stimulation for Parkinson's disease to move their electrode slightly into the SEEKING system, because we know from animal work, if you over-stimulate the separation PANIC system, it decreases the enthusiasm for life as this attempts to summarize. And if you could elevate the seeking mood directly, the enthusiasm mood, it should have antidepressant effects, and lo and behold, they published this paper about the middle of July: six of seven depressed people that had not gotten any benefits from anything, including electroconvulsive shock, showed dramatic elevations in the desire to live and enthusiasm to do things in the world, they were basically normalized by facilitating the SEEKING system. And finally, we have been using PLAY as a model for identifying new molecules for antidepressants. What would be better than some molecular pathway to facilitate social joy? The only thing better is to live in the human family, happily, with art, culture, music, all of the fine things in life. Of course, human relationships are the best antidepressants, but we have joy systems in the brain, and we can figure out the molecules, and we have done that with my Northwestern colleagues, and we have developed a new antidepressant that came from the analysis of cortical changes in gene expression patterns and checking out the candidates as possible antidepressants. And the first couple were antidepressants, but they also had medical dangers, but we found one that didn't have any of these problems. By analyzing rats playing, purely positively, I've gotten a famous name of the rat tickler - (Laughter) (Video) Jaak Panksepp: We have listened to animals playing - this is from 1998 - what appeared to be the sounds of laughter, and we studied these for a couple of years without quite understanding that this might be laughter. And then one day we decided to tickle some animals, and we realized that we had to look at the sounds at a very different register than we can hear, so we obtained these transducers that are called bat detectors, that can bring very high frequencies down to our auditory range, and when we did this and


we listened in, we could tickle animals and generate a lot of vocal activity that appeared to be laughter. These animals would begin to enjoy our company, and they would start to play with our hands, and wherever we will put our hands they would follow it. And when we tested these animals to ask whether they were enjoying this kind of activity, the unambiguous answer was yes. (Laughter) (Applause) (On stage) JP: I might share that the day before that was filmed by the BBC, our first publication in that area, they told me I had no more than a year to live, no matter what. So, glad to be here with you. (Cheers) (Applause) If we finally take the emotions of the other animals seriously, we will finally understand how we have these feelings of joy and sorrow, anger and sadness. Essentially, this molecule is called GLYX-13, it's a very long story that I don't have time to share with you here, but it is already in phase two FDA approved human testing. Single injection produced antidepressant effects immediately, and those effects from the one treatment lasted a week. No psychiatric medicine has yet been developed by human knowledge; so far everything has been discovered by serendipity and chance. Science has only refined the molecules. This may be the first psychiatric medicine to come from human knowledge by taking animal feeling seriously, and this has no poisonous properties as far as we can tell; it's also not addictive. So finally, this is the conclusion of a 50-year-old journey. I do hope that people take a very different attitude to animals than has been common, in research and a variety of other human activities. We are brothers and sisters under the skin, and we better recognize that. And once we understand them, we will finally understand ourselves. Thank you. (Applause) Bard Graduate Center.

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