01. An Eraser in My Brain, Part 1

Part 1

Pulitzer prize-winning New York Times journalist Alissa Rubin talks with Dr. Stieg about the helicopter crash that seriously injured her, and the long road to healing her body and her brain.

Dr. Stieg: I'm happy to have my patient, the New York Times Baghdad Bureau Chief and Pulitzer Prize winning journalist Alissa Rubin. As our special guest in 2014 Alyssa was seriously injured and nearly killed in a helicopter crash in the Middle East. Her skull was fractured in addition to many serious injuries so often with traumatic brain injury, we hear about the events, but have no idea about what the patient goes through. Today, Alyssa will share her story — a long and miraculous recovery. Welcome Alyssa. So just to set the pace and tone, can you go back to that time in 2014 and tell us why you were boarding this helicopter in Kurdistan and then what happened?

Alissa Rubin: I was going on the helicopter because as you may remember, there were between 20,000 and 50,000 Yazidis who had fled from an area that the Islamic State had invaded in Northern Iraq. They had gone first to Mosul, which is the place everyone's heard of. And then they branched out into other areas. We knew that the Kurdistan and Iraqi, sort of, military were taking with them food, water, sort of very, very basic supplies to leave for the refugees who were running out of water. It was—

Dr. Stieg: So these people were living there to escape from— they weren't living there by choice?

Alissa Rubin: Well, Oh no, they were certainly not living there by just, they had fled there and they had fled with really nothing, pretty much. Some of them were barefoot. It was an extraordinarily harsh environment and particularly in summer in Iraq is scorching really hot. It's dry. It's a lethal environment, particularly for vulnerable people.

Dr. Stieg: So you were going there then to just see—

Alissa Rubin: To see what it was so that we could tell people, as a journalist, you want to see it yourself. And so I was very excited and fought very hard to get a place on the helicopter going up and really very unworried. I've been on a lot of helicopters and mostly US military, but others as well. I don't ever worry about it.

Dr. Stieg: Looking back now, having read what you described, is that a helicopter you'd actually want to get on? It sounded to me like it was overloaded, overtaxed...

Alissa Rubin: Well it wasn't overloaded going up. And after all, that was where you made the decision was based on, you know, what was the number of people on it and what was in it and what was in it was, you know, lots and lots of water, bananas, bread. I remember very clearly worrying that I was crushing the bread and then the bread wouldn't be very good to eat because there were no seats on this helicopter. This is a metal tube in the sky held up by a propeller. I had talked to the helicopter pilot before I got on and I knew he was a very experienced person. So that gave me quite a bit of confidence. And there was a member of the Iraqi Parliament coming up. The only Yazidi member. And I thought, well, if they're going to put a member of Parliament on it, you know, what's there to worry about. And so we got up there, and there were very, very ill people, elderly children, people could barely walk. And the pilot I think really had a heart of gold, and he wanted to help as many as possible. And the people just rushed onto it. As soon as all the food and water was unloaded — and way too many people got on.

Dr. Stieg: And that was the problem — it was overloaded and it crashed.

Alissa Rubin: Right. It crashed. It went up about seven meters, eight meters maybe. We don't know exactly. And then it fell.

Dr. Stieg: So what's your recollection of that? Do you have any recollection of that immediate event?

Alissa Rubin: The immediate moment of contact, I don't remember. I remember that it began to tip. The pilot righted it a little. And then it began to tip again. And I was waiting for the crash and I never experienced, in my memory, the crash. I've regained a lot of my memory of the event, but not that.

Dr. Stieg: So what's the first thing you remember?

Alissa Rubin: I remember coming to and thinking I'm alive and I also thought I have to get out of here, but I didn't really know how to do that. And finally I thought, I think if I just hoist myself up using my arms, I can do it, and then my arms couldn't do anything because both my wrists were crushed and I looked down and I didn't know why they weren't working.

Dr. Stieg: And fortunately, there were some people there to at least help you in a first aid fashion. The photos I saw, it looked like you must've had a large cut on your forehead.

Alissa Rubin: I had a lot of cuts. I had, I think when you saw me they'd put about 15 stitches in my face, but there was no one on the mountain with a first aid background. Very luckily there were some, some guerillas who were there who were fighting with the Yazidis. One of the men took off his scarf and he tied my wrists, so they were sort of immobilized and I could never thank him enough for doing that because the pain was excruciating.

Dr. Stieg: So fast forward then — I presume a, an emergency helicopter came, picked you up and they took you directly from there to where?

Alissa Rubin: Back to the Iraqi Army base from which I had left where I was put into, I think it was sort of like a minivan on the floor. I mean all of this was very primitive and we bumped over. Uh, it was horrible.

Dr. Stieg: And this, you remember this?

Alissa Rubin: I remember it was awful. Yeah, I mean I remember I came in and out.

Dr. Stieg: Excruciating pain?

Alissa Rubin: Excruciating pain everywhere. Wanting to sleep and being afraid to sleep because I was afraid that something bad would happen in my brain and maybe I wouldn't wake up. And then they took me to a trauma hospital and they were worried about bleeding in my brain and they did an MRI and they decided I could travel somewhere and then they put me in a taxi, I guess. And the taxi was driven to the border and then I was transferred into another taxi for the other side of the border, right? I mean it was awful. I came to kind of came in and out of consciousness. I don't remember all of it.

Dr. Stieg: Sophisticated enough that they had a, had an MRI scan, which is great, but then taxi transport...

Alissa Rubin: Then they very kindly, the Turkish government, they were medevacking the Yazidi member of Parliament to Istanbul and they medevacked me as well.

Dr. Stieg: And your health care experience in Istanbul was positive?

Alissa Rubin: Yes, it was very, very positive. I was in the American hospital, people spoke English. But I have to say I had only one thought I was able to hold onto at a time and that thought was that I, I wanted, I wanted to have written an article out of this experience. I went there for a reason and I felt horrible and guilty that and terrible that somehow this had happened and I, I had to do something before I completely fell apart cause I, I couldn't really think in any coherent way to be honest.

Dr. Stieg: I guess I want to dissect this a little bit. You were having terrible symptoms, but you still have this bond, emotion, emotional sense that you wanted to accomplish what you wanted to accomplish. What were the, what were the symptoms you were experiencing through this? You said you were fading in fading out, afraid of going to sleep, afraid you weren't going to wake up

Alissa Rubin: That and an enormous pain because they hadn't treated anything and they were afraid of giving me morphine because of the sedative effects and the potential damage I think that could cause. I had a punctured lung and I, I couldn't have walked if I wanted to. I mean my, everything kind of collapsed.

Dr. Stieg: What would you say about your thought processes? Did you feel like you were oriented and you could...?

Alissa Rubin: No, no I didn't. I, I just felt like I was holding on and I didn't have a good sense of time. I remember that. I remember I'd opened my eyes and one of my colleagues came with me and he was there and then I'd open my eyes again a little later and he wouldn't be there. And I wouldn't know if it had been a little time, a long time. It was a blank.

Dr. Stieg: And then we fast-forward a little bit and we get this phone call that there is a an American journalist over in Istanbul and they ask if we would be willing to accept you and transfer because, in doctor-speak you had a moderate traumatic brain injury. That's obviously more serious than a mild traumatic brain injury, which is more commonly known as a concussion. But the worst problem was all the other injuries that you had, the wrist fracture, the punctured lung, you did have multiple facial fractures and all these lacerations.

Alissa Rubin: And then my nose was quite broken and the septum was sort of askew.

Dr. Stieg: Yeah, and then the thing that was really not addressed at all, certainly in the acute phase was the lingering effect that this had on your brain in terms of how you're functioning. And that's why I'm totally surprised that was — was it in the Istanbul hospital bed that you still wrote an article?

Alissa Rubin: I didn't write it. I dictated it to my colleague Rod Nordland. That was the only way I could do it because I couldn't use my hands at all. I mean, they were completely bound up, they were broken, they were in shooting pain. And so I knew I wanted to do this because I didn't know how long I'd be able to do it for. So, and I also really felt strongly that the pilot was not incompetent. He was a person of great heart and he had died doing this and I felt like, why should I have lived when he was, he actually saved a lot of people. Those people, almost all, lived. A couple of other people didn't, there were, I've gone back now and tried to trace everybody. So I think a total of probably three or four died, but the others survived.

Dr. Stieg: Obviously you knew that you had injuries and you ate and you know when we all get sick, we realize we're not at our, on our A game. But when did you realize that it wasn't only that you weren't on your A game, but there is actually some changes that occurred as a result of this crash?

Alissa Rubin: It was after I got home. I was lying on the bed I grew up on basically and I took down a book of, I still remember it was Chekhov's short stories and I thought I'll, I'll just read these. I can't really remember them now. Anyway, I, you know, I read them in high school, I was reading and my mother had put down the book. My mother came in and she said, "Oh, what are you reading?" And I didn't know what I had been reading. I had no memory of what I had been reading. It was like there was an eraser in my brain coming behind each word and wiping it away. And I was terrified because that's all I do. I read, I think about what I've read. I come up with questions and I go out and talk to people and then I write it and if I can't read and retain anything, what use am I? And there was one other thing that happened. I went to get my first hand therapy for to recover and I got to the counter where they check you in and the woman said, who are you here to see? And I said, "I don't know." And then she said, "Well, why are you here?" And I thought, "I don't know, why am I here?" And I was, I burst into tears.

Dr. Stieg: You've won enumerable awards for journalism. You're an incredibly accomplished individual. So I can just imagine what was going on in your mind or what wasn't going on—

Alissa Rubin: I just felt like I was a child, you know, and didn't really know where to go to sign up for a class or something. And so I remember I came in to you and I was very, I felt very strongly that I had to go back to work. And you said, "Well, I can write you a note, but you will fail if you go back this soon. You're not ready." And I was really upset and I think I began to cry there too. And that was actually very useful. We both recognized that there was something more going on for me. I mean, there was not just the actual injury, but the emotional reaction to the injury and, and how that pulls you down because you're not yourself anymore.

Dr. Stieg: What people need to understand is that as a result of your injury, you didn't have a specific blood clot or some focal injury to your brain, but what had happened was the connection fibers between the various regions of your brain had been disrupted. And like any other organ, it takes time for those things to improve and at the time of that office meeting, I had two goals. Number one was to get you to realize that you weren't there yet because I knew from your hospital bed you had told your editor or your boss that I'm going back to Baghdad, which I was totally in favor of, but not just then. So I was hoping to give you the realization of your problem, but then also the permission to cut yourself some slack because that's not something you do for yourself normally. Can you characterize that, you know, after we had that conversation, some of the emotional repercussions of the feelings that you were having?

Alissa Rubin: I guess I was glad that you were blunt, but angry that you were blunt because I really felt like I didn't have a lot of time. I thought, if I'm away too long, somebody else will take my place. It doesn't matter. We are all fungible and I, you really know that as a journalist — that's why the system works. I felt terribly precarious emotionally and also in terms of what my future would be. I have to say you were helped a lot in the advice you gave because I happened to have a very close friend who also came to see me at the same time, who's also a doctor, who also said, you, you're depressed and you need to do something about this.

Dr. Stieg: It was clear to me in many people around you that you were suffering from depression and probably from post traumatic stress disorder. I really look forward to talking with you about this in more detail.

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New York Times journalist Alissa Rubin talks with Dr. Stieg about the cognitive and emotional effects of her injuries, and the treatments that helped get her back to work and to her life.

Dr. Stieg: Hello, I'm here again with Alissa Rubin and we were talking before about her trauma and the subsequent events that resulted in depression and post-traumatic stress disorder and I wanted to pick up from that area again. Did you recognize that you were depressed or did somebody have to tell you that?

Alissa Rubin: I recognized it but didn't want to admit it to myself even, and I think many people are depressed and have different ways of dealing with it and some people retreat and some people work and I am someone who works for me. Work is a wonderful antidote to anytime that I feel down at all, you know, I start to do a project, I'm writing, I, I'm exercising, I'm maybe taking long walks and it dissipates. And none of those things, none of the remedies that I had recourse to in my daily life that have worked quite well for most of my life worked for me because I couldn't physically do them. I could maybe walk, but I couldn't do my work in the way that I used to.

Dr. Stieg: Was there a stigma for you about the concept of depression or was it just the fact that you're just an a type A personality and gosh, I'm going to lick this?

Alissa Rubin: No, it was that it felt more profound than that I have to say because it had a physical origin and I had been very, very excited. I can't tell you how excited when I got the visa to go to Baghdad and was able to help in this incredible story from a journalist standpoint, but also a moment when you can bear witness to atrocities. That's, that's the whole reason you do this kind of coverage. And that had been taken away from me. I felt very unfairly and then my body had betrayed me and my body had never betrayed me that way before where, you know, I was alive but I couldn't do what I had set out to do. Usually mind over matter takes you a long ways and so I, I did understand what was happening. My, my father was a psychiatrist and I didn't feel like depression was a terrible thing to admit to. I felt like most people should admit to it more and deal with it and then be able to have productive and happier lives. But I didn't want to admit it because this time I felt like, I knew how to have a happier life and it involved running and working and thinking and I couldn't do those things.

Dr. Stieg: Did going to see the psychologist and beginning the cognitive remediation — did that help you gain insight into this and how to deal with it?

Alissa Rubin: Yes, it did. And it was something I really didn't want to do at that point. I'd seen a lot of doctors. I'd had so many tests and MRIs and CT scans, and I remember when you wrote down her name, I just thought, Ugh, not another one. And I went to her and I remember the very first session she said, well, what exactly are you experiencing? And I said, well, I'm trying to work a few hours a day, which I had been told I could do. And after about two hours or so, I'm exhausted and I can't keep going. And she looked at me quite sternly and said, "Well, you shouldn't be trying to work for two hours. You can't do that. You should work for about 40 minutes and then take a five minute break in which you do not do anything. You don't look at websites on your computer, you don't sleep, you don't do anything." And that was a revolutionary idea to me and I was extremely doubtful about it because I thought, how can you not do anything? I mean you could clean, or you could, there must be something I could do. And that the whole point was not to do anything.

Dr. Stieg: That's something many Americans should learn is how to be bored and do nothing for a period of time in their life. Now did this, your initial reaction was obviously revolt, but obviously you came to terms with it.

Alissa Rubin: I did because I made a decision and I remember quite clearly making it and I thought, all right, I don't know this time, what's going to work. So I will do everything even if I don't like it. And you had recommended this, you had recommended seeing a psychopharmacologist and seeing if you know some kind of antidepressant would help. Even a low dose, whatever would work. I do think it had some effect.

Dr. Stieg: I just, I feel compelled right now to, to make this pitch that people need to really understand the complexity of the brain and it isn't solved by just one physician and that's why, I as a neurosurgeon, started getting you involved with these neuropsychologists, the neuropsychopharmacologists and the physical therapists because they were working with your hands and helping you with your exercise and all of these emotional, physiologic and psychologic issues obviously come together in your brain and it was important to get you to work on each one of those individually. But having it done in a coordinated fashion to facilitate and expedite your care. You're an example of how that worked.

Dr. Stieg: Where was your family in all of this?

Alissa Rubin: Well, I think my family was not particularly engaged. They supported whatever I wanted to do in a general way. My husband works in Europe and he was in Europe working. My mother was around, she's in her eighties and so there's a limit to what she could do, but that was actually probably fine because she's a very, she was extremely consistent. She was no different than she has been my entire life, which is, you know, she'll occasionally bring you a cup of tea and she'll be happy to talk with you, but she's not going to be terribly involved.

Dr. Stieg: What doesn't kill you makes you stronger, huh? *laughs*

Alissa Rubin: I knew that it mattered to me to go and maybe more than anyone else in my family. She's always respected that and always been very realistic about it and I am very grateful to her for that because lots of parents might not have understood that. My sister was working, so I didn't have a real family support network, but I did have a couple of friends who were enormously supportive, and... I was tired every day. I was doing physical therapy five days a week because I had different parts of me that didn't work and I had a terrible hematoma, which was totally benign, but it made it hard. It hurt and it made it hard to walk because it was where it was. But I was going to say the other thing that the cognitive therapist taught me was something that I really use every day. I've used it already today. It was that you tend, I think for whatever reason, when you've had this kind of brain injury to start to do several things at once, you're very unfocused and I would be really interested to hear why that is because I still don't understand it. So I would, I would start an email and then I would think something like, Oh, I need to write Dr. Stieg or I need to write Ann, or my cousin Prudence's birthday is coming. And I would open another email and then another and I would soon have three, maybe three emails open, and something I was reading on the screen and get none of them finished and be exhausted.

Dr. Stieg: You'd never had attention deficit disorder.

Alissa Rubin: Not to my knowledge and I was puzzled and she said, well, when you feel the impulse to open a second email, have a notebook next to your desk and write down whatever the item is that you need to do. So you're reassured that you have it anchored there. You will not forget it and then complete one task at a time. And I now do that and I now prioritize my emails in a somewhat obsessional fashion, but, but that continues to work and it's, I think that's a little bit leftover attention deficit disorder that I will have to discipline myself to work with for a long time or maybe everyone has that. I don't know.

Dr. Stieg: You're more complex because of the injury you sustained. It's a little bit of attention deficit, but it's also just a memory disorder and that has to do with the particular area of your brain that was injured.

Dr. Stieg: Was it during the cognitive remediation you were going through, you realized that you were also suffering from post-traumatic stress disorder?

Alissa Rubin: I would not have thought of it as that because I didn't have a lot of what I've seen in post-traumatic stress because because of having been a Bureau Chief in war zones. I've seen symptoms, not necessarily in soldiers but even in our own journalists who are out with troops a lot. You see the effect of the stress and I, I wouldn't have defined it that way. I think that what I had had was memory loss of the most upsetting moments of the accident.

Dr. Stieg: Which would be a stress and what, I actually learned something in preparing for this and that you went through something called EMDR, eye movement desensitization and reprocessing that you must have read about this, thought about it, and elected to do it. Or—

Alissa Rubin: Actually the friend of mine who encouraged me to listen to you on the question of, perhaps needing cognitive reconstruction and some kind of low-level antidepressant also recommended that I see someone for this. She said, you know, it's very interesting. I know some people who do it in New York who do it very well. She's a psychiatrist. She gave me a name and I called the person and I really liked the idea of it because it wasn't a commitment to long-term therapy. It wasn't what I thought of as something where, you know, I was going to go back to France or Baghdad or Afghanistan and you know, I'd be interrupting some process — my father had done, you know, everything from short term to psychoanalysis. I didn't really want to do that. I didn't want to go through that kind of thing. I wanted a quick fix.

Alissa Rubin: And so it appealed to me that it was something that you could do in a — you can't say how many sessions, cause everybody's different but three to six let's say. And that it had been used quite effectively and you know, sort of the post-September 11th periods and it was remarkable. You retell what happened and something and I could not, I don't know that the literature explains it, but something happens on the second or third retelling and things surface that didn't surface the first time. And I had a memory that surface that was very, very helpful.

Dr. Stieg: You come to terms eventually with what happened?

Alissa Rubin: Yeah. And you don't feel, I don't know, you don't feel upset afterwards.

Dr. Stieg: And what's important for people to know is that the, it's been espoused that this is about 80% successful in patients. So it seems to me one of the major hurdles for people like you or anybody with PTSD is just accepting the fact that they have this inner turmoil and seeking help. And there are very good ways of getting help.

Dr. Stieg: It's remarkable to, to watch how the brain works because by retelling it, you see, you see how you've pushed something down.

Alissa Rubin: What the thing that I remembered was that after I had become conscious in that in the helicopter, I suddenly — everything went black and I couldn't see. And I thought, "Oh my God, I'm blind and if I'm blind, what will happen?" I can't do anything anymore. I, I would rather be deaf than blind. What a horrible thought, you know? And that was, it was so terrifying and I felt my whole life was sort of stopping before me. Yeah. I wasn't dead, but so what, I couldn't see anymore. Well, what had happened actually is I had a lot of blood and it had congealed over the eye and coagulated and, and somebody pulled it open after about an hour and a half and I must've started from the light and they said, "Oh, she can see."

Dr. Stieg: I think it's important also, to say that, that you've gone through the psychology, you've gone through the, the EMDR and you've gone through using some medications and physical therapy. All of these are exceedingly important and they all kind of come together in you as a person. You still have some symptoms and I was wondering whether you could describe — what are the workarounds that you're using now to do what you're doing and you're working at the computer. You'll write yourself little notes.

Alissa Rubin: I do. I use a lot of those cognitive disciplines. You know, keeping notes when you're working. Keeping notes, really whenever you feel you might forget something and therefore you're going to start something else. I also have tried when I'm not like when I do take a break, you know, if I'm feeling like I'm losing my focus when I'm writing, I'll try to stop myself. Now what's really hard is to not do something, you know, look at some article I've been wanting to read or spend that time buying some item I need to buy online or whatever. But I, I'm aware of the value of leaving blank space.

Dr. Stieg: Did you have to come to terms with these workarounds? Was there an emotional aspect to it or is it just you realize that it's good for you so you'd do it?

Alissa Rubin: No, I think what helped me is that I, I actually feel, and I remember discussing this with you, that I think more sharply now than I used to, and it may be that I think a little slower and that has actually made me more precise because I'm not scattering myself so much. So I feel like when I write a sentence, I know more clearly what I want to say. And it may be because I'm not trying to do three things because I now acknowledge I can't do three things at once. So it might be a skill that could be useful to people who haven't had any, haven't fallen out of a helicopter, um, uh, or had some other... But I mean it's, I don't know whether the brain can really multitask and maybe it, it actually wants to focus. You can answer that.

Dr. Stieg: it functions best if it focuses. And I think multitasking is, is an overused term. I think we can multitask doing simple things, but if it comes down to writing a Pulitzer Prize winning article, you can't do that. Thinking about two or three other things, you've gotta be focused, you mentioned a little bit about your headaches. Those are persistent, controlled with medication, controlled with mindfulness, or how are you doing that?

Alissa Rubin: I have never found mindfulness really that helpful. I can barely do my five minute breaks when I need to. I'm, I'm not a very good person at the Zen level or which I, I wish I were. Lots of people seem to get a lot out of it, but that's not, that's not who I am. I really control it with, with medication taken. When I feel it happening, sometimes I'll think it's kind of on the edge and I'll lie down for half an hour in the dark and it'll subside and then I won't need to take the medication. But it is something that is more frequent. I can't say that it follows a pattern. I think like a lot of migraine sufferers, I know there are certain triggers for it. I avoid those triggers completely. Um, I know that wine for instance, is a trigger very sadly, and I just hardly drink at all anymore.

Dr. Stieg: I always appreciate it when you send me the bottle. *laughs*

Alissa Rubin: Well, so I think that's the most important element is—

Dr. Stieg Are you going to do anything differently when you go back to Baghdad? No helicopters?

Alissa Rubin: No helicopters. No, I haven't. I have to say I've been in lots of planes since the accident. I haven't been in any helicopters, but I am very careful not to promise my family that I'll never go into a helicopter because I can envision situations where one might need one. But I do think that disciplining myself to follow all those cognitive rules is probably something I'll need to do for the rest of my life and they're not really burdensome. I think you can see them as actually helping your brain. I don't know if I want to say, be healthy, but do what's best.

Dr. Stieg: It's been an absolute delight spending this time with Alissa Rubin. It's a really, every traumatic brain injury is obviously a specific story, so we can't, but your story is one of reconstruction and hope, and it also highlights the, for me and I hope for anybody with traumatic brain injury, the intensity with which one has to go at reconstruction, the levels that you went to in terms of the cognitive remediation and the EMDR and the psychotherapy and the medications and the physical therapy. All that comes together and for you who I would characterize as a type A, highly driven, motivated individual came to terms with the fact that you, you've got to accept your body's limits and you've done beautifully with that. Thank you for spending time with us.

Alissa Rubin: Thank you for taking the time.

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Dr. Helen Fisher, one of the world's foremost authorities on love, explains what happens in the brain when we experience romantic or sexual attraction, how that changes in long-term relationships, and why anti-depressants can make you fall out of love with your spouse.

Dr. Stieg: You know when you meet someone and the chemistry is right, but feeling those butterflies and hearing the bells isn't really happening in your heart. It's because of hormones and neurotransmitters acting up in the brain, which, as a neurosurgeon, is the sexiest organ in the body. Our guest today has taken the study of love and relationships to a new level of science. Dr. Helen Fisher is a senior research fellow at The Kinsey Institute and Chief Scientific Officer to match.com. She has written several books on the evolution, biology and psychology of human sexuality covering the neural chemistry of romantic love and attachment, including the anatomy of love. Dr. Fisher, thank you for joining me today.

Dr. Fisher: I'm delighted to be with you. Thank you for having me.

Dr. Stieg: One of the things you're most known for is using brain scans of people in various stages of love. Can you describe this research and the neuro activity taking place when we feel that proverbial spark?

Dr. Fisher: You know, I really wanted to know what it was. I mean, people will say, you know, we have chemistry or we don't have chemistry. And I thought, Oh, what does this mean? I think we're talking about romantic love. As you know, Phil, I think we've evolved three distinctly different brain systems for mating and reproduction, sex drive, feelings of intense romantic love and feelings of deep attachment to a partner. So I think what we're talking about is that spark of romantic love, not that feeling of attachment. So that's what I was studying in the brain. And the first thing I did is I actually went through the last, I dunno, 50 years of of biological and social literature, trying to figure out what the main characteristics of romantic love actually are. So once I'd figured that out, what I started doing is I would first interview people for a long period of time.

Dr. Fisher: I mean, you know, as you know very well, these machines are expensive and it's very time consuming. The first brain scanning study we did was of 17 people who had just fallen happily in love. They were madly in love. And what we found in the brain was activity along a whole pathway of the dopamine system in the brain. But most important was activity in a tiny little factory near the base of the brain in the midbrain called the ventral tegmental area or the VTA. And that brain region actually makes dopamine it and then sends dopamine to many brain regions. And that's what gives you the focus, the energy, the motivation, the craving, the obsession of intense romantic love. So we ended up finding that romantic love was drive. You know, I had always thought that with all kinds of cognitive processes you, that we think all kinds of things when we're mad and we feel all kinds of things, lots of emotions, a roller coaster of emotions. But what all these people had in common was activity in this VTA linked with drive. And as a matter of fact, this brain region actually lives very close to brain regions that orchestrates thirst and hunger. So it began to occur to me. My gosh, this has been an ancient drive that evolved millions of years ago in order to enable our, our former relatives. And certainly today giving us the ability to focus on a particular individual, crave that person, be obsessed with that person, think constantly about that person and start the mating process.

Dr. Stieg: I presume that there are animal studies and maybe even humans that have had some kind of a stroke or an injury to this ventral tegmental area to corroborate the fact that if you lose that area, there is a change in that emotional spark.

Dr. Fisher: I don't know of studies like that. The problem is that this brain region sends out dopamine under lots of circumstances. So it's not just romantic love, but it is central to the romantic love experience. And by the way, interlink link with all the addiction centers too. And we also found activity in another little factory down near there called the nucleus accumbens. That factory becomes active with all of the substance abuse and with all of the behavioral addiction. So it's not just the VTA, but it's a whole combination of factories way down in the base of the brain that create the intense feeling of romantic love. But to answer your question, I think it's a very important one. There certainly are animal studies that show that other creatures, when they become very intensely interested in in another that the same brain region becomes active.

Dr. Fisher: I mean the same dopamine system becomes active. As a matter of fact, I think that romantic love evolved out of something that I call animal attraction. And so you know when a, an elephant comes in, a female elephant comes into estrus, she doesn't go with all the males. She locks onto one of them and focuses on them and for about five days they snuggle up and pat each other with their trunks. They show all kinds of sort of affiliative behavior. You can see it in all kinds of animals. I've read about over a hundred species, but they have found under — in two species: sheep and in little prairie voles like a field mouse that when a female or a male becomes extremely attracted to a specific other partner that use — find the same kind of activity in the same basic region. So we do have some animal studies now showing that the dopamine system is this particular pathway, becomes active not only in human beings, but in other animals.

Dr. Fisher: The real difference is that in other animals, they're not composing poems and songs and stories and operas and plays and ballets 

and have myths and legends. And love magic that humans do because of course we've evolved this big cerebral cortex. And of course they don't feel romantic love for as long as we do. I've done studies that found that some people can remain in love, not as loving, but in love with a partner for two to five years. And in some partnerships it'll keep coming back. That feeling will keep coming back for years and years into the relationship. And of course when a prairie vole or a sheep becomes instantly attracted, it only could be for 30 seconds or you know, five days depending on the species. So what we've evolved is a much stronger feeling, a much longer duration of the feeling. And of course with our big cerebral cortex, enormous number of artifacts that come from this basic feeling. All of our poems, stories, et cetera.

Dr. Stieg: Well, so what I found interesting in your book is that you stated that individuals that have that long term attraction, the same area lights up almost equivalently. And talking about the three separate stages that we go through when we connect with someone and move forward in a relationship, you referred to it earlier, the romantic, the sexual drive and the bonding. What happens during those stages?

Dr. Fisher: Well, actually, you know, I'm not even sure I would call them stages. I just really think that they are brain systems. So for example, you can fall madly in love with somebody before you've ever had sex with them. You can feel deeply attached to somebody in the office or in college or in your social circle and years later you fall madly in love with them. Or you can start with having sex with somebody and then trigger feelings of attachment. Or you can start having sex with somebody and then move into feelings of mad, romantic love. So I see them more as brain systems than as stages. But I do think that eventually people do settle down into a sense of real deep attachments and these three brain systems really are different. They interact with each other, but the sex drive really emanates from activity in the hypothalamus and the feelings of attachment to a partner is linked with feelings of cosmic union. They're different feelings. You behave differently, you think differently, you respond differently to the person and of course with each one of those different kinds of feelings, you're going to have different brain activity. So these three brain systems really are distinct. I think that most people can pretty easily distinguish between whether they are in love with somebody or whether they just want to sex with somebody, that kind of thing. Or whether they feel deeply attached. We have the feeling that we, we know what we're feeling when we feel romantic love. It's very distinctive feeling.

Dr. Stieg: Is this a little bit like the Kübler-Ross death and dying? Can you have a longterm relationship and skip or omit one of those three phases?

Dr. Fisher: Yes. As a matter of fact, I have run into three people. All three of them came up to me, two men and one woman and they all said, you know Helen, I never understood this feeling of romantic love. All three were happily married, all three had adult children. All three basically said, you know, I never got it. But you know, when I read Romeo and Juliet in college, why would you do that? But all three of them in their fifties fell madly in love with somebody other than their spouse. And all three of them said to me, now I get it. Now I understand what you're talking about. All three of them stayed in their marriage. They went, all three of them went maybe a couple of years into the romantic love and then left that relationship. And it was always secret in all three cases and went back to a full relationship with their spouse.

Dr. Fisher: So there's some people who feel it all the time, fall in love quite regularly. Other people who have only fallen in love a couple of times in their lives. Men fall in love more often than women do. And I think because they're so visual and they also fall in love faster than women do because they're so visual and men are two and a half times more likely to kill themselves when a relationship is over. So, you know, I've been trying to tell the women's magazines for, I don't know, 30 years that men love and indeed they're very passionate, not only in America, but everywhere I've looked in the world.

Dr. Stieg: Clearly love is an emotional interaction, but it really helps to demystify some and debunk some of the stories that people throw around and really gives credibility to the way an individual may feel about or towards another individual. When did you first get curious about the biology of love?

Dr. Fisher: First of all, I'm an identical twin and I thought to myself, if there's any part at all of human behavior and feelings that could have a genetic and biological component, it must be in our realm of love because as Darwin said, if you have four children and I have no children, you live on and I die out. So the game of love matters. It matters to survival. And I thought to myself, well, maybe this is something that must have evolved and have some genetic and hormonal and components to it. I did not start with romantic love. I started the fact that we are an animal that forms pair bonds. You know, 97% of mammals do not pair up to rear their young and people do. And I want to know why the human female lost a period of heat, why we can copulate all month long, and why we form pair bonds, monogamy — mono means one and gamy means spouse. It doesn't mean a fidelity to rear our young. And then one day I was walking along in Greenwich Village by myself. I remember exactly what time it was of day and it was at 3:00 PM in an autumn afternoon. And I thought to myself, Hmm, if we're an animal that's driven to form these pair bonds, and I've certainly felt romantic love many times, maybe I could look into the brain and see what the brain chemistry is all about. And of course I didn't know much neuroscience. They don't teach that in graduate school, in anthropology. So the first thing I did is I bought an awful lot of books on the brain. I love brain architecture and physiology. So it was very easy for me to just pour into that. And then I began to think, well, I'll put people in brain scanners and see what I can find.

Dr. Stieg: You mentioned it earlier about love being a little bit like an addiction and I often marvel at individuals that have been married four or five times. How they have the capability and the endurance to do that, just falling in love. Does it trigger the same brain activity as an addiction?

Dr. Fisher: Yes it does. And in fact, you know, having finished my first brain scanning study of people who are happily in love, I began to think to myself, you know, who cares about this? I mean, this is always a lovely thing if the other present returns the love and it works out. The real problem for the individual, for the family and for society at large is when people get dumped because that's when they dock us, up in the clinical depression and kill themselves or even kill somebody else. So I began putting rejected people into the scan and we put 15 people into this scanner. It was then that I began to think, this has got to be an addiction. It's got so many of the traits of addiction. The obsessive thinking about it is a lot like drug addiction. They — the willingness to do dangerous and inappropriate things to get your drug, which is the person, your willingness to change where you live, where you work, all kinds of problems. I mean, when you're rejected in love, boy, what people will do is incredible. So when I, I thought to myself, okay, maybe we'll see in the brain activity in some of the basic brain regions that are associated with all of the addictions, all of the substance addictions like cocaine and heroin and alcohol and nicotine and all of the behavioral addictions like gambling or food addiction. So anyway, I started looking in the main factory in the brain, also close to the, in the basal ganglia, which is something you would know of course. But, uh, near the base of the brain, I find activity in particular brain region called the nucleus accumbens. And that brain region becomes active in all people who are addicted either to a substance or a behavioral addiction. And then we went back to our people who were happily in love and sure enough, by a different mathematical mechanism, we were able to establish the same brain region linked with addiction. The nucleus accumbens becomes active not only when you're rejected in love, but also when you're happily in love. So actually I'm trying to change our understanding of addiction. I think there are some addictions that evolve for reproductive evolutionary reasons. And so I think romantic addiction can be perfectly wonderful when you're madly in love with somebody and it's returned, and to see appropriate person and perfectly horrible when you've been dumped.

Dr. Stieg: What will be interesting is we are developing surgical techniques for refractory addictions and in thinking about it, we'll also have to then look at how those patients respond to love situations in the future.

Dr. Fisher: That's really interesting because one of the things that I worry about, and you're a neurosurgeon, so I wrote a piece for the MIT Press for a book in which I suggested — hypothesized that these are all the people that are taking these SSRIs, serotonin boosters, everything from the older ones like Prozac and Paxil to the newer ones like Lexapro. They're driving up the serotonin system in the brain. Generally, most of the academic literature indicates that when you drive up the serotonin system you are, it's a kind of negative correlation with the dopamine system. You're driving down the dopamine system and perhaps dampening your ability to feel intense romantic love, and I wrote this article about it and once a week I get a call or an email from somebody around the world who's read that article says, you know how, "I was madly in love with her? We were been married 11 years. We've got two small boys. She wasn't doing well in school. Doctor gave her an SSRI driving up the serotonin system and six months later she came and she said, I'm not in love with you anymore." You know, these drugs do dull the emotions, which is perfectly good. It's important to do if you, if you're really struggling, but the problem is people stay on them and I really do worry that that is going to dampen their feelings of romantic love. So when you do your experiments, it will be very interesting to see if you kill some of the addictive process to one kind of drug like alcohol or nicotine, you're going to also dampen a person's possibilities to fall in love or stay in love.

Dr. Stieg: That's why I think it's so important when people are being treated with polypharmacy for their psychological issues that they really need to work with the neuropsychopharmacologists who who I believe understands best the interactions and implications of taking those drugs.

Dr. Fisher: I completely agree with you. I had a girlfriend who, she's been married for 50 years and you know she got a bad burn in her kitchen and she was in the hospital for almost a month and they then gave her all these SSRI and she said to me, she said, you know, I don't want to have sex with my husband anymore. I don't really care about him anymore, and I was able to inform her, at the very least, I think doctors could say, keep an eye on, for a change in your feelings, for your partner and for your children and for your job and for your parents instead of keeping an eye on the fact that, I mean we may be killing this addiction to nicotine, but you got to make sure you're not also killing your addiction to a sweetheart.

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Dr. Stieg talks to biological anthropologist Helen Fisher about the four hormonal systems that drive our relationship styles, and how they can predict whether love will last.

Dr. Stieg: Earlier you mentioned, you know, the phases of romantic love, sexual attraction and bonding and the different brain regions that are activated during those components of being in love. Do those regions of the brain crosstalk and do they balance each other out?

Dr. Fisher: Yeah, it's a great question. They definitely crosstalk. Now, for example, when you fall madly in love with somebody, you're driving up the dopamine system in the brain, and dopamine has a positive correlation with the testosterone system is just you drive up, go. I mean, you're likely to be driving up the testosterone system too. And this is why, you know, madly in love with somebody, three days ago, he was just a nice guy in the gym or at work or at school or in your social circle, and all of a sudden everything about him becomes sexual. The way he laughs, the way he gets off the bus, the way she twirls her hair, everything becomes sexual. And it's because as you fall in love, you've triggered not only the dopamine system that is activated, the testosterone system and the sex drive. The reverse can be true too. Most liberated Americans have gone to bed with somebody who they were not in love with and never did fall in love with them. But it can happen. And the reason is because when you have sex with somebody, any stimulation of the genitals can drive up the dopamine system and the brain and trigger and push you over that threshold into falling in love. And then with the orgasm, there's a real flood of oxytocin and vasopressin linked with feelings of attachment. So one of the things I say on the podium is casual sex is not casual. Things happen in the brain. So that my business to tell people what they should and shouldn't do. But as I go in to casual sex, it's possible that I could fall in love with this person or I could feel deeply attached to this person. Am I willing to take that chance?

Dr. Fisher: And in fact, I do a lot of studies with match.com not on the match population. It's, I regularly ask the question, have you ever gone into a one night stand? You know, just thinking it's a one night stand and then found yourself going long term and this and turning it into a really long term committed relationship. And every year something like 30% of both men and women say yes, it certainly can happen, but they're not always connected. You can lie in bed at night and feel a deep sense of attachment to one person and then swing into the feelings of wild, romantic love for somebody else and then into a feeling of sex drive for somebody you hardly know. So this leads of course, I mean the brain is very well built to fall in love, form a pair-bond, and raise your children as a team. But it's also unfortunately built for — it the ability to love whether one person at a time, keep attachment for one romantic love for another. And of course real restlessness among among relationships, divorce and remarriage.

Dr. Stieg: A large part of your research has brought you to delineate four separate biologically based groups of people, each with its own host of traits.

Dr. Fisher: Well, but the question — This all started when match.com came to me in 2005 and it was two days before Christmas. I didn't, and they asked me to meet with them two days after Christmas. So I, you know, nothing happens in New York at Christmas, but certainly went. And as it turned out, it was the CEO on down in the middle of the morning and he said, why do you fall in love with one person rather than another? And I said, you know, I just don't know. I don't think anybody knows. I mean, there's all kinds of cultural reasons that you go for one person rather than another. You know, we tend to fall in love with somebody from the same socioeconomic background, same general level of intelligence and good looks and education, religious values and social goals and economic resources all play a role.

Dr. Fisher: But I thought to myself, you know, people will say, we have chemistry as I mentioned, are we naturally drawn to some people rather than others? What is the biological component? Now, people in my field have known for some time that a good 40 to 60% of who you are comes out of your biology. So I thought to myself, what is that part of the puzzle? Are we naturally drawn to some people rather than others? So I went through all the biological literature for a couple of years again and looking for any trait at all linked with any biological system. And I found four brain systems that are each one, just as you mentioned, a link with a constellation, a suite of traits. The dopamine, serotonin, testosterone, and estrogen systems. Now we are all a combination of all of them. These are not buckets, they're not basic categories, but we express some of these categories more than others.

Dr. Fisher: So bottom line is I created a questionnaire to see to what degree you express the traits linked with these four brain systems, the dopamine, serotonin, testosterone and estrogen systems. And then I created a questionnaire, and I put it internationally on match.com and domestically on one of their other sites called chemistry.com and 14 million people have now taken that test and I was able to watch who's naturally drawn to whom for a first date and first dates are important because that's when I think your biology is most likely to draw you to somebody after you get to know them. You think of all kinds of cultural things that you don't like this about them. You do like that, but I think it's actually a pure state, that very first attraction. So anyway, this is what I've found. If you are very expressive of the way to the dopamine system, you tend to be novelty seeking, risk-taking, curious, creative, spontaneous, energetic, mentally flexible.

Dr. Fisher: And the biggest thing in the dopamine system is what they call idea generation. These people are idea people and they're naturally drawn to people like themselves. Novelty-seeking, risk-taking, curious, creative people want somebody like themselves. People who are very expressive of the traits in the serotonin system are also drawn to people like themselves. I think a good example would be Mitt Romney and Ann Romney and these people are traditional. The conventional, they follow the rules. They respect authority. They like schedules and plans. They're concrete thinkers rather than theoretical thinkers. They're cautious, not scared, but they're cautious and they like the familiar. They also tend to be more religious. Actually religiosity is linked with a particular gene in the serotonin system, so these people are drawn like themselves as either I know the main people, the other two types, the highest testosterone and the high estrogen people are drawn to the opposite.

Dr. Fisher: People very expressive of the testosterone system, tend to be analytical, logical, direct, decisive, skeptical, tough-minded very good at things like engineering or math or computers or music is very structural and they are drawn to the high estrogen type, which is a people who, Oh, they're imaginative, they think longterm. They're synthetic contextual thinkers. They're good at reading, posture, gesture, tone of voice. It's a good intuition. They tend to be a nurturing and what we call pro-social, but I do want to stress the fact that we are all a combination of all of them. Now, for example, I've got this new man in my life. He and I are both high dopamine and that works very well. He is very high testosterone and I'm very high estrogen. So in that case, opposites attract, which is very natural. And it was the dopamine we're similar, which also attracts.

Dr. Fisher: So in that way we are both very compatible. He is higher on the serotonin system than I am. Recently we went to the movies and I said to him, I said, "Sweetie, do you happen to have any water in your backpack?" And he said, "Yeah, I do." I said, "Well great, we can drink that in the movie house." And he said, "Well no, we can't. You know, that's not, you can't bring food and drink into a movie house. You've got to buy it at the concession stand." So had I not known that he is naturally a guy who respects authority and follows the rules, I would've might've thought, "Oh, how stubborn and ridiculous." But it's who he is. And along with that, he's also the kind of guy that's probably not going to cheat on me. He's going to follow those rules. He's going to be very upright in many other ways and so what I've really learned is first of all, you got to know where people land on all four of the scales. That's important and then once you know what somebody is like, I don't even agree in the golden rule, you know, do onto others as you would have done unto yourself, I believe in the platinum rule, do unto others as they would have done unto themselves and you can reach them and win.

Dr. Fisher: The original questionnaire was done for match.com and it's a book called Why Him? Why Her? That I wrote this right in there, Chapter Two. You can buy the book, I dunno for six bucks, whatever it is and it's right in there. You can also find the original questionnaire in a lot of places on the internet, including one of my websites called www.theanatomyoflove.com but you can find it on there that, since then, I've actually done the next iteration of the questionnaire, which I think is even better because I added some bells and whistles to it. That is one that I use in business and you gotta pay some money for it, but it's at that my website, neurocolor.com

Dr. Stieg: It seems to me that there may be certain personality types that are more inclined to remain monogamous versus not, or is it really social pressure or is it just natural to remain monogamous or not? What's your take on that?

Dr. Fisher: Well, let's define monogamy first. You know, in biological anthropology, we don't regard it as fidelity because it's a pair bond. Mono means one and gamy, it means spouse, one spouse. It does not mean being sexually faithful to that spouse. But I have looked at adultery in 42 countries and everywhere I've looked, do you find that everywhere in the world? And in fact, we actually know some of the genetics that play a role in it, in adultery. So I think that people are probably a great, many people are predisposed to adultery. And then we think with our big cerebral cortex, I'm not going to do that. I love my wife. I've got a new baby, I've got a great house, but I don't want to ruin either my health, my reputation, or my family or my job to do this. So, you know, we have all kinds of predispositions that have evolved for Darwinian evolutionary reason, but we're not puppets on a string of DNA.

Dr. Fisher: We make decisions in our lives. But you asked the question of which of these four styles of thinking is more likely to be adulterous? And the answer is, I don't know. I honestly don't know. I don't think anybody knows. You know, I've just begun to define this. You know, every other personality questionnaire in the world started from a linguistic studies so they can't go back and validate it by going back to the linguistic studies to prove that they're studying what they're really studying. Whereas mine started from an understanding of brain circuitry and physiology and architecture to make a questionnaire and then went on to do two brain scanning studies to prove that the questionnaire studies what it actually studies. Now I need other people to take that questionnaire and bring it into their therapy community and and have people walk into their office who happened to take it and we see what patterns there are.

Dr. Fisher: This is just the beginning of a new understanding of personality and my hypothesis is that these four styles of thinking and behaving are going to be more predisposed to different kinds of addictions. I wouldn't be surprised if the high dopamine type of person is going to be more likely to be adulterous because they're restless and they're curious and spontaneous and they can get into things that they didn't realize they went to. My guess is that the high serotonin type, because they are traditional conventional follow the rules, they might be more likely to have an attachment addiction where they stay in very bad relationships and don't get out of them because they feel a responsibility to the community and to themselves and to their vows. And it's entirely possible that the high testosterone may do more abandonment rage and do more homicide when when they feel addicted to love and then the high estrogen type may well be more inclined to clinical depression.

Dr. Fisher: But you know, we don't even know what alcohol does to this brain system. I mean, when you're an alcoholic, do you fall in love with everybody because you sensitize this whole brain system, or do you fall in love with nobody because you're so over sensitized that you, you don't reach out. We haven't proven it yet yet with SSRI. How about people who overeat? How about people who get exercise or don't get exercise? I mean, you know, I just hope that I'm still alive to see other people take my data and get an understanding of this personality type so that when somebody walks into the therapy office, when they want to hire somebody, when they want to build a team, when they want to create innovation in the office to use this material in all kinds of ways to understand people better and to get people the help they need when they're in trouble and put them into the right kind of jobs so that they do their best.

Dr. Stieg: Helen, this has been a most fascinating half our discussion and I appreciate your bringing your years of research and knowledge to lessons on the brain. And I think it proves the old adage that when you answer one question, you've created many more.

Dr. Fisher: Can I tell you one more thing? Cause it's so important to me — It's about happiness, you know, and a lot of psychologists will say, what can the brain tell you about happiness? It is just a blank, you know? And they will say there's all kinds of cultural reasons that people create a happy relationship. And I like them all. I mean people will say, don't show contempt, you know, don't threaten divorce. Listen accurately, all very good, but this is what the brain says about happiness and we discovered it. We stumbled on it. We put people in who are in long term partnerships. Average period in the partnership was 20-21 years. These people were all married. They were married longterm. They came into the lab saying, I'm still in love with her or in love with not just loving but in love with this person. We put them in the machine not knowing what would happen.

Dr. Fisher: Well, we did find the same activity in the ventral tegmental area and other brain regions linked with romantic love, but we also found three brain regions linked with happiness. They had taken a questionnaire on marital happiness and these are the three brain regions that become active when you are in a longterm happy relationship. Brain regions linked with empathy, brain region, liquid controlling your own stress and your own emotions and brain regions linked with what we call positive illusions. The ability to overlook what you don't like about somebody and focus on what you do. So the brain and understanding of the brain can add a great deal to psychology. I don't want to wipe out psychology. It's all good. I want to bring to the psychological and the therapy and the addiction community, and the legal, and medical community — data that can help them expand their horizons in dealing with their issues with their clients.

Dr. Stieg: You can find more about Dr. Helen Fisher at helenfisher.com and of course, please visit us at drphilstieg.com with any questions and comments.

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Dr. Stieg talks to psychiatrist Dr. Richard Friedman about the neuroscience of fear: How parents can transmit anxiety to their kids, how some babies seem hard-wired for anxiety, and why a little anxiety is good for you (but too much is like a burglar alarm that sounds all the time).

Dr. Stieg: Today I'm with Dr. Richard Friedman, Professor of Clinical Psychiatry and Director of the Psychopharmacology Clinic at Weill Cornell Medical College. He's also an op-ed contributor to the New York Times. Richard, thank you for being with me today. It's a pleasure. So being a psychiatrist, we're going to have an interesting conversation about some of the more common things that you deal with and as a matter of fact, as a neurosurgeon I have to deal with on a regular basis and I'm happy to start with one where, this week actually, in clinic, I felt like I was more of a psychiatrist because all of my patients were incredibly anxious about their brain surgery and I can't understand why. *laughs* So tell me what's the difference between good and bad anxiety?

Dr. Friedman: If you think of anxiety, like an alarm that's supposed to tell you that there's something that you should pay attention to that might not be good, like a burglar alarm in your house. It's supposed to go off and there's an intruder or there's a danger, that kind of anxiety, which is a signal that there's something either bad in the environment or bad that's about to come around. The corner is a good kind of anxiety because it's adaptive. But what if you feel anxious and there's no danger or to put it in another way, what if you feel anxious and basically the danger is imaginary. There's really no risk. My patients feel anxious for no good reason at all. They come home and they feel anxious, they go out and they feel anxious. They could be in Tahiti and they would feel anxious so they have inappropriate anxiety. Or if you had a house with a burglar alarm, your alarm was being set off by a mosquito. That's a bad alarm. So it's over-sensitive and it's basically telling you there's danger when there isn't any danger. That's the kind of anxiety you don't want to have.

Dr. Stieg: I'm sure a lot of people that have anxiety worry about this. Is it genetic or is it environmental? Is it learned?

Dr. Friedman: So it's both. You know, there are people who when you see them, when they're very young, from the first year of their life, they're reactive. They're more frightened of strangers. They don't like novel situations. You take them away from their parents and they get really upset and anxious. And that's a trait and that seems to be hardwired. And although those kids who have a lot of anxiety and stranger anxiety when they're young, some of them actually grow out of it. A fair percent of them, it's stable. And what you see early on is what you get later as an adult. And on the other hand, you know, the kids learn to be anxious from their parents. You see this on the street, you'd see the parents who's got a kid who's about to cross the street and they grab them by the back of their shirt and yank them back where they're, you know, just looking at their kid, wondering when the next accident's about to happen. They say, no, no, no, no, don't do that because you might fall. So you learn anxiety and it's modeled by your parents, but you have a genetic loading for it to start with.

Dr. Stieg: What do you have to say about pregnancy? There's all this stuff about sitting in putting a little tape of Mozart next to the pregnant woman. Is that, is there any role for anxiety or non anxiety activities during the gestation period?

Dr. Friedman: There's a lot of speculation about this. You know that what happens in your in utero environment to somehow going to set the stage and effect whatever your genetic endowment is, depending upon what your mother listens to and whether you swim or you do ballet or you ride a horse and there's not a shred of evidence for that. The evidence is for all the bad things like being exposed to the flu or you know, having some viral infection during pregnancy does something that's harmful to the fetus. But the idea that you could do something when you're a pregnant mother that will enhance the outcome of your kids. You know, emotional wellbeing or cognitive wellbeing. Well, we just don't know anything about that.

Dr. Stieg: And I'm assuming that the, the extreme of anxiety is a panic attack.

Dr. Friedman: It's one form of really pathological anxiety where it's kind of a, a seizure of anxiety and sometimes they come out of the blue, you know, you could be feeling completely calm and then you go from zero to a hundred miles an hour in five seconds and you feel like you're going to go crazy and die and your heart rate goes up and you can't catch your breath and you go to an emergency room and they say, you know what, there's nothing wrong with you. We've checked your heart out, there's something medically wrong and they discharge you and they got half of it right. And half of it wrong. There is no cardiac problem, but you have a panic attack, which is, you know, a kind of intense paroxysm of anxiety.

Dr. Stieg: The first time this happens for somebody, do they know it?

Dr. Friedman: Almost no, never. They think something, either cardiac is happening, that they're going to die of a heart attack. Or are you going to have a seizure or they're going crazy? It's usually one of those three things.

Dr. Stieg: So they go to the doctor and the doctor tells them that, no, you're having a panic attack. Are they, are they surprised?

Dr. Friedman: They're relieved because usually they don't actually get the diagnosis until they've been seen a few times in an emergency room and sent home reassured that nothing, you know, medically is catastrophic. And eventually they see their family doctor where they see a specialist who says, Oh right, you don't have a heart attack, you haven't had any real cardiac problems and you're not having a seizure and you don't need to see Dr. Stieg. And there's nothing wrong with your brain. You're having a panic attack. It's really common, really common.

Dr. Stieg: Really. How common are panic attacks?

Dr. Friedman: Anxiety is probably the most common complaint in the general population. So you're talking about a lifetime risk of about 18-20%

Dr. Stieg: Is it the, I'm always anxious, that type of person? Or every now and again I'm going to have an an attack of anxiety in my—

Dr. Friedman: Yeah, so it's all forms of anxiety. So it could be panic attacks, could be general anxiety. People who are constantly in the background worried and tense and they worry about one thing and if they don't worry about one thing, they substitute another. And people who are socially anxious and people who have performance anxiety and worry, you know when you stick them in front of group of people, they get really nervous and can't speak. Right. So if you add all that up together, that's about 20%.

Dr. Stieg: So that person, as I see it, they take some Inderal all to get rid of their speaking problems, right? Inderal, being a beta blocker, slows the heart down a little bit. What struck me the other day when I was dealing with this patient was a younger woman. Her mother was there and I was just watching this anxiety-ridden individual. I didn't want to do anything. I was telling her she didn't need to do anything and she just got incredibly anxious about not doing anything. And I was watching the mother kind of play into this. Well, my next question is, does this come on in childhood? Is it come on in adulthood or any time?

Dr. Friedman: there's a peak of anxiety in late sort of adolescents for the kinds of anxiety we're talking about. Social anxiety and let's say panic attacks. The trade anxiety is early. You know, people who are generally nervous and anxious, you can see that in childhood. Okay. Um, and separation anxiety. You see early on when kids have to start going out from the nest and first step to go to kindergarten and first grade and they just get really uncomfortable and anxious and or sick physically. I have a stomach ache. I can't go to school today. And uh, you know, depending upon how their parents respond to them, it totally shapes the nature of their anxiety.

Dr. Stieg: Well, that's where I wanted to go with this is the watching the mother watch her daughter, let's say said as a parent, we all want to think that our children are perfect and we see this anxious trait in this behavior. You look at them, you know, what am I to do as a parent? What's the best thing? Get help right away or should I try to cope with it? With my adolescent child?

Dr. Friedman: Well, the answer actually depends on what kind of person you are. So if you're an anxious parent and you have reasonable people in your family and friends who say, you know, you worry too much, there's nothing wrong with your kid and you're going to make your kid anxious like you, you should back off. So actually it was an interesting study done of the parents of anxious children, the kids who are just generally anxious, and what they found is the mothers who worried about these kids and tried to protect them and shield them from situations that they thought would make them anxious. The outcome in those kids was much worse than the parents who didn't try to protect them. So if you hover over these kids who are anxious, they end up being more anxious. And if you let them get anxious and get exposed to things and get over it, they do much better. And they're less anxious as teenagers.

Dr. Stieg: What is it about the adolescent brain that makes them, you said that, that's the peak. Is there something about their brain that makes them more susceptible? Things like....

Dr. Friedman: Yes.

Dr. Stieg: And that is?

Dr. Friedman: And that is that different regions of the brain develop at different rates. And so one of the regions of the brain that comes online early is the limbic system and the limbic system is the emotional brain in a way that is not conscious. It's primitive and it develops very early in life and is fully functional before your prefrontal cortex, which basically is the part of your brain that allows you to think critically and to suppress impulses and to think, you know, if I do a then B will happen and if I do B then C might happen. And the limbic system is basically your emotional responsiveness and that could be to, you know, anxiety and fear. It could also be to the desire to want to have sex or use drugs.

Dr. Stieg: Based on that, and we know also that boys' executive frontal prefrontal cortex develops more slowly than in girls. It can. I assume then that boys have a higher incidence of anxiety than girls do because their prefrontal cortex is, is more fully developed early on in life.

Dr. Friedman: In some forms of anxiety, they do, actually — they have higher rates of social anxiety as teenagers.

Dr. Stieg: As you said, so if mom and dad are both anxious people probably best that they shouldn't try to cope with their child's anxiety and they should, then you would say get some professional help? Yes. Yes. What about in this day and age where every state seems to want to legalize marijuana? What role does cannabis play in managing anxiety disorders?

Dr. Friedman: That's an interesting question. I mean, we don't know. We worry about kids who are exposed to a lot of cannabis early during, you know, critical brain development and we know that it's associated. That doesn't mean it causes, but it's definitely associated with the risk of certain psychotic disorders like schizophrenia. I doubt it causes it, but it might actually unleash it at an earlier age and people who are genetically prone. As far as anxiety, we don't know. It may be the kids who were more anxious are self-medicating and are more likely to be drawn to use cannabis because it lowers anxiety.

Dr. Stieg: Is therapy or medication the better way to approach dealing with a severe anxiety disorder or person is having such frequent panic attacks that they can't function.

Dr. Friedman: So they both work. But actually it depends on what age they are. So we know younger people like adolescents because of the way their brain is developing and their prefrontal cortex is not yet mature. They actually have a hard time with certain forms of therapy where they're being taught to be unafraid because you need a prefrontal cortex to learn and you know, exposure therapy's not so effective in teenagers

Dr. Stieg: is the basis of all this anxiety. We talked about it being familial in parents and some genetic component, but is the basis of anxiety fear?

Dr. Friedman: The basis of anxiety is a fear circuit that is somewhat out of control and is mismatched. It's got a very strong signal and has got the upper hand and the people with a lot of anxiety have an overactive fear circuit that can't be shut down by their you know, reasoner-in-chief, which is their prefrontal cortex, so there's a mismatch.

Dr. Stieg: And do we have to differentiate between external causes of fear and then there's internal irrational sense of fear?

Dr. Friedman: We do because the people who have anxiety disorders are not confronted by external dangers in order to feel anxious. They feel anxious even when there's no danger.

Dr. Stieg: I read an article that you had written about resilience and it seemed to me to play a little bit of a role in children's response to fearful environments was in Chicago and they were I think exposed to terrifying events and then you found that those individuals are actually more resilient than individuals that grew up in a higher economic class and were never exposed to any kind of fear and anxiety. They weren't as resilient.

Dr. Friedman: So there's two things. One is the idea that you get more resilient by tolerating a certain level of stress and adversity seems to be true up to a certain point obviously. And if the stress and the anxiety is so great that you can't manage or master it, it's probably not helpful and adversive. And that study that was in Chicago was slightly different, which was basically showing a link between how much connectivity there was in the brain between different circuits and being able to control oneself and good health outcomes. So people with more connectivity actually had better health outcomes and better sense of wellbeing than those with less connectivity.

Dr. Stieg: I thought the implication was that a, I'm playing a little bit off the fear, you know, the normal external fear, you know, you're being threatened and so your frontal cortex is somehow regulating the amygdala, the limbic system that you're talking about. And as a result of that, you are more resilient.

Dr. Friedman: No, I think that's exactly right. And the reason you're more resilient is because you probably are making better choices when you're scared. What I'm really trying to get at then is the parenting role in all of this, you know, is a certain amount of fear in a child's life good?

Dr. Friedman: Yes. I mean there's no question that you can't shield people from everyday adversity and it would be bad thing to do it. It's like immunity. You know, the kids these days grow up and their parents are terrified that they should get dirty and they give them bottles of Purell. And what do we see? We see high rates of allergies to things like peanuts, which in my day didn't exist. We played in the dirt, we ate the dirt. You know, we were given levels of immunity because we were exposed to the external world and not told to be afraid of it.

Dr. Friedman: So as a psychiatrist, how are you dealing with these? What I see as these hypervigilant parents when they bring their children in to see me and I'm, I really worry about what we're doing to our children down the road. And then are they going to do this to the next generation?

Dr. Friedman: Yes. I worry about it too. And so I, this is the whole phenomenon of the helicopter parents who, you know, as good as their intent is to be sure their kids grow up happy and healthy and get every advantage in life. It may be that their protective attitude is having the opposite effect because they're less able to deal with adversity. How do we go about getting parents to not be this, as you call it, helicopter parent or as hypervigilant. There's is, is there a movement going on? Like you said, I mean these peanut allergies are everywhere. My kids can't go out to dinner with somebody and we don't have to worry about the peanuts.

Dr. Friedman: Well, I mean there's a role for, you know, professional organizations like you know, the American Medical Association, the American Psychiatric Association and you know, leaders in the field who basically can say, look, we see a sort of change in social attitude and you know, we have data to show us that it's not a great thing. On the other hand, how did this come about? What are the social forces that made helicopter parents in the first place? It's probably related to certain social classes. You know, it's an upper middle class phenomenon of, you know, parents who want to be sure their kids are going to get the competitive advantage. Why? Because there's more competition, right? More kids are applying to colleges and more applications per kid. It's a natural reaction.

Dr. Stieg: Which creates more fear and creates more anxiety, a vicious cycle. As you said, if the parents are anxious, they probably shouldn't try to deal with it. As a professional that deals with this. Is your first choice some kind of verbal therapy or do you immediately go into drugs and if there are drugs, what are the drugs that you use for dealing with anxiety and anxiety that stems from an abnormal fear?

Dr. Friedman: So if it's something that is not so severe in the sense that it looks like it's learned and it's easy to intervene and convinced the kids and the parents to change their behavior. Not saying that's easy. You would intervene with some counseling and therapy and basically, you know, the problem might be that the parents may be responding to an anxious kid by trying to protect them. It could be. The parents are so anxious. The kid is learning it from the parent, and you have to spend some time with them and figure out which it is, and then intervene. But let's say it's the kid who's really got anxiety, so they're, you know, you might use some cognitive behavior therapy, and the best biological treatment for anxiety is a antidepressant in a serotonin reuptake inhibitor family like Prozac and Zoloft and Selectsa and Lexapro, and these are drugs that increase the function of the neurotransmitter serotonin in the brain. That lowers anxiety. It also makes depressed people feel better. So it does both.

Dr. Stieg: We'll be continuing this fascinating conversation in our next episode. Please join us.

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Dr. Stieg talks to psychiatrist Richard Friedman, MD, about depression and PTSD: How they are different from sadness, how the brain actually changes when someone is depressed and when they come out of it, and how therapy and medication work. Plus... identifying those at risk for suicide, and getting them help.

Dr. Stieg: I'm back again today with Dr. Richard Friedman, Professor of Clinical Psychiatry and Director of the Psychopharmacology Clinic at Weill Cornell Medical College. He's also an op-ed contributor to the New York Times. Last time we met we were talking about fear, anxiety, and I'd like to change the focus now and talk a little bit more about depression. We all get sad. What's the differentiation between sadness and depression and when does it become a clinical disease?

Dr. Friedman: So everybody feels sad and everybody gets upset and usually it's because so

mething happens that is upsetting. You know, you have a loss, you lose your job, you break up with somebody you love, your house burns down, you know there's stress. And the difference between a normal reaction to loss is sadness, but depression is something different. Depression is a syndrome. It's a syndrome in which somebody develops a pervasive sense of loss of pleasure. And the core thing about depression that most people don't understand is it's primarily not about feeling sad. It's about feeling the absence of pleasure and the absence of feeling. It's a negative state that has these associated other symptoms like change in appetite and difficulty sleeping in loss of libido. And then one thing that sad people do not experience and that is a loss of self esteem. People who are sad basically can tell you, I'm sad because this happened and I'm sad because that happened. And if you ask them, yeah, but do you feel critical or bad about yourself? The answer's no. There's nothing wrong with me. The world did something, I lost something, I feel fine. My self esteem is preserved. People who are depressed have an impairment in self esteem. They lose their self esteem and they think that things are never going to get better and they have distorted thinking and then they have suicidal ideas and they make suicide attempts and commit suicide.

Dr. Stieg: I'm interested when, last time we spoke about anxiety and fear, and addiction — you mentioned the need for pleasure and the dopamine. And now again, when you're talking about depression, there's this absence of pleasure in somebody's life. And I'd like to link it to the concept of boredom and how we deal with boredom. And as I was reading about boredom, I was thinking, I love being bored. I liked just the absence of anything. And there's just this feeling of being alone and quiet. And I don't think enough of us know how to be bored. But when I was reading about it, it also went into there's some loss of pleasure and that's why the person is bored and they're waiting. They don't know what for, but they're waiting for something to happen, which is kind of like what you're saying about depression. You know, it's, these are the world's fault. Explain that to us.

Dr. Friedman: The difference is the person who's just bored, because at the moment there's not a lot of stimulating things happening in their life and there's a kind of pause. They can experience pleasure and excitement when they're put, where they put themselves in an environment where they're stimulated. Whereas if you're depressed and normally you're an excited, happy, enthusiastic, engaged person, I'll put you in those situations that usually you love and they'll fall flat. You won't feel excited and you won't be able to climb out of that bored, depressed state because something has changed in your brain to make you unresponsive to it. That's the difference.

Dr. Stieg: Are we then saying that everybody that is clinically depressed needs medical management?

Dr. Friedman: No. Actually most of them will get better spontaneously.

Dr. Stieg: And how long? How long does that take?

Dr. Friedman: It can take a couple of months to get out of a depressive episode, so you wouldn't want to leave it untreated. But the natural course of depression after first episode is the majority of people will get better.

Dr. Stieg: And during that time they should undergo what?

Dr. Friedman: So the fact that the depressed brain is biologically different than the non-depressed brain doesn't mean that you need a biological treatment to get better from depression because your brain is responsive to lots of influences like talk therapy, which is very effective in treating depression. But you know, we know that that changes your brain also. So does exercise. So does travel. So the brain is very open to influence and the depressed brain is open to lots of influence. So if I get depressed people to exercise and I get them to talk about what's bothering them, they feel better. And if you actually study people who are depressed with different types of treatment, when they get better, the brain changes in surprisingly similar though not identical ways to treatment.

Dr. Stieg: Are there, functional MRI scans that have been done that demonstrate the brain is, has plasticity and can improve structurally with either talk therapy or a biologic therapy?

Dr. Friedman: Yes. So there are imaging studies showing that the changes from talk therapy and the changes from antidepressant therapy are very similar though not exactly the same. And so these are blood flow changes. So they're functional, not structural, and they converge and they look pretty similar, but they're not exactly the same, which is probably why talk therapy and antidepressants are in combination, complimentary and synergistic.

Dr. Stieg: Is meditation beneficial for a patient or a person that has a predisposition towards depression?

Dr. Friedman: Well, we know more about the benefit of meditation, I think for anxiety than for depression. Clearly it's effective for anxiety. I don't think it's actually been studied well for major depression.

Dr. Stieg: I was just thinking about it because of the known positive impact on structural changes in plasticity within the brain with meditation. I was curious whether there was any data on that. Every patient I see, they always worry about, "Am I going to pass this on to my children?" What component of is genetic? And if I'm depressed, how much do I have to worry that my children are going to be depressed?

Dr. Friedman: The heritability of depression is actually small. Most people who are depressed don't have a parent with depression. You know, I always think this is funny. When people go out and they get the 23andMe and they get all the genetic markers and they have a risk factor for disease X, Y, and Z. You know, the little secret is most of those risk factors, especially with behavior contributes so little to the overall risk that most people with those factors don't have the disease. And most people with the disease may not even have those risk factors. I would say. You know, if you're somebody with depression, the odds that your kid has depression are maybe slightly higher than the general non-depressed population, but it's not that high.

Dr. Stieg: You're a depressed patient and you've seen your psychiatrist, you've done talk therapy that hasn't helped you try the serotonin reuptake inhibitors and that hasn't helped. Is there anything new coming out that's being used to treat depression?

Dr. Friedman: Yes. So there are a new class of drugs starting with ketamine. Drugs that actually work on a new neurotransmitter in the brain that the current classes of drugs don't touch. And that's glutamate, which is a different neurotransmitter than all of the current available antidepressants target.

Dr. Stieg: So we've gotten back to the uh, glutamate re-uptake inhibitors. We found some new drugs?

Dr. Friedman: Ketamine is an old anesthetic, right? And it has very strong, very rapid antidepressant effects.

Dr. Stieg: Transcranial motor stimulation is quite interesting and it's being used in the treatment of depression. What is it and does it really work?

Dr. Friedman: Right? So transcranial magnetic stimulation involves just putting a magnetic field over the scalp with a magnet and then inducing an electrical change in circuits in the brain that are involved in mood and it doesn't involve being unconscious and you don't need anesthesia and has almost no side effects except maybe a slight headache and it is effective. It's not as effective for depression as—

Dr. Stieg: 50% of the time? 75? What, do we have any numbers?

Dr. Friedman: Most people who get it tend to have failed, you know, lots of treatments. So the response rates are lower than you would expect. Maybe 50%.

Dr. Stieg: Cause of the hardest of the hard cases?

Dr. Friedman: You're dealing with resistant patients so they may be lower. It's not as effective as the most effective treatment for depression, which is ECT or electroconvulsive therapy.

Dr. Stieg: Which is much more involved and — what are the side effects of that?

Dr. Friedman: The side effects of VCT? You know the side effects of the brief anesthesia, you get some memory loss for events right around the day you have the treatment.

Dr. Stieg: But not permanent memory.

Dr. Friedman: No, no, no, no. There's no evidence that there's permanent memory loss, in ECT.

Dr. Stieg: And and is that a really effective therapy? Or again, is it, are we talking about the hardest of the hard cases?

Dr. Friedman: It is the most effective treatment for depression.

Dr. Stieg: Do you use it early on in a therapy then or not?

Dr. Friedman: Yeah, we use ECT for people that have failed several antidepressants, so it's for refractory patients.

Dr. Stieg: Post traumatic stress disorder is also a very popular subject right now with, with the veterans coming back and it's a complex psychological disorder, but one part of it is also also involves depression in the PTSD patient. Do you treat the depression separately or do you treat the entire syndrome for the patient?

Dr. Friedman: So people that have PTSD and depression are particularly complicated to treat and hard to treat because you can't treat one without the other and they often go together so you have to treat them both and the treatment for PTSD is never just a medicine because PTSD is basically a form of fear learning that's gone awry and in order to learn not to be afraid you need therapy, you need some form of psychotherapy because you've had to learn something.

Dr. Stieg: Treatment for PTSD involves some talk therapy but also eye movement desensitization and the numbers that I was seeing for that actually astounded me, that they're effective 80% of the time. Is that true?

Dr. Friedman: There seems to be no question that EMDR works. We don't know how effective it is and whether it works in people who have more severe PTSD. And it works by moving the eyes in a certain direction while you get the patients to talk about these upsetting experiences they've had and somehow they have some change in their brain and their experience so that they don't have the same symptoms they had before.

Dr. Stieg: But it's effective.

Dr. Friedman: It's effective, how effective it is and for what forms, how severe the PTSD is. We don't actually know.

Dr. Stieg: Your therapeutic goal with post-traumatic stress disorder is what?

Dr. Friedman: The goal is to teach the person that the thing they're afraid of is no longer a danger and they should learn to be unafraid. The problem in PTSD is that somebody has learned that a previously safe situation is now dangerous. So if I were mugged on the street — I've never been afraid of being in the street, but when I develop PTSD, I'm now going to be afraid to walk out on that street because it's associated with a terrible thing that happened to me. So in treatment, you're going to take me and bring me out to the street in a safe setting and show me actually the street is no longer a danger and you have no reason to be afraid of it. And what you're going to be doing is teaching me that I have learned an association, which is now incorrect and I'm now going to feel safe on the street. But what you didn't do with this treatment is get rid of my old association. It lives in my brain alongside the new safe memory you gave me. So the problem is that exposure therapy gives new safe memories but cannot touch the old bad ones.

Dr. Stieg: How do we go about reconstructing our memories?

Dr. Friedman: Since the old bad memories are in the brain and they live aside the new ones that we've given people, the two are in competition with each other, which leaves people with PTSD always vulnerable to being retraumatized. So can you take an old bad memory and alter it? That's what you want to know. And we know there's some early evidence that you can interfere with memories and you can actually alter them. Experiments were done, let's say with people who have spider phobia — arachnophobia. And what happens is you can actually interfere with the link between the thing the person's afraid of and their emotional reaction. So they can actually be around the spiders without being phobic of them. They will still remember that they were afraid of them. So you're not getting rid of the biographical information. They know that they once were afraid, but when they see the spider, they don't have a fear response anymore. That's possible to do.

Dr. Stieg: That makes sense to me. Cause I was thinking that once a memory is in your brain, unless those neurons die, it's going to be there. So I guess it would seem to me that, you know, through plasticity, how are we reassociating these connections so that instead of being a terrible response, you can actually cope with the situation.

Dr. Friedman: Yeah. Because you probably can alter the link between emotions and the actual, you know, memories. But some trace of the actual learning is going to be there.

Dr. Stieg: That leads us into, for me, a sad subject, as we talked about depression, suicide is the worst manifestation of that. What is happening there?

Dr. Friedman: Well, what's happening that people who are depressed, severely depressed, feel hopeless and they actually don't believe they're ever going to feel better. And so they've got a distorted view of themselves in the world and they often develop suicidal feelings and thoughts. And about two to 12% of people with depression will go on to kill themselves. And considering the rate in the general population is about 12 and a hundred thousand. Having depression is a very big risk factor for suicide.

Dr. Stieg: In terms of the cause of death, you know, that's a fairly significant number. What global number do you quote when somebody says how many people die of suicide related to depression? Is it a million a year or?

Dr. Friedman: So the lifetime risk of depression, let's say, just pick 10% so now you're talking about, you know, 30 million of whom only a small number have severe depression cause severe mental illness is rare. So it's a much smaller number than that.

Dr. Stieg: My loved one says to me that she's depressed. When do I need to be alarmed about the level of her depression?

Dr. Friedman: Yeah, well if you have a loved one who's depressed, you want to get them help and you also want to know whether they're feeling or thinking about suicide. So people should not be afraid to ask that question. A lot of people are afraid that if asking the question is somehow going to encourage people to do something they wouldn't do. People are afraid to ask or talk about suicide will somehow implant the idea. That's incorrect. We know that's wrong.

Dr. Stieg: Are there environmental factors that play into suicidal rates changing?

Dr. Friedman: So the suicide rates have been going up and down for the last 100 years. So what most people don't know is that although the rates have gone up in the last few years, they'd been much higher in the last 100 years. So the highest point was right after the Great Depression. The real problem is that the suicide rates have not dropped over time. Like every other major illness that kills people, like the rate of heart disease and stroke has gone down. Why?

Dr. Stieg: With the advent of all your drugs you haven't been able to change this? *laughs*

Dr. Friedman: Cause you know what it is? Because we threw a lot of money at these problems and we started treating them. We have statins, we have anti-hypertensives. So with depression, yeah, we have antidepressants, but it takes more than an antidepressant to get people better and keep them better. So the problem is, you know, as a public health problem, we've done almost nothing to change the rate of suicide in the United States in the last century. We need to treat people, we need to go after depression the way people declared war on cancer. Declare war on depression.

Dr. Stieg: Is there a link between if I'd manifest signs and symptoms of depression when I'm 15. Am I more likely to have a serious depression when I get to be 50 and maybe commit suicide versus, I'm 40 and I start getting depressed.

Dr. Friedman: The curious thing about depression is you can have a chronic depression that's very treatable that just hasn't actually been evaluated or treated and you get better within weeks and also so chronicity and difficulty in treating or getting better or not related. Or you could have an acute depression, which is super hard to treat. So the amount of time that somebody has been ill isn't actually a good predictor of whether they're going to get better. There are other factors of the depression.

Dr. Stieg: Are there forms of depression? I mean we as doctors like to come up with classifications for everything. Number one, are there forms. And number two, are there particular forms that are worrisome to you as a psychiatrist for leading to suicide?

Dr. Friedman: Yes. The most serious form of depression is what we call delusional depression or psychotic depression where somebody doesn't just feel depressed and feel worthless and hopeless, but they develop delusions and they have thoughts that say, people are going to kill them or they're going to die of malnutrition, or they have delusions of poverty. That could be a very wealthy person and basically say, my life is over because I've lost all my money. And you look at their bank account and you say, what are you talking about? You still have a job. They have an idea which is false and not responsive to reality testing. That's a very severe form of depression which is associated with a high risk of suicide.

Dr. Stieg: Are there new drugs coming that will help us treat depression and hopefully diminish the suicide rate?

Dr. Friedman: Yes. There are a group of new drugs that target a new system of the brain, the glutamate transmitter in the brain that have an advantage in that they work faster than the older drugs. And they have specific anti-suicide effects, which is distinct and interesting.

Dr. Stieg: And this would be, we could use this across all populations, children, adults.

Dr. Friedman: Well we don't know yet, aside from adults with failed antidepressants cause those are the ones who are now getting it and being studied. So we don't know yet whether kids will respond or adolescents with depression will respond.

Dr. Stieg: As a psychiatrist, I, I'm sure that depression is one of the major things that you have to cope and deal with on a daily basis. What is the key message that you want to get out to people about number one, recognizing it and number two, helping somebody that has it.

Dr. Friedman: So I think the most important thing to realize if you've got depression is you're in good company. It's extremely common. It's also very treatable that if you're depressed, even if you believe that things aren't going to change and you're not going to get better, you're wrong.

Dr. Stieg: You've got a treatable illness, and the trick is to get them to understand and believe that, right? Yeah. Yeah. You just beat them over the head. Dr. Richard Friedman, thank you so much for spending this time talking with me about both suicide and depression, and I hope that we've provided some insight into the treatment of these diseases.

Dr. Friedman: It's my pleasure.

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When Demetri Kofinas was diagnosed with a benign pituitary tumor, he faced bizarre symptoms and difficult choices. With the help of his father and Dr. Jeffrey Greenfield, Demetri took on the challenges and came to a decision. 

Dr. Stieg: I'd like to welcome my two most fascinating guests today, Demitri Kofinas, and Dr. Jeffrey Greenfield. Dimitri is creator and producer of Hidden Faces, a podcast exploring the underlying forces driving global change. And Dr. Jeffrey Greenfield is a Professor of Neurological Surgery specializing in minimally invasive approaches and the complex treatment of brain tumors. I wanted to first clarify for us what the difference is between talking about a benign tumor versus a malignant tumor and then we'll get into where they cross over into the gray area. But Jeff, would you mind talking a little bit about what the difference is there?

Dr. Greenfield: I think that's a really great place to start because that really is one of the more confusing features of being diagnosed with a brain tumor and families will often jump right to the question as to whether or not the tumor is malignant or benign. The really interesting part about craniopharyngioma is that it is a benign tumor, but it carries with it so many complicated features that are often associated with more complex and even sometimes malignant brain tumors with respect to how it affects the brain. It's a little simplistic to call it a benign tumor because while the pathology, what we see under a microscope may be benign. The consequences to the brain and the person experiencing both the effects of the tumor itself and the repercussions of surgery are anything but benign.

Dr. Stieg: And Demitri, I think you can give the personal aspect here. You I'm sure were told though, this is a benign tumor — it's about a decade ago now when you were diagnosed. It had profound impact on you, your life, and who you really were at that time.

Dr. Greenfield: I had gone to a surgeon at another hospital and I had a very negative experience with what he told me. If I remember correctly, was two, I spoke to one over the phone, which was out of New York, and they said, you got get to the surgery now. This is going to grow a hundred, you know, they didn't say a hundred percent I forget what they said, but it was like, it's going to grow. You better do it now rather than later. And another one from New York told me, whatever this tumor is going to do to you, it's not going to be as bad as what I'm going to do to you. And he had a tool on his desk, and they only do craniotomies there from what I understand. And he had a tool on his desk, it was a big tool and he said, you see this like, you know, go in your head, and — I'm kind of paraphrasing here, but that that really kind of was the experience.

Dr. Stieg: So they frightened you.

Demitri Kofinas: It was super scary. My father was with me then and he was my advocate and he was walking me through this process and he was devastated by the situation.

Dr. Stieg: He was with you at the doctor appointments?

Demitri Kofinas: He was.

Dr. Stieg: Was he devastated by the way the doctors were relating to you or by the information you were getting?

Demitri Kofinas: He was devastated by in that first instance, my dad, I think, on some level my dad was relieved because he wanted to believe that he could, we could. That it would be okay that it wouldn't grow because the doctor basically said, it's probably not going to grow. It's been there since you were born. I would leave it. But then he said to me, uh, this is, I'll never forget this. He said, "But don't come back to me in a wheelchair with blinders on and blame me, or something like that." It's totally nuts.

Dr. Stieg: The amazing part about this is early on in your process, you're normal. Now. You find out that you've got this quote benign tumor and it's two physicians you've met with have scared you to death. You and your dad are now having to cope with this.

Demitri Kofinas: I became very depressed. I mean it was interesting. My first reaction was there was almost a kind of you, not euphoria, but you know when you suffer, you go through a lot of suffering. There are periods where you just feel, it's almost like there's a transcendent feeling to it. I just remembered losing my inhibitions. Maybe that's the best way to put it. I lost all inhibitions in a radical sort of way. And that ended up actually then coming back in a much more, uh, in a much more constructive manner later, which was, I would say, the biggest contributor to my life changing around in a positive way. It was devastating. I became depressed. I had a great job working in strategic product development for Cablevision, just me and a handful of people picked by the lead engineer for the company. And I quit. After a few months, I was so depressed. I didn't like what I was doing, why I wanted my life to mean something. I was afraid that I was going to die. I didn't know how long I was going to have and I, I felt like I wasn't living my life, but I didn't know what I wanted to do and I was depressed and I just wanted to, I just wanted it to be over somehow. I didn't want it. It was just terrifying. It was hard. It was. And then, um, eventually I was able to turn my life around, you know. I fell in love. All these things happened for me and I had let it go. I'd forgotten about the tumor. And then, uh, at some point the symptoms appeared.

Demitri Kofinas: I was beginning to play Tetris incessantly in the summer of 2012, which was super weird because I could tell you we've all probably played Tetris. But it wasn't until this experience that I realized what a dumb game it is. It doesn't require much of any intelligence at all.

Dr. Stieg: Glad I've never played it.

Demitri Kofinas: It doesn't, I wouldn't have known to tell you that if I hadn't had gone through this experience, but it was this, it was a, a sort of, I don't know what people do when they have tumors. I'm sure Dr. Greenfield's seen all sorts of crazy things. But I — then I was also smoking incessantly, by the way, in which I was embarrassed about, when I met with Dr. Greenfield and I had to get a chest scan. And afterwards he, I think he even told me explicitly that he better not catch me smoking. And I, I remember feeling super anxious or guilty that I might, you know, be confronted by Dr. Greenfield in a random place. But anyway, to, to bring it back. I was playing Tetris incessantly during production meetings. I was, the host of my show was asking me questions. I was playing Tetris. So that was weird. And I began to smoke incessantly. That was weird too. But, it wasn't until my drive up, we got the U-Haul with my ex-girlfriend from Washington DC, and drove up to New York. And I found out that my grandfather had died. And I did not remember that fact until about a month or two after my surgery. Most of my memories came back, what felt, what felt like days after my surgery. But they were these sort of things that came back later. And that just came back one night and I emailed my sister and I said, I just remembered that our grandfather died and I expressed a bunch of feelings about it.

Dr. Stieg: Perhaps Jeff, you could give us a little bit of groundwork here about why, where this tumor is Demitri would have had these problems with memory, emotional changes, concentration changes and things like that.

Dr. Greenfield: Well, I don't think Demitri and I talked too much about whether or not that was going to get better or not. I think that when I usually talk to patients and their families, like I was talking with you and your dad. We're really so much more focused on the things that we're familiar with that are tangible things like the pituitary gland and the hormones that it creates and the impact that the tumor might have on your vision and the repercussions of surgery. And I think we often forget about some of these cognitive impacts that tumors might have. The neuropsychological aspects of craniopharyngioma are hard to understand. And what scientists have looked at and explored for this is it's pretty minute. And so we're really on the tip of the iceberg in terms of understanding why this all happened to you.

Dr. Stieg: The decision process that you were making was when you were normal except for this questionable testosterone level. Over time, you started having symptoms both memory wise but also emotional. But the other large part, it seemed to me about your decision process was you were terrified about losing pituitary function and the thought of being on all those replacement hormones. And maybe you can talk about your emotional part and Dr. Greenfield can talk to us a little bit about what that means for a patient.

Demitri Kofinas: This whole experience was devastating for me. Dr Greenfield mentioned the possibility of blindness that was a risk, a major risk of surgery. The only options that had been presented to me were full craniotomy.

Dr. Stieg: Craniotomy meaning making a big hole in the skull.

Demitri Kofinas: Making a hole in my head, yeah. And using that tool, that medieval device that the other physician was waving at me — or the endonasal surgery or transsphenoidal. But these were just medieval. This is just what, you know, what is this thing? And in all of those cases, that was a risk as I understood it, of blindness. So I was stuck with those images in my head. And I think also to be honest, it wasn't just that I had a hard time remembering what Dr. Greenfield had told me because I remembered it in a way, but I biased the other ones. I was so despondent and I was so afraid of opening my heart to the possibility that something good could come of this situation that I, I was unable to really hear what he was saying, which was we can do the surgery with no side effects.

Dr. Stieg: Loss of vision is pretty understandable, but this tumor also involves the pituitary gland. Jeff, perhaps you could explain if you lose that gland, what does that mean for a patient?

Dr. Greenfield: Pituitary gland, people often have, as kind of a rudimentary idea, that it controls hormones in a global sense. And it is true. The pituitary gland is actually made up of an elegant mix of lots of different cells. Each one which secretes a specific molecule, which then interacts with the brain in a complex feedback pathway to allow the body to do a number of things. It helps the body make steroids. It helps the body make the hormones that regulate the sex hormones, how we make our eggs and our sperm. It affects the levels of thyroid molecules in our body. So there are a complex harmony of molecules that the pituitary gland regulates. And the key for patients with craniopharyngioma like you had, is that it's not actually the pituitary gland that was dysfunctional in your circumstance. We weren't worried about making it dysfunctional. We were worried about the connection between the pituitary gland and the brain. There's a very thin little fiber bundle called the stalk that actually connects the pituitary gland to the brain. And that's where craniopharyngioma comes from. And so it's almost impossible to remove a craniopharyngioma without a significant risk of damaging that stock, thereby disrupting this kind of beautiful highway between the pituitary gland and the brain. And that's the situation that you've found yourself in trying to balance.

Dr. Stieg: And what that means for the patient, when Dr. Greenfield talks about all of these various hormones is really what the patient describes is change in sex drive, change in energy levels, change in sleep, change in the ability to concentrate, change in their ability to deal with stress or not deal with stress. The impact that you are worried that, oh my God, if I have this surgery I'm going to be left with, with the symptoms that actually eventually developed for you.

Demitri Kofinas: Hearing Dr. Greenfield, talk about the pituitary stalk. I just had visions again of how complicated the surgery appeared to me both before and afterwards. I sent Dr. Greenfield email an email the day after I got released where I, I expressed my just, awe at what he and his team had done and it just, just hearing it again, just thinking about that he was in my brain and there was just such a narrow margin for error. No margin for error.

Dr. Stieg: Another interesting component of all this is the relationship you had with your girlfriend at the time and the relationship that you had with your father. You said he's a physician. Sounds to me like he was a real guiding force and light for you in this process. How did those things change as your disease progressed?

Dr. Greenfield: Well, I didn't see my dad much when I was getting my, my symptoms. I was living in the city, I was living with my ex girlfriend and she was, you know, working a lot and I was, I was home, you know, uncharacteristically despondent, not just despondent. I would say what was uncharacteristic about my condition was that I was stumped and that's not something that is usual for me and it was so, it was so, it was so difficult for me and what was I doing? I was going out in the balcony and smoking incessantly, smoking cigarettes and throwing them on the balcony. Not tying my shoelaces. I mean I was doing all these things and I spending a lot of time alone. I lost the capacity to imagine and that impacted not just sex. I realized so much of what was missing only when it came back.

Dr. Stieg: What was it about the doctor patient relationship that you obviously had some frightening things happen early on. Then you met dr Greenfield and a light went on that this was the way to go.

Dr. Greenfield: Well, look, I grew up around doctors, so I know doctors in and out. I think it's a tall order to ask most physicians to fulfill the emotional duties that we wish they would fulfill. Uh, and that I think in some ways they should be able to fulfill. Unfortunately, they don't often, I'd like to say your physician, your doctor should express a certain, I don't know what the, what, how you would describe it as, uh, a warmth of basic sort of empathy. But I think that's a tall order to ask for honestly. You know, I don't know if there's an incompatibilities with most physicians, the type of learning and expertise that it requires to be a physician and the emotional intelligence that is also necessary. You know, the type of patch Adams, but dr Greenfield did have that. If it were not for my father, I wouldn't have found dr Greenfield, you know, none of this would have happened.

Demitri Kofinas: He worked very, very hard to make it happen. He didn't just apply his expertise and his intelligence and his vetting capacity, but his persistence and he had reached out. It started by reaching out to someone at Harvard who had directed him to someone who was at a conference in Germany who took my call with my father and said, you need to speak to this woman. And she said, you know, this is too big for radiation, at least right now, but you should speak to Greenfield. And, and my dad, that's the one thing stuck out to my dad that he said to me, and he said it repeatedly, was that she said, "He, he can, he might be able to come in from above." Which is so weird to hear given everything that we had been told. And then we met with Dr. Greenfield together. And that was basically what he said. And it was, to me it was just like, what are you talking about? Like, you know, I don't know what you're saying. Like I have a brain up there and what do you mean you're going to come in from up there and you're not going to cut anything. But my dad got it and I was in such a fragile intellectual condition that I was unable to process what he said, but I was able to Intuit from my father's emotional relief.

Dr. Stieg: Jeff, maybe you can in lay terms, describe what simplistically was different about what you were offering versus what Demitri had heard before.

Dr. Greenfield: Yeah, I was thinking that maybe we needed a pause there to explain a little bit about what he's referring to because there are a number of ways to get to the center of an egg. And essentially when you're talking about a large craniopharyngioma, this is a basically a big mass that's right in the center of the skull. And so, the ability to get at it from different orientations through the nose or through the skull, through a big hole like we mentioned before, are certainly things that are, have been passed down through generations. And it's the way that most surgeons address these. In a funny way Demitri, the fact that you waited so long and were so, um, insistent upon continuing to find other alternatives probably is the single factor that allowed us to approach it via this technique because it had gotten so large that the big kind of cystic portion, which is a fluid balloon, like a sac that comes off the tumor, had actually extended so far up into the middle of your brain that it went into an area called the ventricle. And we don't often see tumors that large in adults. And so when you look at a picture of your tumor from the side — I remember going over this with you. The actually the shortest distance to get to the tumor was actually right through your brain. It obviously involves going through your brain a very short distance, but that accessibility allowed us to access it through a very, very small hole with a very, very small instrument called an endoscope and actually drain out all the fluid and reduce the size of this big cystic mass down to a small fraction of what it was originally.

Dr. Stieg: We've gone through the lead up to surgery and we'll come back in another episode to discuss what life is like after surgery.

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Memories return – along with a surge of confusing emotions – after Demetri's surgery to remove a craniopharyngioma. Dr. Jeffrey Greenfield joins his patient and Dr. Stieg to talk about revelations after brain tumor surgery: Demetri learns the value of surrender while his neurosurgeon develops a better understanding of his role in his patients' lives.

Dr. Stieg: I'd like to welcome back Demetri Kofinas and Dr. Jeffrey Greenfield. We've been talking about craniopharyngioma and Demitri has gone through the history of his life up to the point that he had surgery and the intellectual and emotional changes that he'd had on his life and his relationships and his work, and he then had surgery with Dr.Greenfield. Now I'd like to concentrate more on what happened after. This was obviously an anguishing episode in your life that went on for what, about five years prior to having the surgery and then you had the surgery in what, 2013? What happened?

Demetri Kofinas: Well, by the time I went in and had surgery, I was, I had full blown anterograde amnesia as I think we either stated or, or it was implied by what I was saying in terms of the symptoms. I couldn't remember much. I couldn't remember who I had just seen. I couldn't tell you what a giraffe was. I could tell you it was an animal. I could tell you had a long neck, but I didn't know what an animal was. If my symptoms had persisted after the surgery, I wouldn't have probably known where I was. So the first indication that I had had some relief as a result of what happened was that I even knew where I was. And I knew immediately where I was. And I remember seeing my father and my mother and, uh, my, uh, my girlfriend and I had told my dad before the surgery and I remembered this, "I'm going to look to you and I want you to tell me what happened." And I looked at him and he said, you know, it was great. And, I remember my dad saying that he saw the hyp— that Dr. Greenfield saw the hypothalamus pulsating after the, the pressure from the cyst had been removed. And I said, "Wow, he saw, he saw the hypothalamus pulsating." I understood immediately what that meant. And so immediately understood that I, I was getting better and my father had, that was an emotional experience for him because he hadn't seen that. I mean—

Dr. Stieg: You saw that the lights were on.

Demetri Kofinas: Exactly.

Dr. Stieg: And, you appreciated that the lights were on. Internally and emotionally, how did that affect you?

Demetri Kofinas: Oh my God. I didn't have my cell phone on me and I wanted all these numbers cause there were certain people in my life who had stood by me or who I had a close relationship with during this time as I wanted to call them and tell them how, how well I was. And they were so overwhelmed, they could still tell you the story of what it was like to hear it from me. It was a, I heard from other people's voices and from their facial expressions when they saw me, it was an affirmation that I was getting better. I was okay. It was a miracle.

Dr. Stieg: So for you, it was an awakening.

Demetri Kofinas: It was, um, first of all, the reacquisition of memories that I had never remembered making, but that all of a sudden were, there was one of the scariest things that I've ever, because it was evidence of how messed up I was and there was no guarantee that that was not going to reverse.

Demetri Kofinas: So it was scary. At the same time. It was exciting. I mean, when I left the hospital and I came home, I wasn't able, for example, to use Skype for months and I thought it was because Skype was broken or my computer was broken, but I just didn't remember the password. I go home and just enter my password, my computer. I go into my parents' house put in the code for the garage. Everything just started. It was like, you know that sound on your Mac when you hear the unclick—.

Dr. Stieg: You got your life back.

Demetri Kofinas: Yeah. But literally everything unclicked.

Dr. Stieg: Jeff, what did you see? The same kind of changes?

Dr. Greenfield: Well, I mean I'm getting a little emotional because, no, I mean I think to touch back on what Demitri had said before about how do you, how do you find the right balance as a physician with the physician-patient relationship so that you emote that empathy and you create that connection and warmth but at the same time protect yourself against what we do, which is a very scary field sometimes. And I think we all as physicians find that own particular balance and that own line where we get as close as we can and feel that it's comfortable. But we don't operate on our loved ones. We don't operate on our friends. And there's a reason for that. And so I think I might not have appreciated the intensity with which you were experiencing that rebirth and that renewal. And again, I read that article afterwards and it blew me away that maybe I was blind to some of the things that you were experiencing before and actually the rebirth that you had after surgery. Clearly I knew it was successful and in a technical sense and looking at the MRI scans, I felt validated with those kind of metrics that we're familiar with. But you know, it's actually really powerful for me to hear you describe it like this.

Demetri Kofinas: It was, it was kind of like the movie Awakenings, that particular moment in my mind, the way I remember it because everything was kind of this rebirth. Everything was, and uh, and I remember it was like five in the morning, six in the morning. It was like before you did anything else. It must have been when you came to my bedside was the day that I got released and you were just sitting right across from me. And I just remember waking up and just seeing you there. It was the weirdest thing. I was like, what is this? *laughs*

Dr. Stieg: How long has he been watching? "Hope I didn't do anything embarrassing!"

Demetri Kofinas: So great. Right? Cause like for me, Dr. Greenfield was in this, in this story. I mean, I was the protagonist. Clearly, I was the one with a brain tumor. But, you know, chief, chief character, right? And so it's an unusual feeling to have to give your life to someone that you hardly know and for them to, to service you in a way that is not just, you're not just grateful for, can't even, it's not even reasonable to expect that type of outcome. And so you have an unusual feeling of gratitude that is just not normal for any other place in your life. You don't normally feel that way about someone that you don't know. And so that was, you know, those were intense feelings that I had.

Dr. Stieg: You seem to be a person that's very comfortable with expressing your thoughts and emotions. And I wanted to touch upon one of the aspects that we as neurosurgeons, unfortunately I have to deal with on a daily basis is not only your disease process, but the process effect on both you, your emotional sense of self, your relationship to your surrounding world, and also your relationship with the loved ones in your, in your life and their relationship with you. And our role as physicians trying to help you balance that. Do you have any advice for people about how to deal with all of that stuff going on? The emotional, the physical.

Demetri Kofinas: Well, it's a big question. Do I have any advice? Um, people have reached out to me over the years. Many people have reached out to me from having read my article or, or for other reasons and I have never shied away from helping people on an individual basis. Some people reach out to me and it's like, you know, you want to say to them, "Why are you reaching out to me? You should reach out to a physician. This is, this is crazy."

Dr. Stieg: That was the point I wanted to get to is, like you said, everybody is different. But do you think that recognition of whatever the situation — is probably the key component? I recognize that you feel badly about not remembering and now all of a sudden you remember. I recognize that you ignored me and just, you know, giving the person permission and talking about it.

Demetri Kofinas: Yeah. The worst feeling in the world is when you're going through hell and everyone around you is not experiencing what you're experiencing. And they have the luxury of playing it down. Yeah. And that's the worst experience for anyone to say, "Oh that's good. It's going to be okay." No, it's, you don't know it's going to be okay. You don't know that it's going to be okay at all. Don't tell me it's going to be okay. Acknowledge what I'm telling you. Acknowledge what I'm feeling. And that was an experience that I had before my surgery. And it was an experience I had after my surgery. The first time I cried was when I came home after my surgery and there was a friend and God bless her, it's not, it wasn't her. You know, she did the best she could, but she happened to be there and she, uh, she said, "It's over now. It's, it's behind you. You've got to move on." And I just remember being so angry cause I just thought, you know, I had just been through all of this. You haven't been through any of that. And, and, and in this, just, this one moment makes you feel uncomfortable. You're not doing it to hurt me. I just remember one of the experiences I had was this, the resentment and anger that this had happened to me. It's such a young age and my inability to relate with the people of my age group. I didn't know anyone else that had had a brain tumor.

Dr. Stieg: Did you get help with that?

Demetri Kofinas: Well, I was seeing a therapist after my diagnosis who I still see. He was a wonderful support during the process, but again, I would just say like, it's just one of things where you can't — also for loved ones, like I just feel like the best way to handle the situations for the people around a patient is just to be as transparent, honest, and unfiltered as possible.

Dr. Stieg: Give you the space.

Demetri Kofinas: Yeah, and I feel like, you know, people want to feel seen and they want to — I think that you feel alone because you are alone. Look at the end of life. We're all alone. You know, we have to face death on our own. And whether someone's with you, they're not going with you. You know, Christopher Hitchens, the writer and intellectual, when he was facing death, he wrote a book on mortality. He was writing out his thoughts and one of the things he said was that the worst feeling is not just that you're at this great party and someone taps you on the shoulder and says, "Got to go." But it's that the party is going to go on without you. It's the sense that you're leaving everyone. And that was what I felt when I went into surgery. I had that experience, this just an animalistic level of fear. And it was in that moment, it was a fear of loss of not just my mother, not just my father, but of the whole world and not knowing what was outside that door. And that was so scary.

Dr. Stieg: So you've had the luxury of thinking that you were leaving the party and now you're back in the party. How is, how is life different?

Demetri Kofinas: How's life different? I mean, one benefit of the experience was seeing old things anew, but in fundamentally more profound ways. There were movies that I wanted to watch. Again, I'm a very big a visual learner and so I, I've, I never realized really until after my surgery that I had a natural gift for that almost photographic memory, you know, and I can recite, you know, lines upon lines for movies and scenes, which I actually did for fun to my ex-girlfriend. I did the whole, like the first 20 minutes of When Harry Met Sally. It's so crazy—

Dr. Stieg: Hopefully not that scene in the diner?

Dr. Greenfield: Well we all know that scene, but I literally put on the movie and I was reading the lines before right before they would come and it was just crazy. But I didn't realize that until afterwards, but there were movies that stuck out to me cause I learned that way and they all made sense to me. The whole thing made sense and myths and stories. They made sense. I understood where it was all coming from. And the culmination of that was during my radiation. That was, you know, I describe it as a religious experience and I'm not religious. I'm an agnostic. I'm an instrumentalist when it comes to science. I don't have any answers, but uh, I'm a mystic in some sense. But uh, but it was, I was walking, I lived. I had a beautiful apartment at the time. I would walk from Columbus Circle all the way down to Memorial Sloan Kettering at 7 in the morning for my radiations. I was so scared the night before, you know, my mom said, "Don't worry, you know, it's going to be over in six weeks."

Demetri Kofinas: It was daily, six weeks. She's like, "Don't worry, you won't even remember it. It'll fly by." I was like, don't you get it? I was like, I don't want time to fly by. Like time had become so slow and it becomes something that I wanted. I wanted every moment. I wanted to soak everything out of life and to think that I had to find a way to get through six weeks of this, what seemed like just horrible going back to the hospital. But it turned out to be the most beautiful experience of my life. And that's not a joke.

Dr. Stieg: Well, it's clear that you've got much to share and much to teach. Jeff, what did you learn from all of this as a physician?

Dr. Greenfield: I feel like I've learned a lot throughout the entire process. I mean, I think part of reflecting on a complicated case and developing a relationship with a patient is, is fairly unique and I think we all have experiences as physicians, particularly with the neurosurgery where we can affect such a dramatic change in someone's life that the relationship changes forever. And that is both a blessing and can be a curse as well for neurosurgeons. And so for me, both reading your article and then reconnecting with you and hearing your experiences makes me very introspective about how I talk to my patients, how I will think about patients going forward with respect to the things that are not on the MRI scan. How will you reflect on the relationships that people have with their family? I feel like I do this inherently to some degree, but I think in a more conscious sense, and maybe part of my role as an educator will be to impart this to future generations, is that this is really part of who we are as healers and as doctors. It goes beyond neurosurgery or fancy technical achievements. It really comes down to why we get into the field and why we love being physicians. So I think you've probably taught me a whole lot more than the other way around.

Dr. Stieg: I really want to thank both of you for your sincerity and your honesty and what I hope this has highlighted, for certainly has for me and everybody else participating in this podcast, is an enlightenment about the complexity of the brain. Not only structurally. no, you had a tumor sitting and pushing on a certain part, but also the functional component and really — your reachievement of brain health, how you've gotten back to a healthy, normal life, and it's a, it's a physiologic, a biologic process, but it's also an emotional and a conscious development that has gone on in your life. I think that it's marvelous that you are willing to and extremely capable of sharing that set of concepts and emotions with our listeners.

Demetri Kofinas: I'm extremely lucky. I not only my lucky that I was able to find Dr. Greenfield, but I was lucky that my, as he said, my tumor had grown so much that it was protruding through the third ventricle and that the surgery was possible. I feel, I just feel grateful. I feel lucky being here.

Dr. Stieg: Do you feel like you're just lucky or do you feel like there's a sense of grace that's been granted to your life?

Demetri Kofinas: The best way I could describe what I experienced to answer your question was it felt like revelation. It felt like my life had meaning. It had, it mattered. That I mattered. That it wasn't something that I just had to convince myself of. It just was, and it helped make something that could have been so difficult. So not just easy, but as I said before, one of the most beautiful experiences of my life.

Dr. Stieg: It's interesting how people that go through near-death experiences actually have the same experience as a death experience in terms of the Kübler-Ross concept. And that's what you've been describing. Your original response to the information was anger, then you started to negotiate and eventually you came to terms with what has happened. And now because of what has happened, you've actually gotten a new lease. And it's interesting to watch how that's affected you.

Demetri Kofinas: I knew that every day mattered. And I was present in a way that I had never been before. And I was just so aware of people's emotional states and, and I was in such a place of just acceptance. And, and you know, one of the things that I learned through this process, you know, I was a fighter since I was a kid, literally and metaphorically, I never accepted an outcome that I was not happy with. I found a way, even if I couldn't get what I wanted, I fought in the, in the face of it.

Dr. Stieg: You were one of the 300 Spartans.

Demetri Kofinas: I kind of, I actually had the opposite experience after my surgery. I realized there is a time for surrender and surrender is not the same thing as quitting or giving up, and I learned the value of surrender and that has served me well in my life.

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Dr. Barry Kosofsky explains why children – especially girls – are at greater risk for concussion, and why kids under 14 should never play tackle football and certain other contact sports. Learn how to recognize the signs of concussion, when to go to the ER, and why kids with ADHD or anxiety tend to do worse when they have concussions.

Dr. Stieg: Hello, I'm Dr. Phil Stieg and I'm here today having a conversation with my dear friend, Dr. Barry Kosofsky. Dr. Kosofsky is Professor of Pediatrics and Chief of the Division of Pediatric Neurology at NewYork-Presbyterian Hospital, Weill Cornell Medicine Center, and the director of the Horace W. Goldsmith Foundation Laboratory of Molecular and Developmental Neuroscience. Barry, thanks so much for joining me. The reason I have Dr. Kosofsky here, and forgive me, I'm going to refer to him as Barry from now on, is that he is one of the world's experts on the management of concussion. Tell us what is a concussion, both what happens to the brain and what do you see?

Dr. Kosofsky: So a concussion is loosely defined as a blow to the head. That in some way alters behavior that's so vague that it makes it difficult to say who does and does not have a concussion. What we like to say is mild traumatic brain injury. By mild traumatic brain injury. We mean somebody who's taken a blow to the head and it's going to cause ongoing symptoms and those symptoms can be in a number of domains. The one we usually think about is headache and somebody who has inducible headache, meaning when they're physically or mentally active and they induce a headache, they had a concussion, they don't need a CT scan, they don't need an MRI, they have a diagnosis. If you're symptomatic following a blow to the head, you had a concussion.

Dr. Stieg: Moms and dads are worried about their kids. Can you put it in sort of a picture for them? Is there something that happens to the brain cells? Do they get rattled? You know, we don't have to get real molecular about this, but what goes on?

Dr. Kosofsky: When the brain gets injured, different chemicals leak out of the brain and that leads to some altered symptoms and immediately what we think about is confusion, nausea, vomiting and lethargy. So if your kid gets hit on the sideline or falls down at home, and that's another interesting point. The age really defines how the hit happens. Less than five year olds. Most of the concussions are just by falling five to 15 it's often sports and also horsing around and then over 15 a lot of it's assault and motor vehicle accidents as well as sports. You're looking for nausea, vomiting and sleepiness.

Dr. Stieg: If you see those things, what should mom and dad or a friend do with their patient? Where should they go?

Dr. Kosofsky: I think the pendulum has swung where now everybody goes to the emergency room, especially if their kids are under the age of five, which is conservative because they can't really tell you what they're experiencing. But what we like to say is if you know your child or if your coach knows the athlete, are they different than they were before the hit? And the key is knowing, you know, what is their behavior like? How spontaneous are they? How outgoing are they? You can look at somebody's eyes and if the elevator's not going to the top, you get concerned. So the physical signs for a parent is that my child just doesn't look right, isn't acting right. For the clinician, what we say is if they're endorsing dizziness, nausea, vomiting, or sleepiness, we want them to come to the emergency room.

Dr. Stieg: So what about the imaging stuff? Do you think everybody should get a CT scan or an MRI scan? Is it important or not?

Dr. Kosofsky: Absolutely unimportant. And here's why. The reason we say nausea, vomiting and sleepiness, it is important to bring the child to the emergency room is those are the signs and symptoms of blood in the brain. And then we need your team, the neurosurgeons to intervene. However, in the absence of nausea, repeated vomiting or any kind of sleepiness, it's really unlikely that there's anything in the head that warrants a neurosurgeon to intervene. We suggest not doing a CT scan, especially in the little ones where the risk of radiation then feeds forward to an increased risk of cancer. If you make it 24 hours, you never need a CT scan after that and you never need an MRI after that. And the reason is MRIs will not tell me anything I need to know to help treat you and you and I never do tests that have no therapeutic implication. Everybody wants to know I need an MRI, I need to know if I had a concussion. If you're symptomatic, you had a concussion and there's no reason to get the MRI.

Dr. Stieg: So now my son or daughter just had what I think is a concussion. They come back, or I see at the sporting event that they've got a little bit of a headache. They're a little bit nauseated. Should I put a pair of sunglasses on him, put them in a dark room. Since you say I don't need a CT scan, I don't waste time sitting in an emergency department for eight hours, what should I expect or what should I do?

Dr. Kosofsky: I think calling, for children, the pediatrician is the first line of defense and letting the pediatrician know and they usually want to see the child cause they know the child well. They can do a crude neurologic exam. The key is, in those first 72 hours, you do want to power down, but the field has gotten away from cocooning. It turns out if you leave kids in their rooms, they dwell on their symptoms and they're more symptomatic, not less. We're getting to a—

Dr. Stieg: So by cocooning you mean putting them in a dark room and isolating them from the family? Correct. Don't do it.

Dr. Kosofsky: Don't do that after three days. So the first three days, yes. Power down, minimize screens, minimize texting, minimize stimulation and I can't always predict what it's going to be. Some patients, it sounds, sometimes it's light, going up and down stairs, but whatever the triggers are, try to avoid them. However, starting on day three to four, start gradually escalating activities as tolerated and with kids I say go to school for the afternoon only see if you tolerate class. Usually it's copying from the whiteboard or concentrating that induces the headache. If it does, you go to the nurse's office and you don't power through it. If you tolerate it, then you spend the full day in class. Always return to school before return to play. For me, the priority is two weeks of full academics without inducing any headaches. Then you can gradually return to play cardio drills, scrimmage, game. If you experience any headaches induced along that pathway towards escalation, like with the academics you back off. So I would say as a parent, be cautious, but encourage your child to gradually increase their activities, monitoring for triggers and avoiding the triggers as best they can.

Dr. Stieg: Tell us a little bit about how children react differently to a concussion than adults.

Dr. Kosofsky: So one of the points I just mentioned is that kids, 30% of kids will not get better after concussion and 20% of adults. It's the only injury that I know of where kids take longer to heal than adults. We always the orthopedists, always joke: You have a kid with a broken bone, you put the two bones in the same room, they heal. What is it about the developing brain that makes children more vulnerable to ongoing symptoms? There's a lot of theories and no fact. One of the ideas is that the neck muscles are weaker in children and their heads are a bigger part of their volume, their body volume. So we call kids bobbleheads right? Cause the head's big.

Dr. Stieg: That's what you always called me.

Dr. Kosofsky: No, that's what's uh — the Met guy on the back of your car. So bobbleheads have big heads, weak necks, and they're at greater risk. So if you think about the same impact will confer more energy and injury to the brain in a child with a big head and a weak neck than it would in an adult. In a related story, after age 14, girls are at greater risk for symptoms than boys. And it may be that their strap muscles in their neck never develop as fully as in men. Now that's an idea that's being tested actually to see whether you can strengthen the neck muscles and it could be protective. But the American Academy of Pediatrics has come out with a recommendation, no tackle football before the age of 14. No heading the ball in soccer before the age of 14 because 14 is the time when most children have gone through puberty and their necks are a little bit stronger. That's one of the foundations for that recommendation I should mention in soccer, it's not the heading of the ball. It's going up for the header and head to head and head to ground injury. That's what's the problem and that's more evident in women than men after puberty.

Dr. Stieg: Thinking about moms and dads watching their kids play the sport then trying to be protective of their child. You've been speaking about the mechanism of injury. What should they watch for differently in a girl than they might watch for on a boy?

Dr. Kosofsky: I don't know that the mechanism of injury is different. Clearly the worst sport is boxing and the second worst sport is football. As was said in the movie Concussion, the brain was not built for football. When you then go away from these helmet sports, which hockey is one of, you get into collision sports like basketball and soccer, they are lower risk, but that's where women compete. Interestingly, if you follow those players, they accrue structural brain injury over time because there's rapid acceleration, deceleration, and this injury — we used to think it's the—

Dr. Stieg: By rapid acceleration, deceleration, you mean the head basically whip lashing?

Dr. Kosofsky: That's correct. And so that gets back to the weak neck, the head whiplashing, and then what happens is it's not the direct injury of the brain against the skull, but I think about the skull, not to get technical Phil, it's like broccoli, there's a flower and a stalk, and with rapid acceleration deceleration, the flower moves on the stock and those fibers right where the flower meets the stalk gets stretched and those are the ones that mediate balance, they mediate eye movement. And we think that's really the deep injury, the shearing of the white matter, and that's why it's so elusive on brain imaging that it's not a cortical injury with blood. That's important in the first hours as we mentioned, but it's this deeper injury that's very hard to visualize. Now, advanced MRI methods are starting to pick up on that. They're saying maybe we can use this as a biomarker of injury, but it's only in advanced research settings. It's not your common MRIs that can detect this injury.

Dr. Stieg: Let's talk a little bit about the concept of prevention. So what do you tell moms and dads or for that matter, any teenager that's starting to take up football, how do you make sure you can try to maximize avoiding having a concussion?

Dr. Kosofsky: So this is the key. We know sports are very good. Team sports build character, discipline, and we want our kids to be as active as possible. We can make it safer. So I think sports can be proactive at changing rules and making it, you see the NFL has changed the rules with quarterbacks and what kind of hits you're allowed and no chop blocks and no blocks to the head and you're not allowed to hit the quarterback in the head at all. So I think we're getting better. One of the interesting points though is helmets give the football player the false sense of security. They can lead with their head. And in the counterintuitive way, it increased the risk of concussion, not decreased. In Australian rules football. There's fewer concussions. They don't wear their helmets, so they don't lead with their heads. However, when they get a concussion, it's worse because they're not wearing a helmet.

Dr. Stieg: Well, that was also shown in downhill skiing, as you recall, that people with helmets took greater risk going down and they had more head injuries.

Dr. Kosofsky: So I think it is dangerous. We talk about, should a soccer player wear headbands? The answer is it doesn't protect your head, but it reminds you that you're at risk. It's like wearing a knee brace when you ski, it doesn't protect you, but it reminds you you're at risk for injury

Dr. Stieg: With the increase in children participating in sports and the broad diversity of sports... I mean, you've talked a lot about hockey, football, soccer and basketball, but let's face it, there's field hockey, there's horseback riding, skateboarding, bicycling, all of the, this massive number of sports.

Dr. Kosofsky: It's interesting. The Department of Defense partnered with the National Collegiate Athletic Association, so the NCAA, they now have the Grand Alliance and they're looking at 20,000 athletes at colleges across the country. If you enroll all your varsity athletes, male and female for every sport and they're trying to figure out what is the risk for each of these different sports. It turns out wrestling came up much higher than we would have predicted. Women's lacrosse and field hockey came up much higher than we would have predicted, so there are some surprises there. There are, I think, recommendations that we want to make based on that data, that a wait until you're older to play some of those sports, the collision sports and the helmet sports in particular and be looking at your body type. Some people aren't built for football. If you have a thin neck, it may not be the right sport for you. Certain bodies aren't made for ballet, certain bodies aren't made for swimming. So I think we want to be smart about picking the right sport and encouraging your child.

Dr. Stieg: I just want to say good luck to that with telling your child to pick their sport.

Dr. Stieg: Recently there's been a lot of conversation about preexisting issues and the effect that that has on your recovery from a concussion and by preexisting issues or conditions. I'm talking about anxiety, ADHD, sleep disorders, concentration disorders, mood disorders. What's the latest on that?

Dr. Kosofsky: Absolutely. A hundred percent true. Guidelines were just released about pediatric concussion and they emphasize not only importance of identifying such premorbid factors, meaning pre concussion factors, but focusing treatment on those factors. Anxiety in my clinic, so I run a pediatric concussion clinic here at Cornell, the single biggest factor predicting prolonged symptoms is if somebody was anxious before the concussion to the point where I have a cognitive behavioral therapist in my clinic.

Dr. Stieg: That's a mouthful. What is a cognitive behavioral therapist?

Dr. Kosofsky: So CBT—

Dr. Stieg: A psychologist, right?

Dr. Kosofsky: It's a psychologist who specializes in changing cognitions, by which I mean, if you're anxious and you get a concussion, when you experience this pain, I alluded to that you're physically or mentally active and you feel headache. The pain controls you instead of you controlling the pain and it spirals out of control and these are the kids that are home for three, six months or out of work or the adults out of work for a year or two. You've got to prevent that cycle from developing and to do that, if I get the history, I bring psychologists into the room, they talk about anxiety and they say, "Look, when you feel that pain coming on, deep breathing, relaxation, diaphragmatic breathing 

imagery, you're in control," and it's a game changer.

Dr. Stieg: Be good if we could teach a lot of adults to do that on a regular basis.

Dr. Kosofsky: And it's a generalizable skill, Phil. Meaning that you learn it now, but you can use it when other stresses occur. So this kind of approach will refer back out to the community. You have a smart kid, seven, eight lessons. They master it. It's a lifetime skill, but we're seeing anxiety as the biggest factor predictive of ongoing symptoms, attention deficit disorder, learning disability, also the case. And then the tricky part there is if they're on stimulants, I want them off of stimulants when they're recovering. But then they're having a harder time in school and harder time concentrating.

Dr. Stieg: There's been a fair amount of literature coming out now about concussion and then suicide risk. I certainly don't want parents being terrified that, "Oh my God, my child had has one concussion and I've gotta be worried about this too." What's the latest on that?

Dr. Kosofsky: So this relates to what do you bring to the concussion. As you mentioned, you know, some of it is premorbid anxiety and other psychiatric disorders, those predisposed for prolonged symptoms. What we're learning now, and this sort of gets to the issue of CTE, chronic traumatic encephalopathy. There's been a lot of hype about football players like Junior Seau who was highlighted in the movie concussion killing themselves and before they committed suicide, they were aggressive, they were moody, they were irrational and aggressive. That describes a lot of football players before the concussion. So that's part of the problem. These are aggressive men who get paid to be physical. However, it did turn out that there is something, a new disease that was initially described in boxers — dementia pugilistica that was then evident in football players. Some subset of whom were violent and committed suicide. That is a vanishingly small number of football players.

Dr. Kosofsky: Most people who've played football have done very well and we're trying to figure out what are those factors that are different? One of the factors, interestingly, is when you started playing football, back to our initial discussion. They looked at pro football players and who had neurodegenerative changes, so not as far as suicide, but who had Parkinson's, who had Alzheimer's, who had memory problems. If they were pros and started before they were 14 it was an increased risk as opposed to after 14 so presumably they got their heads bashed in equally in the pros, but the early exposure before 14 before that neck gets strong — that puts them at a lifetime risk for dementia. A very small risk. Very few of the football players developed it, but more who played starting before age 14 than after.

Dr. Stieg: So the take-home message for this topic, the suicide and this chronic traumatic encephalopathy, again, is the frequency with which the child as a blow to their head and has a concussive episode. Mom and dad with one concussion shouldn't be worried about the fact that they've left their kid do something terrible and they're going to be disabled later on in life.

Dr. Kosofsky: Absolutely. Um, and likewise, a lot of these injuries, I'll take kids, I give them the three strike rule after three strikes. I really don't want you playing helmet sports and I'd like you to avoid concussion sports, but sometimes the concussions occur just at home or out socially. So you can prevent, you can't put your kid in a bubble. You can try to minimize risk and get them to make good decisions. But no — three concussions is not going to lead to chronic traumatic encephalopathy. The football players in particular, the alignment of getting sub-concussive blows every play and some of the forces on the backs, running backs, the defensive backs, the linebackers are enormous. So I think that's a whole different mechanism of brain injury. There's a whole different neuropathology and we're learning there's a genetics to it. And you can't change your genetics, but it turns out the same gene APOE e4 that predisposes you to dementia and Alzheimer's predisposes you to more prolonged symptoms after traumatic brain injury.

Dr. Stieg: Over this brief time, we've really reviewed the concept of prevention, treatment, and diagnosis and recovery. What are the three or four take home key points that the listeners should know?

Dr. Kosofsky: If there's a blow to the head, no need to go to the emergency room, do let your internist or your pediatrician know. No need to go to the emergency room unless you've got nausea, vomiting, and sleepiness. If you don't and your symptoms are manageable at home, power down for three days and then gradually increase your activities. If you have inducible headaches, be respectful of those triggers.

Dr. Stieg: What do you mean, inducible?

Dr. Kosofsky: By physical or mental activity. So for kids, if they go to school and they induce headaches, if for adults, if they're at work and they induce headaches. For athletes, if they work out and induce headaches, I always recommend return, unless you're a professional athlete, return to school, return to learn before return to play. That's the priority. And then try to get as much rest and be respectful of the headache and not power through the headache and the whole syndrome will get resolved faster.

Dr. Stieg: And the longterm prognosis for this is excellent, correct?

Dr. Kosofsky: Excellent. 80% of the adults, 70% within two weeks, and I'd say 90% will get better. Long term, it's that 10% we're trying to pick up early and get them the appropriate therapy. Anxiety is the gorilla in the room. If your child is anxious, you've got to get on top of that quickly. Or if you have personal anxiety. And the problem is anxiety is rampant in our society and it's contagious. So what you've got to do is think about these psychologic approaches, these nonpharmacologic interventions: relaxing, yoga, meditating. I tell my patients to swim. Swimming is great because there's not a contact sport. It's individual to have neck problems. I should mention one last point. Sometimes the neck can be injured and it's often overlooked. So if there's neck pain, physical therapist. If you're having trouble visual tracking, visual therapist. If you having trouble with your balance, vestibular therapist. But the key to this is if you're anxious going to the psychologist for cognitive behavioral therapy, triaging patients at risk for ongoing symptoms, the appropriate treatment will take care of the other 10% that don't get better on their own.

Dr. Stieg: Dr. Barry Kosofsky, thank you for this most scintillating conversation and your analysis of the management of concussion or a mild traumatic brain injury.

Dr. Kosofsky: Thank you, Phil. I appreciate the opportunity.

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A tremor had plagued Alexandra Lebenthal since childhood. Today her hand is steady and she can finally hold a glass with ease, thanks to Dr. Michael Kaplitt and a life-changing new procedure called MR-guided focused ultrasound.

Dr. Stieg: I'd like to introduce a dear friend of mine, Alexandra Lebenthal. Alex is a leader in the financial services industry who managed and sold the successful companies, started by her grandparents and led by her father. Alex, perhaps you could tell our listeners a little bit about your experience with essential tremor and how the symptoms affected your life.

Alexandra Lebenthal: Essential tremor was something that truly governed my life for really ever since I was a very, very small child, three years old, so it was constantly a part of my trying to function and being mortified about being found out or noticed. It affected my ability to drink, pour, thread a needle, right? I mean just about any activity that you can imagine. So it truly was something that on a daily basis was a problem in terms of my functioning.

Dr. Stieg: And probably an issue when you're a teenager growing up worrying about what people are thinking and saying.

Alexandra Lebenthal: Definitely. Once in a while somebody would say, why are you so nervous? Actually got stopped by a cop once who said, why are you so nervous? I didn't feel like going into into essential tremor, but definitely — even younger than a teenager, I remember I must've been about 10 years old, just weeping to my mother about it and there wasn't, I don't even know if they had a name for it then, but there certainly wasn't anything that really could be done about it.

Dr. Stieg: Given the duration that you have this problem, had you tried other forms of therapy?

Alexandra Lebenthal: I tried three different medications. The first was propranolol, which lowered my blood pressure and I have low blood pressure to begin with. So I remember basically being passed out on the floor, not functioning. And I thought it was great. I'm not shaking, but I'm not moving either. And then I was on Primidone and Trokendi, and you know, I took them sort of out of a sense of duty, but they really didn't do anything. So I considered very briefly, deep brain stimulation and my family and friends thought it was probably a little bit too extreme. So when targeted ultrasound came along, I really jumped at it.

Dr. Stieg: I have to say that I was always pushing Alex to be thinking about this, but here to tell us a bit more about essential tremor is Dr. Michael Kaplitt, a neurosurgeon and Director of the Movement Disorder Service at the Weill Cornell Medicine Brain and Spine Center. Mike Alex was your first patient in New York after the FDA approval last year. How did you decide she was a good candidate for this procedure and what steps did you take to assess her essential tremor specifically?

Dr. Kaplitt: Right. Well, she obviously was in good general health, which was a real positive, and we were convinced that she truly had essential tremor. So we want to make sure that it really is essential tremor, not something else. And that was very clear from her exam and her history, and her family history of having family members with this. So once we were convinced that she truly had essential tremor, that she truly was not, did not have reasonable medical alternatives, and that she was in good shape, we felt that she was a good candidate for a targeted surgical intervention. Specifically with the ultrasound. I think number one, it was something that she found very attractive because we were not going to be going actually into the brain itself and we wouldn't be leaving a device behind in her body. And then the only other thing that we needed to make sure of was that her skull was favorable for this procedure.

Dr. Kaplitt: The one thing that we have to do for this procedure is we have to do a CT scan on patients, even if they seem to be good candidates because roughly five to 10% of people have skulls that are actually a little too soft for this procedure. And will absorb all the ultrasound, like when you scream into a pillow and the sound doesn't go through, so it can make it difficult to get it in for the brain. It's a very small minority of patients, but we've seen a couple in the last year that are not favorable for this procedure because of their CT scan and they've actually gone on to have successful deep brain stimulation.

Dr. Stieg: Well, I always knew that Alex was never too soft.

Alexandra Lebenthal: I have a thick skull! That's just put that as it is.

Dr. Stieg: So for our listeners, Alex, can you tell them what it was like going through the procedure?

Alexandra Lebenthal: Yes, so I will say the thing that probably took my attention away from the procedure itself was the fact, and this is for a woman, it's a big deal that you have to have your head shaved. Um, and coming from someone who had long brown hair down to my back, this was obviously a big deal. So that was probably one of the more traumatic moments of it. But I will say I was so excited to be doing this thing that was going to change my life, that I wasn't as scared as you might think I was. And what happens is, as Dr. Kaplitt knows, they shave your head, they put this metal frame on your head to keep your head still, which is also a little bit traumatic, but then you're in the CT scan and there's all these people around and people from the company that developed the technology and my husband was there that I truly felt like I was part of this exciting community that was a part of making this incredible change in my life that would ultimately change other people's lives.

Alexandra Lebenthal: I will say, and I don't even remember, Dr. Kaplitt, How long you were actually preparing for it, but I actually fell asleep, so I was kinda not, not with it until it was actually time to start the procedure. And then, that was so amazing because you start doing these drawing spirals, which anyone who has essential tremor knows is basically impossible: drawing a spiral and then drawing a straight line, which looks like a seismograph or something. And then they do the targeted ultrasound and keep bringing you out of this CT scan. Uh, the MRI, excuse me, to see how you're doing with the spirals and straight lines and just seeing it getting better and better and better until finally you're drawing a straight line. You're drawing a spiral that doesn't jab all over the place. I mean, my life changed right then and there. It was absolutely incredible.

Dr. Stieg: Having been there also, I can state that her husband probably compensated with the anxiety level standing on the outside watching it happen. Mike, what was it like for you while you're doing this the first time?

Dr. Kaplitt: Well, the first time we ever did this, I really was miraculous. It's one of those things where you know, you understand the science behind it. You understand the anatomy. I understand enough of the physics to be dangerous and so you understand intellectually about this, but actually watching without having to open to anybody's head, watching them before your eyes get better and then seeing on the screen on the MRI that you're actually taking out this very small spot in the brain without ever having opened up the head and without affecting the nearby areas really is truly remarkable. Now, like anything, unfortunately it's become a bit routine for us, but that's good for the patients, but the wonder is taken away a bit, but those first few times, it's hard to believe that this is really happening after spending decades having to open people up and actually go inside the brain to get to these areas.

Dr. Stieg: Mike, I'd like you to really describe how the focus out resound procedure works.

Dr. Kaplitt: Right? So the idea behind focused ultrasound is that ultrasound waves will actually go through the skull and they will go into the brain, but they are unfocused. They will just sort of spread out throughout the brain and on their own, each individual wave or beam of ultrasound is fairly safe. We know that women who are pregnant will have many ultrasounds throughout pregnancy, including of the developing brain, which is usually more sensitive to problems. And yet ultrasound has never been associated with any problem in developing embryos and fetuses and the children do just fine. So we know that the ultrasound as it goes through the brain is relatively safe on its own. The idea here is that we have a an array of sources of ultrasound in this helmet and the helmet comes down over the head very much like the helmet of Darth Vader that came down over the top of his bald head.

Dr. Kaplitt: We shave the whole head. We bring this helmet and we fill it up with water because ultrasound does not go through air very well. So we filled the helmet with water. So the top of the head is sitting in a water environment, just like the jelly that people use for ultrasounds of the abdomen or something else. And then these 1000 sources all will focus those beams and concentrate them on a single spot. The spot in the brain, in the middle of the circuit that regulates movement. And stability and that is the spot that's not functioning properly that we want to take out. So as these beams go through the brain, each individual beam will safely go through the brain, but together when they all concentrate and converge on that one spot, they will add up their energy. So now you will deliver an enormous amount of energy just to that one deep spot in the brain without affecting the rest of the brain.

Dr. Kaplitt: It's very much like when you were a kid, if you took a magnifying glass when it was a sunny day and try to shine the light on a leaf and you could burn a hole in the leaf because you were concentrating all of the beams of light onto one spot on the leaf and adding up the energy there to burn that leaf. It's the same concept here so that the rest of the brain is left alone. The rest of the brain is safe as these low energy beams go through, but they add up at the spot to be able to take the area out and then the patients are awake during this, because we do this very slowly, we start out with a low amount of energy that's not permanent to make sure we're in the right spot and when we know when the right spot with the low amount of energy, the tremor will start to get noticeably better and we make sure that there are no side effects, no problems with speaking or doing other things and we have them repeat the same things over and over again to make sure they're speaking okay.

Dr. Kaplitt: We have them draw spirals to make sure the tremor is okay and once we know we're in the right spot, then we increase the energy until we make it permanent and the tremor goes away.

Dr. Stieg: Alex, I'm sure that many of our listeners are wondering what it felt like when you underwent this therapy. Was there any significant pain?

Alexandra Lebenthal: There was no pain. Well, let me take that back. And it was not directly from the procedure itself, putting the helmet or the halo on — first they had to put four shots of anesthesia and that's what hurt. Nothing else hurt. The targeted ultrasound beams themselves. I compare to when you put your finger on a plug and by accident get the metal part, except you know you're not going to get electrocuted. So no it didn't. It didn't hurt at all. And nothing afterwards.

Dr. Stieg: You said earlier that you noticed immediately during the procedure that you could start drawing the swirls and so you noted the immediate change. It's been a year since you've had it done now. How has it changed your life?

Alexandra Lebenthal: So many ways and some things are seemingly innocuous to the rest of the world, but we've all walked into cocktail parties and there's the tray of seltzer and water and wine. And for me in the past, my heart would be faster. I would go through this, this mini anxiety attack of my hands going to shake and potentially knock over glasses of wine. And so just being able to walk into a party and just lift that glass of wine, pouring milk in my coffee in the morning, walking with my coffee across the room and knowing it's not going to jerk. Standing with someone and holding something and for anybody who has essential tremor, you know what it's like. It's hard to completely explain because it is so basic to who we are as people, but having that fear of somebody seeing something about you and wondering what is wrong with her and knowing that that doesn't have to happen anymore. I had a meeting the other day and somebody said, would you like a cup of coffee? I have this internal dialogue with myself about, "Yes, I would like coffee." You have no idea what it's like to actually be able to ask for a cup of coffee and know that my hand's not going to— I mean literally you have these conversations in your head and kind of chuckle at how easy it is to be normal in the most normal circumstances.

Dr. Kaplitt: I'd like to add a point, which is that first of all, for me, I think the fact that people are willing to undergo something like this is also equally miraculous. It's something that is new and hasn't been around for a while. And to be willing to accept that, I think, is an amazing thing. One of the differences between movement disorders and a lot of other diseases is that it's a very public problem. You can have a lot of diseases in your body that nobody knows about when you go out to dinner or when you do other things as, as, as terrible as it might be for you and your family and your own life. But when you have a tremor like this, it affects every facet of your interactions as a human being with other human beings. Because this is not something that you can hide. And stress makes tremor worse. So the more you stress about it, which is natural, the worse it gets. So that gives you an idea of how problematic it is for people and why they're willing to undergo something like this. And we're just thrilled to be able to offer something this revolutionary to everyone.

Dr. Stieg: I think part of the issue has been that you lived with it for so long that you actually adapted to it and I really can't overemphasize the emotional stress that that really puts on a person's life when they're dealing with what Dr. Kaplitt has said, which is something that is on public display.

Dr. Stieg: Mike, you only one side of the brain at a time which affects one side of the body. Why is that?

Dr. Kaplitt: The area of the brain that we are essentially removing with this ultrasound, or destroying 

— It's a very small spot but it's in the middle of a circuit that controls stability to some degree and there is a bit of concern that if you do the same procedure on both sides of the brain that there might be slightly higher complications and problems with speaking or with balance and stability. It's also a very high rent district, this area, so there are important things right next to it that we're trying to avoid, which is part of why this has to be done at a place that really has experience and knows what they're doing and why it takes a while because we do this slowly, so we make sure that we're only getting the spot that we're interested in, but there is also some concern that if you do creep up on some of the nearby structures of bed that it usually doesn't cause much of a problem if it's only on one side, but if you do that a bit on both sides of the brain, then the brain may not compensate for those things as well.

Dr. Kaplitt: Having said that, there is some evidence from some other types of procedures that this could potentially be done safely, particularly since we are doing this in a way where we actually can see what we're doing so we can try to tailor it in a way that would be much more precise than anything that's been done before. And so we and some other centers are getting together right now and working on a study that will hopefully allow us to treat the other side of the brain and people who are interested. Like Alex, we've already treated the first side in order to see whether this can be equally safe and effective on both sides.

Dr. Stieg: So as we know, essential tremor normally affects both sides. Alex, now you've got one hand that's not shaking and one that is, how does that affect life?

Alexandra Lebenthal: So I would do the second side in a second. I'll raise my shaky hand and my, my non shaky hand and volunteer. Certainly my quality of life is infinitely better. But there are certain things that I do notice and I will say sometimes I am slightly imbalanced, but to have both sides done would truly be an amazing thing, and perhaps I'm too brave and wanting to jump in with both hands first, but I think it would just be something that would really make my life complete.

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