IRA FLATOW, host
What if frightening memories could be erased just by thinking about them? Well, a new study in the journal Nature suggests it might be possible for people to rewrite these fearful memories without drugs. What might this mean for the treatment of things like posttraumatic stress or anxiety disorders? That's what we're going to be talking about now with Elizabeth Phelps. She is professor in psychology department at New York University, and author on the paper. She's here in our New York studios. Welcome to the program.
Professor ELIZABETH PHELPS (Psychology, New York University): Thanks for having me, Ira.
FLATOW: Tell us about this study that you did. It had to do with shocking people.
Prof. PHELPS: It did. We shock people a lot in my lab.
(Soundbite of laughter)
Prof. PHELPS: And you're welcome to come any time. What we did in our lab, it was we created a fear memory. And we did this by giving somebody something neutral. In our case, it was a colored square, say, a blue square.
Prof. PHELPS: And we pair it with a mild shock to the wrist. And when we do this, eventually, or pretty quickly actually, you learn that the blue square means you might get a shock, so the blue square now predicts something dangerous. We can measure your body's response and we measure an indication of how much you sweat. And that's how we create a fear memory.
FLATOW: It's just like Pavlov with the rat.
Prof. PHELPS: It's exactly - it's identical to Pavlov.
FLATOW: Yeah. Yeah.
Prof. PHELPS: Yeah. But Pavlov used dogs.
Prof. PHELPS: The - and we use people in our study.
(Soundbite of laughter)
Prof. PHELPS: The - then what we do - in this particular study, what we were looking at was what happens now when you retrieve the memory later�
Prof. PHELPS: �and restore it. So one thing we know about memory is when you encounter something, it takes a period of time for the memory to become set in your mind. You're not doing anything, but there's processes going on in your brain that create a memory trace.
Prof. PHELPS: And we've known for a long time that, initially, when you learn something, if something would happen right afterwards, for instance, you had a concussion�
Prof. PHELPS: �you might forget what happened before and that's because you interfere with that process of storage that we call consolidation. There's recently been this renewed idea in this interest that now every time you retrieve a memory, it gets stored again. There's a process in the brain that takes time where the memory is stored. It's called reconsolidation.
Prof. PHELPS: And this presents a second opportunity where the memory is vulnerable. It's fragile. It can be disrupted.
Prof. PHELPS: So we took advantage of that idea. So we brought people in, we created this fear memory by pairing things like blue squares with shocks. The next day, we brought them in and we reminded them of the memory. Just gave you the blue square.
Prof. PHELPS: And what we did - there's lots of studies in rats showing that now if I injected a drug into this part of brain - of the brain called the amygdala where the memory is stored, I could disrupt the restorage process. We didn't do that because most of these drugs you wouldn't want to inject into your amygdala�
Prof. PHELPS: �in people. Instead, what we did is we took advantage of the idea that there's this vulnerability time. And during that time window, we taught you: now this thing is safe. And we did that by just presenting the blue square again and again and again, and nothing bad happened. And because we did that during this time where the memory was vulnerable, was susceptible, it actually changed the memory as it was being restored. And, now, subsequently, you didn't express the fear anymore.
FLATOW: Because you didn't get the shock at that point.
Prof. PHELPS: You didn't get the shock at that point. And, normally, if we do that, if we do that normally, that's called extinction.
Prof. PHELPS: It gets rid of the fear memory. The problem is when you do extinction and it's not during this specific time window�
FLATOW: And what window is that exactly?
Prof. PHELPS: The time window we think is, you know, there's only a few studies that�
Prof. PHELPS: �are out there. It takes about, you know, three minutes - we did 10 minutes for the window to open up - at least three minutes for the window to sort of open up.
Prof. PHELPS: And then it's open for like an hour. And by six hours, we know it's closed. So there's not a lot of studies exploring exactly what that window is.
Prof. PHELPS: There are none in people.
Prof. PHELPS: And it may not - people may not be like rats. And so, all we know at this point is it works for 10 minutes.
FLATOW: So if you came back 24 hours later, for example�
Prof. PHELPS: Mm-hmm.
FLATOW: �and did they come back eventually?
Prof. PHELPS: They came back 24 hours later.
FLATOW: And then you couldn't extinguish the memory.
Prof. PHELPS: No. Twenty-four hours later, what happened is they didn't express the fear at all.
Prof. PHELPS: A second group that got regular extinction training, this exact same procedure�
Prof. PHELPS: �but not in the window when the memory was vulnerable - so we didn't do the reminder.
FLATOW: I see.
Prof. PHELPS: They - for them, the fear response came back. And we brought them back a year later and the fear response came back with those guys again and still didn't come back with the folks that got the safe training during that specific time window.
FLATOW: Now how can we apply this, you know, to people in everyday life situation?
Prof. PHELPS: You know, that is, of course, I want to say $64,000 question�
Prof. PHELPS: �but it's actually more than that now.
(Soundbite of laughter)
FLATOW: I'm sure it is.
Prof. PHELPS: You know, all I can say at this point is, you know, we've done this simple study, one study in humans. The hope would be�
Prof. PHELPS: �by understanding the processes by which memories are vulnerable and susceptible and when they are, we can develop better therapeutic interventions. So what's interesting about this is all of this is based on a rich history of research with non-humans.
Prof. PHELPS: Looking at the, you know, molecular processes that occur in the brain when memories are stored. And it's because we have that knowledge that we can manipulate that here behaviorally�
Prof. PHELPS: �the same processes in humans. But, normally, when you have all that information, what you use it for is to develop drugs...
Prof. PHELPS: �to treat disorders.
Prof. PHELPS: This is telling us now if we can really understand how memories are formed, how they're stored, how they're restored, we can now use that not to develop drugs but to develop better behavioral interventions. So this would suggest maybe eventually�
Prof. PHELPS: �we can extend this to complicated situations and things like that, that, you know, we would think about the timing of therapeutic interventions, clinical interventions for disorders as a key factor in their ultimate success.
FLATOW: So it's like people who are beginning to use behavior modification�
Prof. PHELPS: Yes.
FLATOW: �instead of drugs�
Prof. PHELPS: yes.
FLATOW: �to treat some anxiety disorders and things like that.
Prof. PHELPS: Well, that's always been the case, right?
Prof. PHELPS: I mean, actually drugs are much more popular than they used to be.
FLATOW: Right. But you're saying we could go back to the old talking method maybe to solve somebody�
Prof. PHELPS: Yeah, I mean, this - these procedures you use to treat things like phobias.
Prof. PHELPS: They're exposure therapy, right? And they're based on the principles of extinction.
Prof. PHELPS: So if you, say, are afraid of snakes, what you would do if you had exposure therapy is you'd come into the clinic, they'd expose you to a picture of the snake, you'd learn to relax. So, you know, again, now you're encountering this in a safe environment. You know, then maybe they'd actually have a snake in a cage and, you know, you learn to relax. And so that's just based on extinction. This idea of extinction, you know, that Pavlov described very well has been used to treat anxiety disorders for a long time.
Prof. PHELPS: What's different about this is the problem with regular extinction is it creates two memories: this thing is fearful and this thing is safe. And those two compete. And so you get stressed out, so the fearful memory comes back.
Prof. PHELPS: And all this would suggest is that if we do that same type of training during a window where we know from all this beautiful animal work that the memory is vulnerable, we might actually rewrite the memory or change the memory in a more permanent fashion so the fear doesn't come back.
FLATOW: So to do that, I guess, practically, you'd have to know what the upper limit was on the time, right?
Prof. PHELPS: We need to know all of that. I mean, we'd need to know so much more than we know now. I mean, I just described to you the experiment. It was incredibly simple. We've only looked at 10 minutes. We know for rats it works out to an hour. We know by six hours, it's been too long. That's about it.
FLATOW: We're talking with Elizabeth Phelps on SCIENCE FRIDAY from NPR News, talking about - interesting. So what you're basically saying is now we have enough confidence that we - in this working that we can study it more in people.
Prof. PHELPS: Yes.
Prof. PHELPS: Yeah. So there's been some work with drugs and people trying to block memories�
Prof. PHELPS: �during this stage but they've been of mixed success.
Prof. PHELPS: And this was, you know, again, not other labs have done this so far as far as we know. It's not published, at least. But we've done a number of studies at this point and it seems to work on almost every single case.
FLATOW: Mm-hmm. Would it work for something like post-traumatic stress disorders?
Prof. PHELPS: That would be the hope, right. The hope would be - and exposure therapies treatment - based treatments is not - idea of extinction-based treatments is being used today with PTSD. So, you know, you bring the person into the clinic, they retrieve the memory in a safe environment, you know, by doing that a number of times, perhaps the memory loses some of its emotional power.
Prof. PHELPS: And that would be one of the hopes that it could be used for things like phobias and PTSD. But, you know, I'm a little reluctant to talk about that because, you know, there are people out there truly suffering�
Prof. PHELPS: �and it's premature to say that we - this would apply. There's so - those memories are so much more complicated�
Prof. PHELPS: �than a simple blue square. And knowing how to bring the memory to mind in a discrete way is going to be critical, knowing if you're highly stressed, does it not work�
Prof. PHELPS: �if you change the context.
FLATOW: Yeah. Yeah.
Prof. PHELPS: So, you know, those are the things we have to know.
FLATOW: So how do you move forward now? What would be the next line of attack?
Prof. PHELPS: Well - so one is to try to, you know, answer these questions, you know, about more complex memories. Another - what we're actually doing, the study that we're doing right now, we have two lines of research along this line. One is to try to understand the brain mechanisms better.
Prof. PHELPS: So one of the things we know is when you have these two memories competing in regular extinction training, that requires the prefrontal cortex to inhibit the amygdala where the memory is stored. And we think what we're doing here - and, again, we've only done behavior. We think we're rewriting the memory as it's stored in the amygdala. So what that would suggest, the prefrontal cortex wouldn't be involved when we change fear memories in this way.
FLATOW: Mm-hmm. Mm-hmm.
Prof. PHELPS: So we're doing a brain imaging study to see if that's the case, just to verify that we're doing something like we think we're doing because, again, we've just done this one particular paradigm.
Prof. PHELPS: And we're also still looking to see, you know, how the drugs that might work would, you know, could be more effective or understand why they're working sometimes and why they're not, you know, and get that as another assay into this process.
Prof. PHELPS: So, you know, but I think in the future, all these questions you're asking, you know, how do you extend this window out, is it going to be applicable to PTSD, you know, what about a complicated memory�
Prof. PHELPS: �how specific can we be in targeting memories, we have to ask those questions.
FLATOW: So, as you say, this is not just as simple as getting back on the horse after you've fallen.
Prof. PHELPS: Getting back on the horse is extinction training, right?
Prof. PHELPS: Getting - that's the exact principle, you know? The problem with things you fear is that you avoid them and you never have the opportunity for new experience. So that's extinction training. This is just saying: do this type of - this is safe training in a time window when you know the memory is vulnerable, and that's going to be a fairly specific time window. And, you know, there's a lot of research in rats that may not be exactly the same in people. Lots of things aren't between people and rats.
FLATOW: So you have to figure out when that window is.
Prof. PHELPS: We have to figure out when that window is. We know that so far our efforts based on what we know from rats were successful. But, again, it may not be exactly like it is in rats when we explore it more.
FLATOW: Mm-hmm. And that's basically - just thinking - this is a whole line of research.
Prof. PHELPS: It's a whole new line of research.
Prof. PHELPS: It's, you know, several doctoral dissertations.
(Soundbite of laughter)
FLATOW: And a lot of college students�
Prof. PHELPS: And a lot of college students.
FLATOW: �getting shocked. Did you use shocking for any one reason besides heed or anything else like that?
Prof. PHELPS: You know, it's just an effective way to get people afraid of the laboratory. And you know what, I'm just going to say, I have to mention, you know, we - they're mild shocks to the wrist. Everything is approved by the institutional review board and, essentially, we ask people to set the level themselves�
Prof. PHELPS: �what's uncomfortable but not painful.
FLATOW: I see.
Prof. PHELPS: And that's enough to generate autonomic nervous system around the fight or flight response, something like the fight or flight response.
FLATOW: Because I remember that study about people who would kill other people. It was a phony�
Prof. PHELPS: The Milgram study.
Prof. PHELPS: I know.
FLATOW: They would just keep turning the juice.
Prof. PHELPS: I used to do - I used to be a professor at Yale before NYU and we would - and we had a study where we just were telling people we'd shock them. And the institutional review board there actually made me shock people at the very end of the study even though I never had to.
Prof. PHELPS: You know, because it's worse to lie than shock them. And I think they were just - they had that Milgram history. Milgram worked at Yale, you know?
(Soundbite of laughter)
Prof. PHELPS: And they just were kind of scared of that.
FLATOW: All right. Well, I'm glad you got�
Prof. PHELPS: NYU will let me not shock people.
FLATOW: Okay. Good to know they're a little more benevolent. Thank you Elizabeth Phelps. Very interesting. Professor in psychology department at NYU and the author of this paper about fear. So thanks for taking time to be with us today.
Prof. PHELPS: Thanks for having me.
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