Date Published: October 30, 2019
Learning to overcome your fears is a key stepping stone to becoming resilient. But it’s easier said than done. Fear memories—from agonizing missteps to traumatic experiences—have a way of haunting us. On this special Halloween episode, Postdoctoral Fellow in the Department of Neuroscience at the Icahn s10投注网址 of Medicine at Mount Sinai, takes us inside the brain to understand why. Dr. Lacagnina’s work helps explain fear memories are so tenacious and raises the possibility of treating them with surgical precision.
You're listening to Road to Resilience. I'm Jon Earle. It's Halloween season again, the time of year when we go to elaborate lengths to feel afraid. With fear, though, comes the pleasure of overcoming fear. Think of a haunted house. You choose to go outside your comfort zone, you experience the thrill of fear, and at the end you emerge victorious. If only it were that easy in real life, where fears haunt and hem us in like the monster in a scary movie, even after the monster is gone. To become more resilient, we need to learn to face those fears. And to do that, it helps to understand what’s going on in your brain when you're afraid. With me to discuss how the brain processes fear is Dr. Anthony Lacagnina. He’s a neuroscientist in the Clem Lab here at the Icahn s10投注网址 of Medicine at Mount Sinai. He studies how fear memories are encoded and retrieved in the brain. His work may lead future treatments, including for post-traumatic stress disorder. In our conversation, Dr. Lacagnina describes your brain on fear and explains why some scary experiences give us a thrill while others traumatize. He also talks about how researchers are learning to switch fear memories on and off using techniques that raise big hopes and bigger questions. Anthony, it's so good to have you on Road to Resilience. Thanks so much for being on the podcast.
Dr. Anthony Lacagnina: 01:20
Happy to do it.
So you see a bear. What happens in your brain when you see a bear? You're in the forest, you're camping. Go.
Dr. Anthony Lacagnina: 01:26
So first you see the bear. You would probably think consciously, "Holy (bleep), there's a bear over there! What am I gonna do?" So we think what's going on would be visual information comes in. It's getting into the visual processing pathway. And then, at some point, also those things are going to converge into the amygdala, which for most people is the hub of this threat-detection center. And from there that information is also flowing into the cortex. And we think that the conscious expression of fear is going to be really governed by cortical activity -- this is going to be prefrontal cortex, associative cortices in the brain. And so now you're going to want to maybe run away and have the defensive responses, whether fight or flight -- that's going to kick in. You're going to now also have cascading physiological responses to help you survive. So you're going to have increased heart rate, dumping of adrenaline, and you have all those cascading effects.
Can you think of an experience from your life that was like that? Of "Oh, I experienced all those things" that you were just telling me about?
Dr. Anthony Lacagnina: 02:32
Yeah. I was spending time in Ecuador during my college years and there was a point where our guide there told us -- we lived right against a river -- and he was like, "Something some people like to do is go tubing on the river." So I convinced a couple friends to go down the river, and it was much faster than I than I expected. And what ended up happening was every little, tiny thing we saw downstream that even looked a little bit like a like a little whirlpool, I would freak out. And that happened maybe three or four times. And then finally, like the fourth time, it truly was -- like all the other ones were completely small compared to this one. It was this churning thing that, if we would have got sucked into it, we would have just been sucked down and killed. And so when I finally saw that from afar, I remember being like really scared.
Yeah. What determines whether, say, that experience on the river becomes an impediment in your future life or is just the scary thing that you're able to learn from?
Dr. Anthony Lacagnina: 03:31
s10投注网址 We know some of the ideas as to why fear, for example, or traumatic types of experiences would be, say, more potent. One could say just from an evolutionary perspective, knowing where the food is in your environment and where to get water and some of those things -- those are really important for survival and you need good memories of that. But you also need to always avoid a predator. That's a one-time thing. You can always find food somewhere else. So what's going on, like, why in the brain is it more robust? It might be that the threat-processing areas would form really strong memories. Another thing is -- when you have something that's really threatening, we know that there's also dumps of neurotransmitters, neuromodulators, even the adrenaline itself is going to, we think, obviously then interact with the brain and potentiates the types of learning. So it probably depends really on what an individual is experiencing at that moment. Like say you were in a combat situation as a soldier, and something happened to you that also triggered something that you had as a repressed memory of something in childhood, a very loud sound that at some point was very scary that you had even attributed and now you're re-experiencing that in another life-threatening scenario.
It's almost like they can compound.
Dr. Anthony Lacagnina: 04:56
s10投注网址 Yeah, those things would probably be reactivated. Those things might compound. And then the imprints of scary things, especially really traumatic ones, might be just stronger in the sense that the connections would be more strong, and they're also going to, again, be biased to be retrieved in order to promote survival.
s10投注网址 I mean that seems to make sense intuitively. It's the things that were true, scary, existential experiences would encode themselves more firmly than going to a haunted house and getting a fright.
Dr. Anthony Lacagnina: 05:28
Yeah, exactly. So real things that would -- like when you go to a haunted house, you really do know in the back of your head, "I'm not really in danger." It's a simulation of being in danger and, of course, that's kind of the trick. You still get scared when you go to a haunted house. I definitely do. Just jump-scares in general, it's impossible to suppress that, that's a reflex. But in the back of your head, you know. And we think, again, that that is top-down cortical and hippocampal-controlled context. You're contextualizing the experience. If something happens unexpected, you weren't prepared for that, and it might be in a context that you might even assume is safe. And that violation might cause a very strong learning that would potentially invade in the future.
s10投注网址 You were talking a moment ago about the importance of context and how the hippocampus imposes context and helps to prevent something that's merely scary from being traumatically so. Is there anything that can be done immediately after a traumatic event to lessen the chances that that becomes a problematic memory?
Dr. Anthony Lacagnina: 06:41
Yeah, this has actually been well-studied, and there was hope that maybe providing some kinds of therapy initially would be beneficial. One of the ones that are used very common is known as exposure therapy in which you would go through some kind of debriefing and almost be re-exposed to the traumatic experience. Unfortunately, sometimes treating things immediately afterwards has the opposite and unintended effect of promoting the fear to be more permanent. So this is obviously not what one would want to do. But the hope is that we think that memories are actually still kind of labile when they are not fully formed. And there's a process in the neuroscience field called "consolidation," where we think experiences in your life actually have to take time to make new connections with the previous connections in your brain. And this process, we think, takes potentially weeks to really like lay down what we call a long-term memory trace.
s10投注网址 So it sounds like that could be a window of opportunity for an intervention.
Dr. Anthony Lacagnina: 07:46
Yeah, that's been the thought for a long time. But there's actually a lot of really interesting work being done now that when the -- if the memory is even brought to the surface, even if it's a very, very long-term -- like a memory that's that happened years ago. There's chances that you can revive that memory and then intervene while the memory is again once plastic or once labile. And this is actually more thought -- has more potential in the sense that many people that go through traumatic experiences don't even want to address it or are maybe deny it or are focused on other things then, or even not have the resources to deal with treating it, or it happens to them at a young age. And so these are all problems that actually having therapies that could intervene much later would be almost -- would potentially be really useful for a broader population of people.
s10投注网址 What is a memory on a neurological level?
Dr. Anthony Lacagnina: 08:44
s10投注网址 Yeah, that's the million-dollar question! I would love to have a good solid answer to that. We have no clear idea, but I will give you a more satisfying answer which is -- we thought in the in the past that a memory would just be a stable -- like there'd be five neurons in your brain that would be, like, your grandma's birthday. And if you could get if you could activate those you would always remember that experience. It turns out a memory might be not in particular neurons themselves -- like just one or two -- but maybe in webs or collections of neurons that would -- there would be mechanisms to give you more and more refined detail. And that's really kind of like, again, to go back to treating traumatic experiences, we think that those probably are laid down in a very strong pattern that unfortunately can be reactivated by things that maybe aren't necessarily related to it, or that you fail at contextualizing appropriately. And so one that had something traumatic happened to them might -- something that would be benign and even though they know they're in a safe environment they can't help but have that that response. And so figuring out ways to get over that is where the field is trying to get to and we've made some progress, but there's still tons of work to be done.
s10投注网址 Right. Which brings us to the idea of potentially, hopefully extinguishing fear memory.
Dr. Anthony Lacagnina: 10:15
Yeah. So this is what my work was focused on. So there's some work that had been done that was -- through a bunch of really fancy genetic techniques that I could go into in depth if you want me to -- but let's just say they were able to capture all the neurons that were active during an experience and what they could do was in the future if they stimulated them using a technique called "optogenetics," they could basically reactivate only the neurons that were active prior -- like in that negative experience -- and the animal would behave as if it was remembering that experience. So the animal even though it was in a totally safe environment, you would stimulate these neurons and the animal's behavior would start showing that they were afraid.
s10投注网址 You were able to stimulate the memory itself. Like the fear network that we were talking about that is the memory.
Dr. Anthony Lacagnina: 11:04
Yes. That's what they would like to say. And we can claim -- as scientists we like to be very clear on what was going on and, you know, we could say, "When those neurons were stimulated the animal behaved as if it was remembering," you know, like, we don't really know it's conscious experience of that, of course.
What do we know now about stimulating the extinction memories and harnessing those to combat fear memories?
Dr. Anthony Lacagnina: 11:29
Based on both of those works – that maybe fear experiences and then suppressing that fear, that extinction memory, were maybe encoded in different populations of neurons – I went about it with that same approach where I put animals in a little context and I would, again, capture all the neurons that were active either during the negative experience, or what I did was I took a separate group of animals, I put them through that negative experience, and then I gave them that exposure or extinction training by putting them in the box over and over again, and their fear eventually declined. And now when I would put them in the box, they didn't have any response to it. Then what I did was I captured on one of the days when they were suppressing their fear pretty successfully, I captured those neurons. So now I ask the question – it's the same brain region, but it's capturing different populations of neurons, one active during fear and one active during suppression of that fear. And I found that they had completely opposite effects when I stimulated or I silenced those neurons. So, for example, if I stimulated the fear neurons, I replicated what previous work had shown, which is that the animals, even in a neutral completely safe environment, they would actually express that kind of fearful response. But if I stimulated the safe or extinction – I like to sometimes just call them the "safe neurons" – if I simulated the safe neurons, the animals would – if they were in a safe environment, it wouldn't do anything because they're not afraid of that area. But if they were back in that environment where it was scary to them, if I stimulated the extinction memory neurons, the animals would not relapse. They would have much less fear than the ones that I didn't do that on.
s10投注网址 Are you saying you were able to cure the fear in the mice?
Dr. Anthony Lacagnina: 13:21
Yes, let's say that so I get all the money in the future now. Yes. I mean, yes, we prevented relapse in these mice by stimulating the neurons that were active during that suppression memory. And this is what I think has a lot of interesting potential therapeutics, right. If they're in separate populations of neurons and we could even get somebody to go through a therapy session in which they were successful at suppressing their fear. If we could figure out and capture those neurons or strengthen the connections of them, maybe we can find ways to get over that biological crutch and make those memories stronger. And so this is, I think, the therapeutic potential of this type of research.
s10投注网址 What are the steps between where we are right now and a potential therapy? Like what do we still have to understand?
Dr. Anthony Lacagnina: 14:19
s10投注网址 To get to actual treatment in the in a human we need to be, obviously, really cautious. Doing any – especially any real manipulation or intervention – is no laughing matter, because you could have unintended consequences. And especially if you're dealing with traumatic types of memories, there'd be nothing worse than intervening, trying to turn up the safe memory and accidentally doing the opposite. But the reality is that people are hungry for therapies, and they want – people are even hungry for experimental therapies. They're asking the scientists, "Please. My depression, my PTSD is life-crippling. I would love it anything to help me at this moment." And so I think we need to start going faster and sooner in terms of experimenting and trying these things out. I think we're still a little far away from it. But I think the advent of a lot of these non-invasive brain-manipulating types of devices and – because the way that now for any kind of brain therapy is you have to go through brain surgery and stick an electrode in the brain and stimulate it. If we could figure out ways to focus magnetic waves, potentially acoustic sound waves – any of these things that could potentially be possible to get specific subtypes of neurons to be strengthened or weakened. I think that's going to be a very – like that will be a game changer. Yeah, that's the future I envision.
Well, now you've got me in sci-fi mode because I'm thinking of going to the drugstore and getting the "bear treatment" if you've had a bear experience, or getting the "PTSD treatment" if you've had a PTSD experience.
Dr. Anthony Lacagnina: 15:59
s10投注网址 You want the scary one, or you want you want to kill that?
I want to kill that. [laughs]
Dr. Anthony Lacagnina: 16:03
Okay. I thought you were like, "I just want to get the bear experience!"
This is fascinating stuff. Thanks so much Anthony, it's been a pleasure.
Dr. Anthony Lacagnina: 16:11
Thank you. Great talking to you.
That’s all for this episode of Road to Resilience. If you enjoyed the podcast, please rate and review us on Apple podcasts. And if you’ve got a few minutes, please fill out the listener survey on our website. It helps us understand you’re interested in. Road to Resilience a production of the Icahn s10投注网址 of Medicine at Mount Sinai. Our team includes Katie Ullman, Nicci Hudson, and me, Jon Earle. Justin Gunn shoots video for us, and Cathy Clarke shoots photographs for our website. Our executive producers are Dorie Klissas and Lucia Lee. From all of us here, thanks for listening. We'll see you next time. Anthony, tell me about your favorite film, your favorite scary movie?
Dr. Anthony Lacagnina: 16:49
Oh, scary movie. Hmm. Okay. I think one of my favorites is "Alien," and I just have a visceral memory. I think it honestly was the first movie that made me terrified. I watched it maybe when I was eight years old, or nine. And the iconic chest-bursting scene, I think I ran out of the room screaming and hid under my bed or something. So yeah, I still do that every time I watch the movie. No. [laughs]. But I love it. It's great.