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  • Transcriber: Joseph Geni Reviewer: Camille Martínez

  • Memory is such an everyday thing that we almost take it for granted.

  • We all remember what we had for breakfast this morning

  • or what we did last weekend.

  • It's only when memory starts to fail

  • that we appreciate just how amazing it is

  • and how much we allow our past experiences to define us.

  • But memory is not always a good thing.

  • As the American poet and clergyman John Lancaster Spalding once said,

  • "As memory may be a paradise from which we cannot be driven,

  • it may also be a hell from which we cannot escape."

  • Many of us experience chapters of our lives

  • that we would prefer to never have happened.

  • It is estimated that nearly 90 percent of us

  • will experience some sort of traumatic event during our lifetimes.

  • Many of us will suffer acutely following these events and then recover,

  • maybe even become better people because of those experiences.

  • But some events are so extreme that many --

  • up to half of those who survive sexual violence, for example --

  • will go on to develop post-traumatic stress disorder,

  • or PTSD.

  • PTSD is a debilitating mental health condition

  • characterized by symptoms such as intense fear and anxiety

  • and flashbacks of the traumatic event.

  • These symptoms have a huge impact on a person's quality of life

  • and are often triggered by particular situations

  • or cues in that person's environment.

  • The responses to those cues may have been adaptive when they were first learned --

  • fear and diving for cover in a war zone, for example --

  • but in PTSD,

  • they continue to control behavior when it's no longer appropriate.

  • If a combat veteran returns home and is diving for cover

  • when he or she hears a car backfiring

  • or can't leave their own home because of intense anxiety,

  • then the responses to those cues, those memories,

  • have become what we would refer to as maladaptive.

  • In this way, we can think of PTSD as being a disorder of maladaptive memory.

  • Now, I should stop myself here,

  • because I'm talking about memory as if it's a single thing.

  • It isn't.

  • There are many different types of memory,

  • and these depend upon different circuits and regions within the brain.

  • As you can see, there are two major distinctions in our types of memory.

  • There are those memories that we're consciously aware of,

  • where we know we know

  • and that we can pass on in words.

  • This would include memories for facts and events.

  • Because we can declare these memories,

  • we refer to these as declarative memories.

  • The other type of memory is non-declarative.

  • These are memories where we often don't have conscious access

  • to the content of those memories

  • and that we can't pass on in words.

  • The classic example of a non-declarative memory

  • is the motor skill for riding a bike.

  • Now, this being Cambridge, the odds are that you can ride a bike.

  • You know what you're doing on two wheels.

  • But if I asked you to write me a list of instructions

  • that would teach me how to ride a bike,

  • as my four-year-old son did when we bought him a bike

  • for his last birthday,

  • you would really struggle to do that.

  • How should you sit on the bike so you're balanced?

  • How fast do you need to pedal so you're stable?

  • If a gust of wind comes at you,

  • which muscles should you tense and by how much

  • so that you don't get blown off?

  • I'll be staggered if you can give the answers to those questions.

  • But if you can ride a bike, you do have the answers,

  • you're just not consciously aware of them.

  • Getting back to PTSD,

  • another type of non-declarative memory

  • is emotional memory.

  • Now, this has a specific meaning in psychology

  • and refers to our ability to learn about cues in our environment

  • and their emotional and motivational significance.

  • What do I mean by that?

  • Well, think of a cue like the smell of baking bread,

  • or a more abstract cue like a 20-pound note.

  • Because these cues have been pegged with good things in the past,

  • we like them and we approach them.

  • Other cues, like the buzzing of a wasp, elicit very negative emotions

  • and quite dramatic avoidance behavior in some people.

  • Now, I hate wasps.

  • I can tell you that fact.

  • But what I can't give you are the non-declarative emotional memories

  • for how I react when there's a wasp nearby.

  • I can't give you the racing heart,

  • the sweaty palms, that sense of rising panic.

  • I can describe them to you,

  • but I can't give them to you.

  • Now, importantly, from the perspective of PTSD,

  • stress has very different effects on declarative and non-declarative memories

  • and the brain circuits and regions supporting them.

  • Emotional memory is supported by a small almond-shaped structure

  • called the amygdala

  • and its connections.

  • Declarative memory, especially the what, where and when of event memory,

  • is supported by a seahorse-shaped region of the brain

  • called the hippocampus.

  • The extreme levels of stress experienced during trauma

  • have very different effects on these two structures.

  • As you can see, as you increase a person's level of stress

  • from not stressful to slightly stressful,

  • the hippocampus,

  • acting to support the event memory,

  • increases in its activity

  • and works better to support the storage of that declarative memory.

  • But as you increase to moderately stressful, intensely stressful

  • and then extremely stressful, as would be found in trauma,

  • the hippocampus effectively shuts down.

  • This means that under the high levels of stress hormones

  • that are experienced during trauma,

  • we are not storing the details,

  • the specific details of what, where and when.

  • Now, while stress is doing that to the hippocampus,

  • look at what it does to the amygdala,

  • that structure important for the emotional, non-declarative memory.

  • Its activity gets stronger and stronger.

  • So what this leaves us with in PTSD

  • is an overly strong emotional -- in this case fear -- memory

  • that is not tied to a specific time or place,

  • because the hippocampus is not storing what, where and when.

  • In this way, these cues can control behavior

  • when it's no longer appropriate,

  • and that's how they become maladaptive.

  • So if we know that PTSD is due to maladaptive memories,

  • can we use that knowledge to improve treatment outcomes

  • for patients with PTSD?

  • A radical new approach being developed to treat post-traumatic stress disorder

  • aims to destroy those maladaptive emotional memories

  • that underlie the disorder.

  • This approach has only been considered a possibility

  • because of the profound changes in our understanding of memory

  • in recent years.

  • Traditionally, it was thought that making a memory

  • was like writing in a notebook in pen:

  • once the ink had dried, you couldn't change the information.

  • It was thought that all those structural changes

  • that happen in the brain to support the storage of memory

  • were finished within about six hours,

  • and after that, they were permanent.

  • This is known as the consolidation view.

  • However, more recent research suggests that making a memory

  • is actually more like writing in a word processor.

  • We initially make the memory and then we save it or store it.

  • But under the right conditions, we can edit that memory.

  • This reconsolidation view suggests that those structural changes

  • that happen in the brain to support memory

  • can be undone,

  • even for old memories.

  • Now, this editing process isn't happening all the time.

  • It only happens under very specific conditions

  • of memory retrieval.

  • So let's consider memory retrieval as being recalling the memory

  • or, like, opening the file.

  • Quite often, we are simply retrieving the memory.

  • We're opening the file as read-only.

  • But under the right conditions,

  • we can open that file in edit mode,

  • and then we can change the information.

  • In theory, we could delete the content of that file,

  • and when we press save,

  • that is how the file -- the memory --

  • persists.

  • Not only does this reconsolidation view

  • allow us to account for some of the quirks of memory,

  • like how we all sometimes misremember the past,

  • it also gives us a way to destroy those maladaptive fear memories

  • that underlie PTSD.

  • All we would need would be two things:

  • a way of making the memory unstable -- opening that file in edit mode --

  • and a way to delete the information.

  • We've made the most progress

  • with working out how to delete the information.

  • It was found fairly early on

  • that a drug widely prescribed to control blood pressure in humans --

  • a beta-blocker called Propranolol --

  • could be used to prevent the reconsolidation

  • of fear memories in rats.

  • If Propranolol was given while the memory was in edit mode,

  • rats behaved as if they were no longer afraid of a frightening trigger cue.

  • It was as if they had never learned to be afraid of that cue.

  • And this was with a drug that was safe for use in humans.

  • Now, not long after that,

  • it was shown that Propranolol could destroy fear memories in humans as well,

  • but critically, it only works if the memory is in edit mode.

  • Now, that study was with healthy human volunteers,

  • but it's important because it shows that the rat findings

  • can be extended to humans and ultimately, to human patients.

  • And with humans,

  • you can test whether destroying the non-declarative emotional memory

  • does anything to the declarative event memory.

  • And this is really interesting.

  • Even though people who were given Propranolol

  • while the memory was in edit mode

  • were no longer afraid of that frightening trigger cue,

  • they could still describe the relationship

  • between the cue and the frightening outcome.

  • It was as if they knew they should be afraid,

  • and yet they weren't.

  • This suggests that Propranolol can selectively target

  • the non-declarative emotional memory

  • but leave the declarative event memory intact.

  • But critically, Propranolol can only have any effect on the memory

  • if it's in edit mode.

  • So how do we make a memory unstable?

  • How do we get it into edit mode?

  • Well, my own lab has done quite a lot of work on this.

  • We know that it depends on introducing some but not too much new information

  • to be incorporated into the memory.

  • We know about the different chemicals the brain uses

  • to signal that a memory should be updated

  • and the file edited.

  • Now, our work is mostly in rats,

  • but other labs have found the same factors allow memories to be edited in humans,

  • even maladaptive memories like those underlying PTSD.

  • In fact, a number of labs in several different countries

  • have begun small-scale clinical trials of these memory-destroying treatments

  • for PTSD

  • and have found really promising results.

  • Now, these studies need replication on a larger scale,

  • but they show the promise of these memory-destroying treatments

  • for PTSD.

  • Maybe trauma memories do not need to be the hell from which we cannot escape.

  • Now, although this memory-destroying approach holds great promise,

  • that's not to say that it's straightforward

  • or without controversy.

  • Is it ethical to destroy memories?

  • What about things like eyewitness testimony?

  • What if you can't give someone Propranolol

  • because it would interfere with other medicines that they're taking?

  • Well, with respect to ethics and eyewitness testimony,

  • I would say the important point to remember

  • is the finding from that human study.

  • Because Propranolol is only acting on the non-declarative emotional memory,

  • it seems unlikely that it would affect eyewitness testimony,

  • which is based on declarative memory.

  • Essentially, what these memory-destroying treatments

  • are aiming to do

  • is to reduce the emotional memory,

  • not get rid of the trauma memory altogether.

  • This should make the responses of those with PTSD

  • more like those who have been through trauma

  • and not developed PTSD

  • than people who have never experienced trauma in the first place.

  • I think that most people would find that more ethically acceptable

  • than a treatment that aimed to create some sort of spotless mind.

  • What about Propranolol?

  • You can't give Propranolol to everyone,

  • and not everyone wants to take drugs to treat mental health conditions.

  • Well, here Tetris could be useful.

  • Yes, Tetris.