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When it comes to the study of memory, we might be living in something of a golden age. Researchers are exploring provocative questions about what memory fundamentally isand how it might be manipulated. Some scientists are tweaking the brains of lab rats in order to remove memories or implant false ones. Others are looking into how memory might be enhanced. Such research often sounds creepy, but it could lead to ways of staving off dementia, neutralizing post-traumatic stress disorder, reducing anxiety, treating depression, or curbing addiction.

Much of this work is possible because neuroscientists have realized that memory is more plastic than previously thought. Think of something that you did long agoon a sunny afternoon when you were a child, let’s say. Does your brain rummage around for that memory, show it to you, and put it back intact, as you might do with a photograph in a trunk in the attic? For decades, the prevailing answer was essentially yesthat strong memories were “consolidated” in the brain and remained static. But it now appears the opposite is true: every time you remember something, your brain rewrites or “reconsolidates” the memory. Your memory of any sunny day in your childhood is merely a version of the last time you thought about it.

Among the stunning implications is that intervening in the reconsolidation process can alter a memory and change how it feels. Some of the most intriguing research on this idea has been led by Joseph LeDoux, a neuroscientist who has been working since the 1970s to investigate how processes in the brain generate emotions. In recent years, he and colleagues have investigated whether giving people an antianxiety drug as they recall a traumatic experience can reduce the dread they feel upon further recollections. If it works, it could be one of many opportunities for reshaping memory, as LeDoux told MIT Technology Review’s deputy editor, Brian Bergstein, in his NYU office.

Giving people a pill as they reconsolidate a troubling memory sounds like an elegant treatment for PTSD and other disorders. How well has the research progressed?

The idea is still viable. The drug that’s going to do the trick in humanswe don’t yet know what it is.

Why not the antianxiety drug propranolol, which has been used in several experiments?

We know this thing works very well in rats. [In humans] there’s been some success, but it doesn’t seem that’s actually going to be a very robust solution.

What are the prospects for improving the memory of people with dementiaor any of us, for that matter?

The issue you get at whenever you’re dealing with a memory failure of any kind is: is the problem an inability to retrieve a memory that’s there, or is it that the memory is no longer there and by no means could you retrieve it? And it’s definitely the case that we have retrieval problems, right? You can’t remember something, you kind of know it’s there, and then a couple of hours later it pops up. There is stuff in our brain that we can’t easily retrieve. I think that’s where there’s hope. You can do things that would facilitate the retrieval process.

What might that be?

The simplest idea would be that it’s a problem of low arousal in the brain. We know that emotionally arousing situations are more likely to be remembered than mundane ones. A big part of the reason for this is that in significant situations chemicals called neuromodulators are released, and they enhance the memory storage process. The brain is more alert and attentive. All the spokes are working and all the gears are oiled.

So could we develop memory vitamins that offer that same boost?

[The effects of the neuromodulators] can be mimicked with drugs that do the same thing. Or if you want to remember something, put the information in a significant context. In other words, make it meaningful by thinking of it in a way that adds some positive or negative charge, or by doing something that increases your level of arousal—exercise, for example.

Would a memory prosthetic be possiblesomething put into the brain to restore lost memories in someone with dementia or a brain injury?

DARPA [the U.S. military’s R&D agency] seems to be going full steam ahead on these kinds of technologies. What they plan to do is put chips in [the brain]. It would be like a prosthesis—instead of moving your arm, you’re fixing memory. I have no idea how they would achieve that.

We don’t know the route to get there?

I don’t know the route.

Memory is, first of all, not in one spot—it’s distributed across probably multiple brain areas, many millions of synapses in those brain areas. So I don’t know how you reconfigure it, fix it. I don’t know how you regenerate the right patterns of connectivity. I don’t think you could restore lost memories. But what you might conceivably do is restore some ability to store new memories.

“You can’t remember something, you kind of know it’s there, and then a couple of hours later it pops up. There is stuff in our brain that we can’t easily retrieve. I think that’s where there’s hope. You can do things that would facilitate the retrieval process.”

Messing with memory is a huge deal. It goes to the core of who we are. Treating PTSD would be wonderful, but isn’t it also possible to make people artificial Pollyannas?

Or fearless monsters. There’s always going to be ethical implications. But we’ll just have to sort that out.

When we first published this work [on reconsolidation], someone wrote a commentary in the New York Times saying, “Let’s say you were a Holocaust survivor. You lived 50 years with these awful memories, and all of a sudden you’re erasing memories of the Holocaust. What would that do to your personality? It’s who you are now.” [After further research], the conclusion that we came up with is that a patient and therapist would have to slowly chip away at a memory to a level they were comfortable with. [And] the research so far suggests it reduces the zing, takes the emotional valence out of the situation, rather than erases the memory itself.

The other side of that is you can also intensify memories. So we did studies in rats where we give them propranolol, and that weakens the memory. But if you give them ­isoproterenol [which has the opposite effect on the brain’s neurostimulators], the memory is now stronger. If you have some way to strengthen memory after retrieval, it could be stronger and better.

What’s a situation in which people would want to do that?

In general, people who have sluggish memories, they’re not forming memories very well. Were they to be on a low dose of isoproterenol, they might get a little extra boost.

The other idea is that we might be able to give people positive experiences and a shot of isoproterenol, and store those instead of negative experiences.

You could build up more positive memories in them?

Right, right.

I imagine that could be useful in helping people struggling with depression.

And as far as I know it’s never been done. It’s doable.

So why hasn’t it been done?

Well, you know, I had the idea a while ago, and then I kind of forgot about it. And now the memory of itmaybe I’ll think about doing something. [He laughs.]

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Tagged: Biomedicine, EmTech2014

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