Bringing an old memory back to mind would, you might think, strengthen it. But not so – when memories are recalled, they enter a surprisingly vulnerable state, when they can be reshaped or even rewritten. It takes a while for the memory to become strengthened anew, through a process called reconsolidation. Memories aren’t just written once, but every time we remember them.
This system allows us to rapidly update our memories with new information, for a more flexible and adaptable brain. It also means that the very act of remembering provides a valuable window of opportunity, during which memory can be manipulated. Now, a group of US scientists have done just that, exploiting this window to remove a simple fearful memory using fresh information, rather than drugs or invasive surgery.
Daniela Schiller from New York University trained volunteers to fear a coloured square by pairing it with a mild electric shock (the “acquisition” part of the graph below). The next day, Schiller reactivated their fear memories by once again showing them the shocking squares. When they did, their skin betrayed their nervousness by becoming better at conducting electricity, a sure sign that they were sweating.
Schiller then tried to extinguish their fearful responses with “extinction trials”, where they repeatedly saw the square without any shocks. This procedure ought to break the first day’s conditioning and it did temporarily (the “extinction” part of the graph below). But fear memories are harder to banish than that. On the third day, the volunteers were once again exposed to the scary squares, which, once again, sent most of them into a nervous sweat (the “re-extinction” part).
The only exceptions were the people whose memories of their conditioning had been reactivated 10 minutes before they went through the extinction training. If Schiller left a gap of 6 hours, or if she took the recruits straight into the extinction trials, they still reacted nervously to the squares. These results fit with the idea of reconsolidation, where remembering a memory provides a short window of opportunity for overwriting it. Doing so produces an anti-fear blockade that lasts much longer than 24 hours.
Schiller invited her volunteers back a year later, and 19 out of 65 returned. She gave them four shocks and showed them the coloured squares again – a powerful procedure that should have dramatically reinstated the fears they had been conditioned with a year before. But those whose fear memories had been overwritten didn’t succumb, while volunteers who previously belonged to the 6-hour or the no-reminder groups quickly started to get nervous again.
Best of all, Schiller found that the effect of the fear blockade was very specific. In a second experiment, she paired two squares of different colours (CSa and CSb in the graph below) with electric shocks. But she only reminded her volunteers about one of them before trying to wipe their fears away. And as predicted, a day later, only the fear memory that had been reactivated had been eventually blocked. While this is a fairly simplistic scenario, the specific nature of the effect is a must if any realistic application is to come of this one day. In real life, scary memories are associated with many possible triggers and not just coloured squares.
This study is a sequel. Earlier this year, Joseph Le Doux, whose lab Schiller works in, published similar results showing that the same technique was successful in rats. They conditioned rats to link a tone with electric shocks and then erased that memory in the same way that they did for the human volunteers – they reminded the rats of the tone to open the reconsolidation window, and then used the time to overwrite their conditioning using a shock-free tone. As with humans, the timing was crucial.
Other studies have used drugs to the same ends but many of these have been toxic. The only promising drug, the beta-blocker propanolol, was the star of a media circus earlier this year. Merel Kindt showed that propanolol could erase the emotional sting of a fearful memory. The research exploited reconsolidation windows, just as Schiller’s study did. By giving propanolol to people before they recalled a scary spider memory, Kindt could erase the fearful response it triggered.
Schiller says that it would be better to use methods that don’t involve drugs because of any potential side effects. But Kindt isn’t entirely convinced by these new experiments. She told me that a person’s sweaty skin tells you about whether they expect something bad to happen but not whether they’re afraid of it. In her experiment, she measured fearful responses by looking at the startle reflex – how strongly people blink to the terror in question.
Schiller may have more work to do to convince her critics but, at the very least, her study provides more evidence that reconsolidation is something that could be manipulated to treat anxiety disorders or PTSD. Drugs don’t have to be the solution – earlier this year, British researchers showed that playing Tetris can stop traumatic memories from consolidating in the first place. Perhaps the famously addictive game could be used to interfere with reconsolidation too.
Ironically enough, studies like these often provoke fear and panic that they will fall into the wrong hands. Outraged editorials often follow, chiding us that fearful memories are useful things to have because they remind us not to poke that tiger or touch that flame. Indeed, there’s evidence that our brain actively protects such memories, shielding them in a net of guardian molecules. Manipulating such systems is to play God with people’s mind.
But such criticisms miss the point. For a start, the benefits of remembering fearful experiences can often lead to the extreme drawbacks of anxiety or post-traumatic stress disorder. But perhaps most importantly, the entire point of reconsolidation is to allow the brain to incorporate new data into its existing framework. All these studies are doing is to give it the right information at the right time, nothing more than an advert or a classroom seeks to do.
Reference: Nature doi:10.1038/nature08637
More on memories:
As sufferers of post-traumatic stress syndrome know all too well, frightening experiences can be strong, long-lasting and notoriously difficult to erase. Now, we’re starting to understand why. Far from trying to purge these memories, the brain actively protects them by hiring a group of molecular bodyguards called CSPGs (or chondroitin sulphate proteoglycans in full).
By studying the brains of rats, Nadine Gogolla from Harvard University found that CSPGs – large chains of sugars and proteins – accumulate in the space around nerve cells and form defensive nets around a select few. Dissolve these nets, and the rats’ fearful memories were more easily erased.
The nets start to form round about the time when rats reach adulthood and their fearful memories become harder to erase. As adults, rats can learn to be scared of an inoffensive sensation, like the sound of a buzzer, for the rest of their lives, if it’s paired with an unpleasant one, like an electric shock.
However, the strength of this terror starts to wane if the rats repeatedly hear the ominous buzz without any nasty consequences. This process is called extinction, but it’s nowhere near as permanent or robust as the creation of the original fear. The minute the shock returns, the fear response recovers. This happens so quickly that the memory clearly hadn’t been erased or overwritten – the rat had merely learned to block it out.
Things are different in puphood. Before their third week of life, a rat’s fear memories can be easily erased; only afterwards do they become indelible. Gogolla thinks that the nets are the reason why. She looked at the brains of baby rats in their first month of life, and focused on their amygdala, a pair of almond-shaped structures that have roles in processing emotions. The number of CSPG nets in these regions shot up as the days went past, but particularly in the third week, when the switch from erasable fear memories to permanent ones takes place. That’s no coincidence.
A couple of weeks ago, I wrote about propranolol, a drug that can erase the emotion of fearful memories. When volunteers take the drug before recalling a scary memory about a spider, it dulled the emotional sting of future recollections. It’s not, however, a mind-wiping pill in the traditional science-fiction sense, and it can’t erase memories as was so widely reported by the hysterical mainstream media.
The research that’s published today is a different story. Jin-Hee Han from the University of Toronto has indeed found a way to erase a specific fearful memory, but despite the superficial similarities, this is a very different story to the propranolol saga. For a start, Han worked in mice not humans. And unlike the propranolol researchers, who were interested in developing ways of treating people with post-traumatic stress disorder, Han’s goal was to understand how memories are stored in the brain. Erasing them was just a step towards doing that.
Han’s found that a protein called CREB is a molecular beacon that singles out neurons involved in remembering fearful experiences. When a rat experiences something scary, the CREB-neurons in a part of its brain called the amygdala are responsible for storing that memory – for producing what neuroscientists call its “trace”. When Han killed the amygdala’s CREB-neurons, he triggered selective amnesia in the rats, abolishing the specific fears they had been trained to feel. The memory loss was permanent.
This is a major piece of work. Scientists have long believed that memories are represented by specific collections of neurons. But these neurons don’t occur in a neat, tidy clump; they’re often widely spread out, which makes finding the cells that make up any particular memory incredibly challenging. Han has done this by using the CREB protein as a marker. And in doing so, he had highlighted the vital role of this protein in our memories.
I stress again that this isn’t about erasing memories in and of itself. Doing so is just a means to an end – identifying a group of neurons involved in storing a specific memory. For reasons that should become clear in this article, Han’s technique isn’t exactly feasible in humans! Whether this will stop the inevitable run-for-the-hills editorials is perhaps unlikely, but enough speculation: on with the details.
If you wanted to turn a rat into a fearless critter, unfazed by cats or bigger rats, the best way would be to neutralise a small pair of tiny structures in its brain called the dorsal premammillary nuclei, orPMD. According to new research by Simone Motta at the University of Sao Paolo, these small regions, nestled within a rat’s hypothalamus, control its defensive instincts to both predators and other rats.
But not all neurons in the PMD are equal. It turns out that the structures are partitioned so that different bits respond to different threats. The front and side parts (the ventrolateral area) are concerned with threats from dominant and aggressive members of the same species. On the other hand, the rear and middle parts (the dorsomedial area) process the threats of cats and other predators. And both areas are distinct from other networks that deal with the fear of painful experiences, such as electric shocks.
This complexity is surprising. Until now, scientists have mostly studied the brain’s fear system by focusing on an area called the amydgala, which plays a role in processing memories of emotional reactions. And they have generally assumed that fearful responses are driven by the same networks of neurons, regardless of the threat’s nature.
There’s good reason to think that. Hesitating in the face of danger is a sure-fire way to lose one’s life, so animals respond in a limited number of instinctive ways when danger threatens. They freeze to avoid detection, flee to outrun the threat, or fight to confront it. These automatic “freeze, fight or flight” responses are used regardless of the nature of the threat. Rats, for example, behave in much the same way when they are menaced by cats or electrified floors alike, and actually find it very difficult to do anything else.
This limited repertoire of action convinced scientists that animals process different fears in the same way, relying on the same network of neurons to save their hides from any and all threats. Motta’s research shows that this idea is wrong, certainly for rats and probably for other mammals too. The brain’s fear system isn’t a one-size-fits-all toolkit; it has different compartments that respond specifically to different classes of threats.
The mainstream media are just queuing up to fail in their reporting of the propranolol story from a couple of days ago. To reiterate:
Propranolol is commonly used to treat high blood pressure and prevent migraines in children. But Merel Kindt and colleagues from the University of Amsterdam have found that it can do much more. By giving it to people before they recalled a scary memory about a spider, they could erase the fearful response it triggered.
The critical thing about the study is that the entire memory hadn’t been erased in a typical sci-fi way. Kindt had trained the volunteers to be fearful of spidery images by pairing them with electric shocks. Even after they’d been given propranolol, they still expected to receive a shock when they saw a picture of a spider – they just weren’t afraid of the prospect. The drug hadn’t so much erased their memories, as dulled their emotional sting. It’s more like removing all the formatting from a Word document than deleting the entire file.
The drug is not a “memory-wiping pill” (Guardian). It cannot “erase bad/painful memories” (Sun/ Fox News/ Metro/ Daily Mail) and it won’t give you a “spotless mind” (Scotsman). Perhaps it’s unsurprising given that massive wire agencies said similar things. The Press Association led with claims that the drug can “erase fearful memories“. Reuters at least said more cautiously that it was a “step towards erasing bad memories“.
To quote the person who actually did the research (and thanks Merel for chiming in on the earlier post):
“There was no memory erasure, just elimination of the fearful response.”
The problem with all of this, of course, is that people have straw-manned the research and are falling over themselves to publish trite editorials that (a) are irrelevant to the actual study and (b) serve to stoke public outrage over an ethical dilemma of their own concoction.
There are exceptions. The Boston Globe got it right and has a brilliant bit at the end that lays out in four simple sentences the bottom line, cautions, what’s next, and where the research was published. It has however accompanied the article with an incongruous photo of a koala, presumably some sort of mix-up with the Australian bushfire story.
The mental health charity MIND released a long and well-considered statement, which showed that they had actually read the paper and understood the science. The charity’s CEO, Paul Farmer, said:
“This is fascinating research that could transform the treatment for phobias and post traumatic stress disorder. Around 10 million people in the UK have a phobia and about 3.5% of the population will be affected by post traumatic stress disorder at some point yet our understanding of how to treat these conditions is still limited. While we welcome any advancement in this field we should also exercise caution before heralding this as a miracle cure.
“Eradicating emotional responses is clearly an area we would need to be very careful about. It could affect people’s ability to respond to dangerous situations in the future and could even take away people’s positive memories. We would not want to see an ‘accelerated Alzheimer’s’ approach.
“We still have limited research on how to treat complex mental health problems, with the focus often on pharmacological solutions. Drugs are a somewhat sledgehammer approach and can have unintended consequences. We know from other psychiatric drugs, for example antipsychotics and antidepressants, that individuals react in hugely varied ways to treatments and are often vulnerable to unpleasant side effects.
“We would need to see much more research into the risks and benefits into this treatment before it becomes a reality.”
All of that was culled by the BBC into the following:
But British experts questioned the ethics of tampering with the mind.
Paul Farmer, chief executive of mental health charity Mind, said he was concerned about the “fundamentally pharmacological” approach to people with problems such as phobias and anxiety.
He said the procedure might also alter good memories and warned against an “accelerated Alzheimer’s” approach.
Do you think it carries the same meaning or sense?
The wiping of unwanted memories is a common staple of science-fiction and if you believe this weekend’s headlines, you might think that the prospect has just become a reality. The Press Association said that a “drug helps erase fearful memories“, while the ever-hyperbolic Daily Mail talked about a “pill to erase bad memories“. The comparisons to The Eternal Sunshine of the Spotless Mind were inevitable, but the actual study, while fascinating and important, isn’t quite the mind-wiper these headlines might have you believe.
The drug in question is propranolol, commonly used to treat high blood pressure and prevent migraines in children. But Merel Kindt and colleagues from the University of Amsterdam have found that it can do much more. By giving it to people before they recalled a scary memory about a spider, they could erase the fearful response it triggered.
The critical thing about the study is that the entire memory hadn’t been erased in a typical sci-fi way. Kindt had trained the volunteers to be fearful of spidery images by pairing them with electric shocks. Even after they’d been given propranolol, they still expected to receive a shock when they saw a picture of a spider – they just weren’t afraid of the prospect. The drug hadn’t so much erased their memories, as dulled their emotional sting. It’s more like removing all the formatting from a Word document than deleting the entire file. Congatulations to Forbes and Science News who actually got it right.
Kindt’s work hinges on the fact that memories of past fears aren’t as fixed as previously thought. When they are brought back to mind, proteins at the synapses – the junctions between two nerve cells – are broken down and have to be created from scratch. This process is called “reconsolidation” and scientists believe that it helps to incorporate new information into existing memories. The upshot is that when we recall old memories, they have to be rebuilt on some level, which creates an opportunity for changing them.
A few years ago, two American scientists managed to use propranolol to banish fearful responses in rats. They injected the animals in their amygdalae, a part of their brains involved in processing emotional memories. The drug didn’t stop a fearful memory from forming in the first place, but it did impair the memory when the rats tried to retrieve it. Now, Kindt has shown that the chemical has the same effect in humans.