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How to forget fear – Times Online

direct reprint from How to forget fear – Times Online.

Imagine if you could rewrite your mind as quickly as a document on your computer. No more painful memories, no phobias or ingrained fears, just a blank slate where the scars that mark each human life used to be. This may sound like the stuff of Hollywood fantasy but last month it came a step closer to reality at New York University. By manipulating memory a research team managed to remove a conditioned fear response among volunteers. As scientists learn more about the mechanics of the mind, such targeting and erasing of traumatic recollections will become easier and easier.

Fear tortures all of us in one form or another. The Ancient Greeks blamed sudden knee-knocking terror on a lecherous, goatish divinity, Pan. While his ability to inspire panic was enough to rout the Titans, the force behind it was too mysterious for mere mortals to comprehend. But they knew it when they felt it.

We all recognise the physiological symptoms when danger threatens: our stomachs lurch and adrenalin fires up our muscles. Charles Darwin chronicled this in The Expression of the Emotions in Man and Animal: “. . . the eyes and mouth are widely opened, and the eyebrows raised. The frightened man at first stands like a statue motionless and breathless, or crouches down as if instinctively to escape observation.”

These reactions are triggered by both memory and instinct. Evolution has endowed us with innate impulses that warn against age-old dangers. Thus spiders or snakes may set our pulses racing, but most of our anxieties are learnt through experience. We recall that something hurt or scared us and these memories help to trigger our nervous system. Neuroscience suggests that both reactions can be traced back to a small almond-shaped part of the human brain, the amygdala. It plays a key role in responding to stimuli, recognising danger from previous situations and sounding the alert.

How we recall fear has fascinated scientists for centuries. In 1920, the unfortunate “Little Albert” was one of the early targets for experimentation. Over several months the baby boy became a guinea pig for scientists at Johns Hopkins University in Baltimore. Their aim? To try to condition fear. First, the researchers placed a white rat in front of the baby. This didn’t scare him. Then they linked the appearance of the rodent with a loud bang. After exposure to this combination, Albert began to weep on cue when he saw the rat alone. Their report suggests that his reaction to white fur became so extreme that even a Father Christmas mask induced fear.

Albert’s mother never gave consent, rendering these experiments highly unethical by today’s standards. That said, current approaches are not dissimilar, simply more sophisticated and informed. Last year Merel Kindt and her team at the University of Amsterdam experimented with chemical intervention to dull the emotional sting of a scary memory. Kindt made her considerably more adult Little Alberts anxious by showing them images of spiders and giving them mild electric shocks at the same time. She found that if they took a beta-blocker, propanolol, before reminiscing about their experience, they were no longer scared of the spider images.

This experiment capitalised on the knowledge that traumatic memories are not written just once but every time we remember them. When we first record memories the presence of certain proteins strengthens connections between the synapses — the gaps between nerve cells — in the brain. However, every time we recall these memories subsequently the proteins break down and must be remade from scratch. During this period of reconsolidation our memory is vulnerable to reshaping. Like that open Word document on your laptop, it can be rewritten.

When Kindt gave propanolol to her volunteers she managed to interfere with the process of reconsolidation. If her team didn’t reactivate volunteer memories by showing them the spider pictures, the drug did nothing. But if the spider triggered a fearful response, thus opening the reconsolidation window, the drug managed to interfere with it. Propanolol did not erase these memories; it simply blunted their emotional edge. While the volunteers still expected a shock, they were not scared by the prospect.

The ability to update our memories with new information highlights the flexibility of our brain. Every act of remembering gives us an opportunity to shape memories, or even erase them. The discovery of the reconsolidation window has kick-started a lot of new memory research, advances in which could have important implications for people who suffer from unwanted fearful memories. Potential treatments for anxiety, phobias or post-traumatic stress disorder (PTSD) may be close at hand. Propanolol, or other chemicals that do the same job more effectively, could help sufferers to get on with their lives more easily. These discoveries could have much wider applications than removing fear: for instance, in people who struggle to control their impulses, they may help to erase addictions.

But the possibility of removing past fears ramps up new concerns about ethics, with strident editorials decrying attempts to meddle with the human mind. The most extreme writers describe the research as “threats to human identity” and “the stuff of science-fiction nightmares”. There are inevitable comparisons with the film Eternal Sunshine of the Spotless Mind, in which mind-wiping technology robbed characters of the experiences that enrich our lives and make us human.

These concerns are overblown where propanolol is concerned. The drug merely changes the emotional content of memories, rather than erasing them. Scientists are well aware that fear is a vital teacher: moments of fright are how we learn about dangers. That memory of what went wrong last time we left the stove on can stop us from making costly, even lethal, mistakes.

Our brain goes to some trouble to solidify such recollections. Memories of shocking or traumatic events are sometimes known as “flashbulb memories” because of their exceptional vividness. Our bodies even offer them special protection through molecules called CSPGs, which act like bodyguards. Last year, scientists at Harvard University showed that large chains of proteins and sugars form defensive nets around specific nerve cells, protecting the memories encoded within from being lost.

Tampering with such important memories, unwanted though they may be, is clearly not something we should undertake lightly. Indeed the act of changing the emotional intensity of scary memories, as propanolol can do, could have legal implications. If victims of crime use the drug to reduce their stress, it could be tantamount to tampering with evidence. The dulled emotional content of medicated recollections may hamper the ability to make a solid case in court, and doctors who prescribe the drug could be accused of obstructing justice.

Many of these worries stem from our unease over the use of mind-altering pills. We forget that chemicals are only one method of playing with our minds. The point of the reconsolidation period is to allow the brain to incorporate new data into its framework. This means that we can change memories simply by presenting the right information at the right time. Good adverts or teachers can exert as much power as a drug.

Kindt thinks that many of the knee-jerk responses ignore the fact that our everyday lives are full of things that can alter our memories. “Some people are very afraid of the idea that if you take a pill, it could influence your memory,” she says. “But psychological processes, such as repetition, interference and even sleep, could also influence the neurobiology of memory, more so than a pill.”

Indeed, scientists are expressly trying to harness these techniques. They realise that a distraction can rewrite fears just as effectively as chemical intervention. And what better distraction than Tetris? Emily Holmes, from the University of Oxford, asked people to play the classic video game after seeing a grisly film featuring surgery and accidents. She found that while these volunteers remembered just as many details of the film as those who did not play Tetris, a week later they had fewer flashbacks and were less affected emotionally by what they had seen.

Holmes thinks that the game hogs the brain’s processing power. As a result, during the time window when memories would have been firmly etched, the volunteer’s visual and spatial faculties were not available to record long-lasting imagery. Instead, they were busy pushing geometric blocks around a computer screen. Tetris acts as a mental vaccine that protects against the creation of strong fear memories and removes their emotional burden.

Such experiments can ease the load of those suffering from PTSD or acute phobias. These people form a significant part of the population. PTSD and depression are estimated to affect nearly 20 per cent of Americans who have returned from service in Iraq and Afghanistan. The US National Institute for Mental Health believes that around 19 per cent of American adults suffer from a significant phobia. Memory manipulation could get rid of painful associations that certain objects or recollections carry.

The recent evidence from Elizabeth Phelps at New York University suggests another way to reshape memories. After training volunteers to be wary of a coloured square by pairing its appearance with a mild electric shock, she found that she could remove their anxiousness by deliberately triggering their fearful memory and rewriting it. She did this by exposing them to the square without the shock. Remarkably, the effect lasted for at least a year. An existing treatment, called Eye Movement Desensitisation and Reprocessing (EMDR), works along similar lines: patients keep a traumatic memory in mind while moving their eyes about. This is thought to interfere with the reconsolidation process.

But perhaps the most effective way of erasing memories was discovered a few years ago by Todd Sacktor, from the SUNY Downstate Medical Centre in New York. He believes that memories are strengthened by a protein called PKMzeta. This effectively acts as glue, turning up at specific synapses when we learn new things and doubling the strength of their connections.

Sacktor says that this discovery has prompted a “revolutionary change in how neuroscientists have thought about memory”. It suggests that our memory is a dynamic machine that needs the constant activity of PKMzeta to stand the test of time. With this power supply memories can last for years; without it they are lost. It is likely that the process of reconsolidation involves breaking down and remaking PKMzeta at specific synapses, and drugs such as propanolol work by obstructing this process.

In order to test his theory, Sacktor trained rats to avoid the taste of saccharin, an artificial sweetener. He then removed this aversion with a single injection of ZIP, a chemical that interferes with PKMzeta. The dose does not stop rats from laying down new memories, but it does erase existing ones, even if they are very strong and relatively recent. Even more dramatically, the process seems to be irreversible and universal. Sacktor says: “It applies to all parts of the brain that store different types of memory, like the amydgala that stores fear memories, the hippocampus that stores place memories, or motor memories in the motor strip. They’re all using PKMzeta.”

The discovery of this protein has raised yet more ethical concerns, especially about the potent and far-reaching effects of blocking it with ZIP. Such queries remain the field’s greatest dilemma: does the excitement of new discoveries outweigh concerns about their application? “I was initially worried, too,” says Sacktor, “but [applications] wouldn’t happen for a long time in the future. And it’s not just about the dystopian fantasies of making zombies or toying with people’s memories. I think the actual good is going to far outweigh the potential for bad.”

The little round pill that wipes away all our memories remains firm fiction. Instead, scientists strive to blunt the most painful edges of our memories while leaving the substance intact. Until we understand how memory works, sufferers of acute fear will remain paralysed. “We are our memories; our mental states are based upon everything we’ve learnt,” Sacktor says. “You can’t hope to treat addiction or post-traumatic stress disorder in a fundamental way until you really know how these processes work.” With so much to gain from memory research, it would be shameful to let fears of misuse cloud our judgment. As Nietzsche put it: “The only thing we have to fear is fear itself.”

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