An antidote to fear

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10 million people in the UK suffer from some sort of phobia. At the heart of these anxiety-related disorders are aversive memories, which are formed when the brain makes a link between an object, animal, place, or situation and a traumatic event experienced at the same time. Currently, treatment for these phobias involves gradually exposing a patient to the aversive stimulus until the brain no longer associates it with fear, but new research suggests that this may not be the best approach.

Professor Lucas De Oliveira Alvares at the Federal University of Rio Grande do Sul, and Professor Olavo B. Amaral at the Federal University of Rio de Janeiro, have developed a new method of reprogramming murine brain activity to attenuate the effects of traumatic memories. In their breakthrough paper, published in eLife earlier this year, the scientists outlined their new technique, termed ‘deconditioning-update’, describing it as “a promising therapeutic avenue” for human disorders related to aversive memories.

These memories are forged in the process of associative learning, where the brain establishes a connection between two sensory cues that are coupled together – an unconditioned stimulus, which induces an innate response in the animal, and a conditioned stimulus, which does not. In time, the conditioned stimulus can come to trigger the response independently. Aversive memories, in particular, occur when an object or situation becomes associated with a negative stimulus – one which causes fear or pain.

Aversive memories are a human survival mechanism necessary to make it through everyday life without causing ourselves harm. But they can form irrationally when two stimuli become arbitrarily associated, sometimes to quite a powerful degree. This is best exemplified in cases where an associative memory is formed artificially in the process of classical conditioning. Famously, Russian physiologist Ivan Pavlov conditioned the sound of a bell to trigger salivation in his dogs, even when it was no longer accompanied by food. Similar methods were later applied to humans when the psychologist John B. Watson, in his controversial ‘Little Albert’ experiment, conditioned a phobia of furry objects in a small child by presenting them to him with an uncomfortably loud noise.

It is possible to reprogram these pathological memories, and it turns out that evolution has done part of the work for us. Associative memory allows organisms to adapt to changing environments within their lifetime. There is, therefore, little utility in a memory system which cannot be updated and modified. Memories naturally fade in the process of ‘extinction’, where repeated exposure to a conditioned stimulus on its own can kill an association. This is the principle underlying current phobia therapies, where patients are exposed to their aversion until the brain recognises that it is, in fact, harmless. But experiments have now made it clear that extinction is not terminal. Instead, following extinction, associative memories reside dormant in the brain and can re-establish themselves over time, either spontaneously or upon exposure to the conditioned stimulus in a different environment.

In response to this, the team of Brazilian scientists targeted a different mechanism of memory updating known as ‘reconsolidation’. This occurs following the reactivation of a memory, when the brain adopts a plastic state and the memory is made more malleable and receptive to alteration. To apply their new technique, the scientists first classically conditioned a group of rats to associate a sound with an electrical footshock until the sound brought about a fear response on its own. They then attempted to weaken the association. Instead of removing the electrical footshock and inducing extinction, they replaced it with a much weaker one during the reconsolidation period.

The team is optimistic about their results. They not only found reduced fear response in the rats following deconditioning-update but also, perhaps more importantly, that the weakened association was much less prone to the spontaneous recovery and renewal which commonly occur after memory extinction.

The potential of this new method lies its human compatibility. Scientists have, in fact, been attempting to disrupt the reconsolidation of aversive memories for decades. But most treatments involved the administration of toxic chemical substances, unsuitable for use in ourselves. This new approach is completely drug-free and this, along with the long-lasting effects of the therapy, has exciting implications for the treatment of phobias and other memory-related disorders which affect so many people around the world.