Memory editing for mental health – Part 2: Manipulating memories to control our fears
Deep dive by Conor D’Andrade
This is the second part in a series of three articles about memory reconsolidation. You can read part one here.
Even with millions of years of evolution on its side, the human brain can still be duped from time to time. One area that can be particularly affected is in the creation and management of memories which is central to many cases of mental health issues, from post-traumatic stress disorder to substance abuse. In the second of three articles on the subject, Conor D’Andrade further explores memory reconsolidation, and how we can begin to manipulate it for our benefit.
There are two main ways to interrupt the reconsolidation process. The first is to use a pharmacological intervention before the process is complete.
Interrupting reconsolidation with medicines
This theory was first tested in 2000 using a drug called anisomycin which scientists injected into rats while reconsolidation was occurring. Before they did this though, the team first had to train the rats to form a memory that related to a specific stimulus using what’s called ‘classical conditioning’.
If you aren’t aware of classical (AKA Pavlovian) conditioning, it is essentially about forming reflexive reactions to specific things. For example, if someone was to pinch you every time a bell rang, you would begin to fear being pinched every time you heard the bell.
In the case of the rats, all of them were played a sound shortly followed by a small electrical shock. The next day, the sound was played again, and the rats froze as they were expecting a shock to follow – they had been classically conditioned to fear the shock associated with the sound. At this point though, half of the rats were injected with anisomycin and half were injected with a placebo. On the third and final day, the sound was played once more… and those who were injected with the drug didn’t freeze, indicating that the drug had interrupted the reconsolidation process.
Now, a very good question at this point would be ‘how do we know that it was definitely the drug that interfered with the process?’ – and the answer is that it was confirmed in another group of rats.
The experiment remained the same, except on day 2, a third group of rats received a dose of anisomycin 6 hours after presenting the tone. For this group, results were similar to the placebo group on day 3 – when the tone was presented, they froze with fear as they expected the shock to follow. This indicated that the reconsolidation process had already finished when they were injected with anisomycin, so their fear remained like the rats that received a placebo.
So, what exactly is happening in the brain that is stopping the reconsolidation process? The answer is complex, so we will only scratch the surface.
Evidence suggests that anisomycin injections cause significant changes in the release of molecules called neurotransmitters, one in particular being norepinephrine.
To go into all of the roles norepinephrine plays in the body would take far too long, but one process of particular interest in this case is the formation of memories.
Studies have found that, while low doses of norepinephrine can enhance memory, high doses of the molecule can impair it. So, with anisomycin causing such an increase in norepinephrine, we can believe that this is how it prevented the reconsolidation process. Research also suggests that, when the brain releases lower levels of neurotransmitters – which tends to be the case after a period of high neurotransmitter release – the physical changes that occur in neurones can also be inhibited (essentially it prevents neurones that fire together from wiring together).
These effects aren’t just seen with anisomycin. Another class of drugs called beta blockers have also been shown to block the reconsolidation process by reducing reduces levels of norepinephrine.
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Psychologically interrupting reconsolidation
As I mentioned earlier, pharmacological interventions aren’t the only means of interrupting memory reconsolidation. Psychological interventions have also been shown to be effective, without presenting the potential dangers of invasive drugs.
Researchers have found that the most successful psychological intervention for interrupting memory reconsolidation is the use of something called a ‘visuospatial task’. To describe them simply, visuospatial tasks require our brain to make sense of all the information it gathers from our environment and our senses and have us respond correctly. We experience visuospatial tasks pretty much all day, from walking to driving to texting.
In 2018, an experiment was carried out to test how effective a visuospatial task could be at preventing memory reconsolidation. All participants were given the task of watching a video and then having to recall details from it. But in between watching it and recalling it, they experienced one of four different scenarios:
A prediction error and then a visuospatial task (in this case, a complex word search)
A prediction error and then a control task
No prediction error and then a control task
No prediction error and then a complex word search
You may remember from part one that ‘prediction error’ describes the mismatch between an expectation and an experience and is also a way of kickstarting the reconsolidation process. The group of interest in this study then was the top group.
The researchers found that a prediction error followed by a visuospatial task disrupted the reconsolidation process, which reflected in their performance on the free recall task which was the worst of all groups, as you can see below.
The reason for the visuospatial task interrupting the reconsolidation process was because it competes for the cognitive resources needed for memory formation.
A chance to update memories
Now, do you remember what I said at the end of part 1 about being able to edit memories and how that could help people? Well, here’s where that comes into play because psychological interventions don’t only have the means to interrupt the reconsolidation process – they can also target memories and update them with new and useful information.
In 2010, scientists proved that old fear memories in humans could be targeted and updated with new non-fearful information, using so-called ‘extinction treatment’ during the reconsolidation window.
Extinction treatment is a technique used to weaken the association between a conditioned stimulus and an unconditioned stimulus by no longer reinforcing it. For example, like in the earlier experiment, if a sound is paired with a shock, the rat learns that the sound means there will be a shock. So, next time the sound (the conditioned stimulus) is played, the rat is certain the shock (the unconditioned stimulus) will follow. If we present the sound and no longer present the shock, eventually the rat stops expecting the shock to follow the sound. This is because we have stopped reinforcing the association between the two stimuli.
The power of extinction treatment was proven in a study of humans which used a similar format as the study with rats. On day 1, all participants were trained to fear a shock when they heard a specific sound. On day 2, two of the groups were played the sound again before receiving extinction treatment either 6 hours or 10 minutes later – the third group were not given a reminder before receiving extinction treatment.
The extinction treatment proved incredibly successful in removing fear in all groups. However – and this is the really interesting part – when attempting to train all participants to fear the sound again, those who had received extinction treatment 10 minutes after hearing the sound for a second time showed no fear at all. That’s because the extinction treatment has been administered during the reconsolidation process.
Mean measure of fear scores before extinction treatment, after extinction treatment, and after attempting to retrain fear. Source: Schiller et al 2010.
Perhaps even more fascinating is that these psychological changes were present in a physical manner too. In research published five years later – which replicated this experiment but also took fMRI scans of the participants brains – the area of the brain that is involved in us feeling fear was not active in the 10-minute group for up to 18 months after the experiment took place. So not only was the fear eliminated at a cellular level, but it had a lasting effect too.
In part three…
Conor D’Andrade ties together everything we’ve learnt about reconsolidation and examines how the science of editing memories can help treat – and potentially even prevent – mental health issues.
