Towards altering our concept of fear and addiction
Writer: Alexandra Gilbert
Editor: Rachel Rubinsohn
Artist: Will Ning
The red pill that bestows the terrifying truths of reality or the blue pill that provides stability and safety; which would you pick?
During the Matrix movies, the main character, Neo, must choose between two worlds, each pill altering his memory either in favour of a virtual reality, or a devastatingly authentic one. Here, the writers of the movies raised a tantalising question: what if we could erase, or edit, our memories?
Other than blocking out cringey high school moments, there are plenty of clinical reasons why we might want to edit our memories. Forgetting the craving cues characteristic of drug addictions and painful pasts in post-traumatic stress disorder (PTSD) are a top priority in the field, along with dabbles in memory enhancement for educational purposes.
Despite the attractive (or unattractive) sentiment, the specificity of memory alteration seen in sci-fi scenarios is not so easily reproduced. Emotional memory is normally the target for PTSD and addictive disorders. Let’s consider what this entails.
Emotional memory starts with emotional arousal in the amygdala and hippocampus, with some involvement from the basal ganglia and hypothalamus. It’s complicated. Next, our emotional memory is utilised in decision-making circuits of the prefrontal cortex, and also affects motor and reflexive action. And so, the emotional memory sinks its teeth into our behaviour.
To further complicate matters, the only success that scientists have had with directly inserting, deleting and replacing memories, involved invasive electrical stimulation in mice.
Complete and targeted memory editing has eluded us, due to its complexity, and our lack of complete understanding of standard memory-forming mechanisms. But that doesn’t stop science from giving this challenge a good shot.
Non-invasive techniques that aim to adjust unconscious learning patterns and behaviours have been around since Pavlov and his seminal 1890s classical conditioning experiments. Our very own Clinical Psychopharmacology Unit at UCL published an article in Translational Psychiatry (2015), on breaking the habits of alcoholics by relearning the motivational mechanisms behind the hunt for the next bottle.
What’s important are the cues associated with drinking or fearful recollection of traumas. During a process called “reconsolidation”, existing memories are reinforced. For example, the more time you spend drinking in the local pub, the more you associate the pub with drinking. The next time you visit the bar, you’ll be more likely to indulge in a pint. But, by repeatedly exposing someone to the same stimulus, just without the alcohol consumption, new memories can be formed that don’t induce drinking oneself into a stupor.
Other techniques involve “updating” memories using a combination of stress hormone manipulation and drug administration. By using these agents at particular segments during reconsolidation or relearning, one can disrupt or augment the target memory.
Soon, clinicians will be able to give patients the memory-altering pill they need to alleviate the nightmares and addictions, to a certain extent. Not to mention the incredible uses for memory enhancement using similar approaches. The questions arise: where is the line for editing memories? Who qualifies for these procedures and drugs, and what implications lie ahead of us if we are able to manipulate the very essence of who we are?
The red or the blue pill, authentic or artificial – which would you choose?
References
Cahill E, Wood M, Everitt B, Milton A (2018) The role of prediction error and memory destabilization in extinction of cued-fear within the reconsolidation window. Neuropsychopharmacology 44:1762-1768.
Das RK, Lawn W, & Kamboj SK (2015) Rewriting the valuation and salience of alcohol-related stimuli via memory reconsolidation. Translational psychiatry, 5(9), e645.
Davis M, Myers K, Chhatwal J, Ressler K (2006) Pharmacological treatments that facilitate extinction of fear: Relevance to psychotherapy. NeuroRX 3:82-96.
Phelps E, Hofmann S (2019) Memory editing from science fiction to clinical practice. Nature 572:43-50.
de Sousa A, Cowansage K, Zutshi I, Cardozo L, Yoo E, Leutgeb S, Mayford M (2019) Optogenetic reactivation of memory ensembles in the retrosplenial cortex induces systems consolidation. Proceedings of the National Academy of Sciences 116:8576-8581.
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