Do you remember, the 21st night of September? Do you remember the lyrics? Or would you want to forget ever hearing this song? (I hope the latter isn’t the case). Well, the science of memories continues to be of great interest and has played major roles in a variety of pop culture, whether through memory enhancing drugs (Limitless) or selected memory removal (Men in Black, Eternal Sunshine of the Spotless Mind). But whilst love may change the minds of pretenders, can science be used to change the minds of patients? One day will it be the norm to erase the memory of a bad date, say or used therapeutically to alter a traumatic experience? But what actually are memories – are they even a single entity? Although I enjoy the creative representation of memories in the Pixar film Inside Out as each being collected in glass balls, memories are just not like that in reality. Now, I’m not a neuroscientist expert, but I am still a scientist and was curious to investigate this further, so from reading a bunch of literature, mainly from this recent review 1, I will attempt to evaluate whether memory editing could become mainstream.
What are memories?
“Memory is the glue that holds our mental life together.” – 2. A strong statement, but it’s true. Memory is the process of retaining, reconstructing and retrieving information and allows us to add meaning to everyday life. But what actually is a memory and how is it stored?
Figure 1: Made a photo representation of the quote
Memories can be split into two categories; declarative (explicit) and implicit. Declarative memory refers to facts and events, people’s names, stuff we actively want to remember, so includes the items you would learn for an exam. Implicit memory is retention independent of conscious recollection and includes perceptual and motor skills 2. Both these divisions can be further split up, but the key point is that different regions of the brain are required for these different types of memory.
(A nice, but intense intro to different types of memories à https://www.youtube.com/watch?v=bSycdIx-C48 )
The making of a memory
Neurons present in these different areas are responsible for memory formation. Memory is the strength of connections and activation of a specific set of neurons that also depends on changes in patterns of gene expression and protein synthesis 3. The more active a memory is, the stronger the connections. Memories get lost over time when these connections weaken. Connections between neurons – the synapses – are thus thought to form the basis of memory and depend on the strength and number of connections made between neurons. Neurogenesis – the production of new neurons – may also play a role in memory 4, but less is known about this at the moment.
Bottom line – different types of memories can be stored in distinct brain regions.
So say we want to alter the memory of an event?
Well, the complication is that a single event can include different forms of memory and thus be encoded in a variety of places and expressed in different ways. E.g the example given in this review 1 is recollection of a car accident. This one event includes episodic memory of when and how the event happened, defensive responses to revisiting the location of the accident and habitual responses to avoid that area, to name just a few. The point is that editing the memory may require the modification of all these areas separately which could be advantageous allowing specificity to memory editing but disadvantageous due to the complications it creates. But before going any more depth into the many problems facing memory editing, what methods could even be used to achieve this?
Well, one idea for targeting specific memories is to do it when they are active as this may enhance the search process and hence specificity of the editing. Also, if you are going to edit a memory, the memory already needs to have formed. Based on what is known about memory formation there are two vulnerable windows where modification could take place…Consolidation and reconsolidation (Figure 2).
Figure 2: Stages of memory formation. Targeting memories is thought to be easier when they are labile. There are therefore two potential stages when memories could be targeted; after memory encoding or after reactivation of a memory. Targeting after initial encoding may provide a larger time frame over which to carry out a procedure making it a more desirable option. But how would efficacy vary between the different stages?
Consolidation: The initial storage of a memory
Reconsolidation: Memory re-storage after retrieval
The window is thought to be longer during consolidation where the memory is repeatedly reactivated to transform and stabilise the memory. So what methods could work then?
Methods of memory modifying
- Hormonal effect mimics/blockers: Stress hormones appear to enhance memory consolidation. You may agree that it is easier to remember an emotional event than a neutral one. By mimicking or blocking this hormonal effect memory could be strengthened/weakened.
- Exposure therapy: This works because of extinction learning… To learn that a stimulus is now safe the subject is exposed to what was the threatening stimulus with no aversive consequences. i.e the aversion associated with the memory becomes extinct.. But it doesn’t have to disappear, rather the new memory that the stimulus is “safe” competes. Drugs could be applied during this “reprogramming” to bias the competition in favour of the new memory.
- Targeted memory reactivation (TMR): Now **niche reference alert** I distinctly remember watching an episode of “My parents are aliens” as a kid where Josh played an audio recording while he slept to help him remember items for a test. Well, there may be some truth in it as memory consolidation is thought to involve recurrent reactivations, a process that can still occur when we sleep. With the right cue, TMR could become an effective strategy to enhance memory formation. But there is also now evidence that TMR can be used to suppress memories too 5.
- Behavioural tagging – enhancing a memory by “tagging” it to stronger neural pathways.
- Imagery rescripting – this involves getting the subject to change the outcome of a traumatic event so that it is now non-traumatic – the event is “rescripted”.
Okay, so I haven’t gone into too much detail about these methods but that is partly because the mechanistic underpinnings are not fully understood. Moreover, many of the tests conducted so far have been in animal models and so translating them to humans is another major hurdle to face – would these methods even be effective in humans?
Why would we want to do this?
…It would be cool, obviously. But joking aside, there are many valuable clinical applications of memory editing should it become safe, non-invasive and effective. For example, preventing cravings from drugs to high-fat foods, preventing post-traumatic stress disorder and for enhancing education… and for erasing memories after alien encounters of course.
Will it become mainstream?
Mr Incredible asks if Dicker remembers wiping Tony’s mind.
Dicker: Yeah. Nice kid.
Mr Incredible (Bob): Well, you also wiped out the Friday-night date my daughter had with him. In fact, you wiped out my daughter.
Dicker: Oops. Not an exact science, Bob.
This conversation above made me laugh whilst re-watching Incredibles 2 procrastinating between writing this post, but ho hey, it makes a good point. There are many potential hazards and uncertainties with this memory-editing technology even if it becomes effective. Even if we get the results we want, doesn’t mean we understand why or how we made it happen. Case at hand, say the memory went away; is this because the synaptic connections were “destroyed” or is the memory being outcompeted by novel memories. And if the memories are erased, could this be permanent, or would a trace of the memory remain?
I think what I’m trying to say is that yes, with the hype already surrounding its pop culture usage and the current knowledge we have, sure, memory editing could become mainstream. Just when is the key question.
So this was a somewhat vague introduction to memories and how they can be manipulated. But like I said, I am not an expert in this so if anything you read has sparked your curiosity there is much you can read to find out more!
Further Reading
- Phelps, E. A. & Hofmann, S. G. Memory editing from science fiction to clinical practice. Nature 572, 43–50 (2019).
- Kandel, E. R., Dudai, Y. & Mayford, M. R. The molecular and systems biology of memory. Cell (2014). doi:10.1016/j.cell.2014.03.001
- Focus on memory. Nature Neuroscience (2013). doi:10.1038/nn0213-111
- Akers, K. G. et al. Hippocampal neurogenesis regulates forgetting during adulthood and infancy. Science (80-. ). (2014). doi:10.1126/science.1248903
- Simon, K. C. N. S., Gómez, R. L. & Nadel, L. Losing memories during sleep after targeted memory reactivation. Neurobiol. Learn. Mem. (2018). doi:10.1016/j.nlm.2018.03.003
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