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Memorizing stuff via "non-harmful mini-traumas"

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jnikola
jnikola May 25, 2021
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I was thinking about post-traumatic stress disorder (PTSD) and I realized that the PTDS patients don't visualize, feel and re-experience traumatic situations and feelings out of nowhere. They often need a stimulus to be reminded about the specific situation. The stimulus could be a sound, a smell, a situation, or a complex mix of various factors.

What if we could use this mechanism of "stimulated memory come back" to learn and memorize loads of information and have them available when specific stimuli are applied?

How would it work?
For example, on every slide of the human anatomy presentation, there is a different visual or audio signature. It could be even specific ultrasound or another neuro stimulus. The sign provokes the non-harmful mini-stress, which activates the brain in a way similar to PTSD trauma and the slide gets "stuck" in your brain, while the signature gets remembered by your phone/electronic device (inlcuding keywords). The moment when you want to remember what was on the slide, you replay the specific signature via a keyword and the memory comes back like you lived through it just a minute ago!
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Creative contributions

Smelling salts of different kinds

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Miloš Stanković
Miloš Stanković Nov 07, 2022
Going off the title alone, I thought the approach was going to be more analogue. So I thought of this. Smells seem to be the best at eliciting memories so maybe having a service that would send you different unpleasant smells in bottle caps to utilize while learning is the way to go.
Some smelling salts seem to be so strong that they get really strong reactions from people.
There could be enough different unpleasant smells so that you could have unique connections to the things you're trying to memorize. Also, it's way more accessible.
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jnikola
jnikola2 years ago
Hahaha, very cool video and contribution! The guys are funny. But to return to the point, is there any link that proves that "Smells seem to be the best at eliciting memories"? Because if true, this could be a way of memorizing stuff. However, the number of memories that can be elicited by this approach would be limited by the number of different smells (salts or other means). That could bring us to a point in our lives where we should choose which memories to replace with new ones.
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Miloš Stanković
Miloš Stanković2 years ago
J. Nikola There's a lot of evidence for smell being a strong memory activator. Even when you start Googling "why do smells..." it instantly autocompletes to "... trigger memories". I also think if there can be thousands of great, pleasant distinct smells in the form of fragrances, there could possibly be many unpleasant but different ones manufactured.
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Povilas S
Povilas S2 years ago
Miloš Stanković J. Nikola Yes, smells are really great memory triggers, but more when it comes to emotionally charged memories, this is due to the neuroanatomy of smell perception - olfactory bulbs are directly linked to our limbic system, I talked about this extensively in this idea.
Not all memories are equally emotionally charged (your childhood memories vs your studying for an exam in the University) so not sure how this would work for memorizing "dry" information.
The number of shades of smell humans can distinguish is huge. So there's no danger of running out of smells. On the other hand, It might be difficult to produce many different shades of smell. You'd need a specialized device for that.
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Experiment studying under threat

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Darko Savic
Darko Savic Nov 14, 2022
Here's a simple enough science experiment:
  • have a person study a chapter of something, right before taking a test sitting in a chair suspended over cold water. If they pass, don't drop them into the water. If they fail, they drop.
  • repeat with another chapter without the threat of dropping into the cold water and record the difference
  • repeat several times, alternating between threat and no threat of dropping into the cold water
do this enough to build statistics and see if they perform differently with/without the threat
repeat with other people
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Things to do prior to or post some event to better memorize stuff

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jnikola
jnikola Nov 11, 2022
List of things you could do prior to or post any event (training, lesson, course, conversation, etc) to raise the chances of memorizing them better.
Why should it work?
  • Forming memories is assisted by anything that makes a strong impression, whether it's fear, wonder, shame or joy .
  • Thus, anything that boosts forming and processing the impression can be helpful in forming memories.
Things you can do:
  1. Post-event administration of epinephrine and/or corticosterone . Administration of epinephrine into subjects after presentation of emotionally arousing pictures enhances subjects’ memory of the pictures .
  2. Post-event administration of norepinephrine or other noradrenergic agonists into the amygdala
  3. Inducing arousal after the event:
  4. e.g. watching an emotionally arousing pleasant or unpleasant brief video either immediately or after delays of up to 45 min) . For example, college students who watched an arousing video clip after a lecture compared with students who did not watch the clip performed significantly better on a midterm examination 2 wk later .
  5. e.g. holding an arm in ice water has the same effect
Oppositely, to prevent bad memories from forming (e.g. in case of PTSD), you can:
  1. Administer propranolol after the event . It was shown that if subjects got propranolol administered before viewing series of pictures accompained by emotionally arousing story, they didn't memorize stuff as good as those who didn't get propranolol .

Open questions
  • Could these substances be administered by nasal spray as Darko Savic mentioned?
  • Is there any food that raises the proposed substances systematically that could be eaten prior to or post event/training?

[1]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690616/

[2]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690616/#r35

[3]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690616/#r39

[4]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690616/#r112

[5]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690616/#r64

[6]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690616/#r102

[7]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690616/#r108

[8]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690616/#r110

[9]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690616/#r113

[10]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690616/#r62

[11]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690616/#r111

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The memory-forming biomarker test

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jnikola
jnikola Nov 11, 2022
Make a rapid test to see how well is your body prepared to memorize an event you just experienced or will experience shortly after.
Why?
  • Some memories are more important than the others
  • This way we could prepare ourselves by the above-mentioned things to memorize events better
How should it work?
Researchers found that levels of salivary α-amylase assessed shortly after subjects viewed a series of emotional and neutral pictures correlated significantly and selectively with the memory of the emotional pictures on a 1-wk retention test .
We could collect samples of saliva via the kit and send them to the institution that can anlyse them, but what we want is a rapid enzymatic test for one-time use that can give us information if the salivary α-amylase levels are above the threshold determined for good memory forming.
Steps to make it happen
  • determine the threshold of salivary α-amylase levels that often result in a good memory forming
  • create a rapid enzymatic test (similar to COVID-19 tests) for easy assessment of salivary α-amylase levels
  • test them on many types of events and users

[1]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690616/#r117

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Shubhankar Kulkarni
Shubhankar Kulkarni2 years ago
Great! This is also a biotech business idea - making kits. To add to the idea, simply knowing your alpha-amylase levels will tell you whether or not you are capable of making memories at that point. However, events may not occur according to the alpha-amylase levels. Therefore, the kit should also include a set of instructions or harmless tablets that increase the memory retention capacity of the users at that instance. There are foods that improve memory retention. May be such foods or their essential ingredients could be provided with the kit to enhance memory retention, at least temporarily.
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jnikola
jnikola2 years ago
Shubhankar Kulkarni Great idea! Adding harmless tablets or suggesting food that could increase memory retention capacity is a nice addition to the proposed kit.
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jnikola
jnikola2 years ago
UPDATE: There is an alternative method of using a hand-held device that can measure the salivary α-amylase activity with only 5 μL of saliva within 12 min of testing .

[1]https://www.mdpi.com/1424-8220/19/7/1571/htm

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Experiment: epigenetically enhance the efficiency of the memory-forming process

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jnikola
jnikola Nov 11, 2022
Although the idea of memorizing stuff via "non-harmful mini-traumas" sounded pretty straightforward and harsh at the beginning, this contribution is the direction I was planning to go from the beginning but I didn't have a clue how to get here. A recent research paper helped me to sort it out, possibly address or answer some of the safety questions raised by Shubhankar Kulkarni and Povilas S and hopefully drive this idea in a more applicable direction.

Why?
To see if we are able to modify the memory-forming processes (in the example of fear memory) by epigenetic regulation of neurons.
The idea
Since playing with micro dosages of glutamate can be fatal and cannot be targeted to specific neurons, I suggest performing an experiment on rats that would consist of:
  • creating a rat model that has a PRDM2 "switch" (described below) in neurons of the dmPFC that can be used to rapidly degrade PRDM2
  • design and perform an experiment where rats would be conditioned to fear with and without induction with auxin prior or post the conditioning training
  • if it works, find a way to conditionally alter PRDM2 in human dmPFC neurons to make them memorize stuff better

Why should it work?
Research throughout the years has identified brain structures involved in fear memory processing. The most critical for fear conditioning is the amygdala (central amygdala-CeA, basolateral amygdala-BLA). CeA is more involved in expressing the conditioned fear responses, while BLA is the place where associations between conditioned and unconditioned stimuli are formed and stored. The second region of brain involved in fear processing is prefrontal cortex (PFC), which is thought to be closely related to amygdala via dorsomedial prefrontal cortex (dmPFC)-BLA axis.
Regulation of DNA without changing the sequence (epigenetic regulation) is considered to be involved in mechanisms of experiencing and processing stressful event and is thought to be a ke ymechanism that alters transcription and translation in an experience-dependent manner.
PRDM2 (an enzyme that modulates histones - DNA organising structures) is found to be selectively expressed in neurons of the dmPFC and reduced in patients with increased stress responses (alcohol dependencies). In other words, when PRDM" is reduced, the stress-induced relaps to alcohol seeking appears.
Downregulation of PRDM2 in the dmPFC neurons enhances the expression of fear memory by specifically modulating fear memory consolidation (stabilisation of fear memory trace, Figure 1) via dmPFC-BLA axis.
Figure 1. Memory-making process
Prdm2 knock-down (KD) in neurons that project from the dmPFC to the BLA (dmPFC-BLA) altered downstream genes involved in synapse organization and regulation of membrane potential and genes from ephrin, neuroligin, and neurexin families, as well as SNARE associated genes (neurotransmission and memory formation). This information may trigger some ideas.
The PRDM2 "switch"
Scientists have developed and successfully tested novel system for genetic manipulation of protein levels . That means that if you introduce auxin-inducible degron tag and a protein of your choice (in this case PRDM2) into neurons of the dmPFC, you can rapidly degrade the desired protein by exposing cells to auxin. When auxin is removed, protein gets transcribed.
Modulating memory-forming processes with chemicals
It was shown that posttraining administration of epinephrine as well as corticosterone enhances memory for many kinds of training experiences .

[1]Barchiesi, R., Chanthongdee, K., Petrella, M. et al. An epigenetic mechanism for over-consolidation of fear memories. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01758-6

[2]https://en.wikipedia.org/wiki/Memory_consolidation

[3]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690616/

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Povilas S
Povilas S2 years ago
Animal experiments are a non-ethical way of doing science and should arguably be banned.
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jnikola
jnikola2 years ago
Povilas S In 10 to 15 years, I'll completely agree with you. We had a great session that discussed the alternatives of animal models in scientific research. You can check it out and, if you have some ideas, contribute. However, as Manel Lladó Santaeularia mentioned in his contribution, there are currently no alternatives to animal models in preclinical or clinical studies that deliver adequate information. As a person working in science and developing in silico models for various diseases, I hope to be the one contributing soon with some extraordinary breakthroughs in the field of non-animal models. Until then, let's keep this session free of our opinions, and let's build a solid experimental design.
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Povilas S
Povilas S2 years ago
J. Nikola Having no alternatives is not an excuse for doing it. Killing/torturing many animals in hope of potentially healing (or otherwise benefiting) some humans don't seem right to me. It's called speciesism. Morality should be valued above progress. Progress would be even quicker if we kidnapped some humans and performed experiments on them against their will because we have "no better alternatives". Just because animal experimentation is legal it doesn't make it moral. Writing "opinions" is a way of spreading awareness. We also had a session about freedom of speech.
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General comments

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Povilas S
Povilas S2 years ago
The idea is interesting and seems feasible in principle, but I'm concerned about the safety. I agree with Shubhankar Kulkarni that it could cause problems. The functioning of the brain is not well understood and performing experimental psychological conditioning through negative stimuli might lead to unpredicted and unwanted consequences.
If a certain negative stimulus evokes certain information, the reverse effect is likely - that information will be associated in your brain with a negative stimulus and hence unconscious resistance to it might arise, meaning you'd be demotivated to learn or naturally remember something similar (and you might not even be aware why).
A net of associations in the mind is very complex, introducing a negative association in one place might affect the links on the other side of the net. How this will affect the whole system is too difficult to predict, but I have a feeling that it might cause subconscious tension resulting in anxiety or other problems.
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jnikola
jnikola2 years ago
Povilas S I understand that the idea carries a giant safety sign with it. What I would first try would be simple mini-traumas that are not primarily considered negative. A bit louder transition of the slides, the sound of darts hitting the board or turning lights off and on again could serve the purpose to see if things learned during that mini-traumatic event elicit better memorizing.
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Shubhankar Kulkarni
Shubhankar Kulkarni4 years ago
There might be a limit to how much a person can remember even during/ after stress. Also, it may be acute. If we use it for a longer duration (during an entire presentation) or frequently (every day), it might not give the same desired effect. It might even cause additional problems due to the force-feeding of memory. We may have to choose what is more important and then "engrave" only that much into the memory.
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Darko Savic
Darko Savic4 years ago
Could the right cocktail of neurotransmitters be micro-administered alongside every important piece of information you consume? Maybe in the form of a drop, a nasal spray, or something along these lines. If something scares us to death we never forget it. We probably never forget anything that elicits extreme feelings.
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Darko Savic
Darko Savic4 years ago
This scene immediately comes to mind

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