Neurons to Behaviors #2: Memory and Spaced Repetition

by | Apr 28, 2020 | General Information, Neuroscience | 6 comments



There is something fundamentally mischievous about the human memory. We might remember an incident from when we were ten years old, perhaps of a rainy day when our mom let us buy butterscotch ice cream at the kiosk next to school. But most of us don’t remember what we wore three days ago.

You could argue that a critical component of memory is attention and emotion. That ice cream from ten years ago is memorable because it was an anomaly, or because it made our day. The shirt from three days ago did not. But in that case, why is it that I forgot the important lectures from college, where I definitely paid close attention? Or what I did on my eleventh birthday, which I’m sure was joyful and memorable? This isn’t to say none of you do. I’ve met people who had super-heroic memory, being able to list the names of all their teachers from school. Yet, what is this fiendish mechanism that lets us learn new information limitlessly, but acts so poorly in maintaining that and retrieving it when there’s a need at hand?

The concept of memory is obviously too huge to cover in a mere article. So in this piece my focus is on explaining a particular phenomenon known as Long Term Potentiation (LTP) that is closely related to memory and talk about a few scientifically proven techniques to improve yours. This is part of a series where I give my best shot at connecting the behaviors of the neurons to the behaviors that make it into the world. If you’re interested in learning what it means to learn, you should read the first article.



Enter the hippocampus

In a way, learning and memory share a lot of the underlying electrochemical mechanisms. In part I, we saw that learning a new piece of information meant that in a certain part of our brain, thousands of neurons are firing neurotransmitters and action potentials between each other. Memory is pretty much the second step to that process of learning. It is the concept that helps us retain what we learnt, and hopefully recall when we need it. Memory is more explicit though, but no different than learning because the same process of neuronal firing takes place when you recall something.

That simplistic view soon gets complicated when we realize we have 100 billion neurons and 100 trillion synapses. Numbers too big for our own brain to comprehend, ironically. But, keeping that aside for a moment, memory is known to be associated with certain parts of the brain more than others.

“Explicit memory depends on the integrity of temporal lobe and diencephalic structures such as the hippocampus, subiculum, and entorhinal cortex. Implicit memory includes simple associative forms of memory, such as classical conditioning, and nonassociative forms, such as habituation, and relies on the integrity of the cerebellum and basal ganglia.” – Long-term Potentiation and Memory by M.A. Lynch 


A zoomed in pretty cool picture of the hippocampus. If you’re interested in a full brain dissection though, go nuts with this one


In the history of memory studies, there is a particular one from 1957 that stands out. It stands out because it was an unexpected case study. A serendipity, if I may. It involves Henry Gustav Molaison, a name well-known to anyone in the neuroscience community, who suffered from epilepsy that was caused by a head injury when we was very young. At age 27, he decided to undergo surgery performed by William Scorville and Brenda Miller, a pioneering neurosurgeon and his doctorate student.



Scorville performed what is called a bilateral medial temporal lobe resection, essentially removing parts of Henry’s temporal lobe, hippocampus, and amygdala. However, his epilepsy was not the only thing the surgery took away. What Scorville, or anyone for that matter, did not know back then was the strong relationship between the hippocampus and memory. After the surgery, Henry could remember his name and childhood memories, but the eleven years leading up to his surgery were wiped off from his mind. He also suffered from anterograde amnesia, meaning he couldn’t form any more memories after the surgery, forgetting whatever he learnt in a matter of seconds (a concept popularized in the movie Memento).

This was transformational for neuroscientists and surgeons. Until then, they thought memory occurred throughout a brain, not limited to a particular organ or set of organs. Of course, they didn’t have a way to know since something as unexpected could not have been replicated in a lab experiment. This led to a flurry of future research on the connection between memory and the hippocampus (along with the temporal lobe). The more famous one is the Morris Water Maze experiment conducted by the eponymous Richard Morris in 1984, where he placed mice inside a large pool of powdered non-fat milk and analyzed their spatial integrity as they tried to find the hidden escape platform (hidden since the water is opaque and there are no olfactory clues). It was observed that mice with lesions on their hippocampal areas performed particularly poorly in spatial learning tasks.



Although I’ve been talking a lot about the hippocampus, it’s important to note that there are other parts of the brain involved in memory formation. More specifically, the prefrontal cortex plays an important role in working memory, a limited capacity system that takes care of immediate reasoning and decision-making, and remote long-term memories.

But what does any of this have to do with long-term potentiation? Glad you asked. Let’s understand what LTP means first.



The mystery behind long-term potentiation

“Long-term potentiation (LTP) is a persistent strengthening of synapse based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons. The opposite of LTP is long-term depression, which produces a long-lasting decrease in synaptic strength.” – Wikipedia

Simple enough. You already know, if you had read the part on learning, that increasing the myelin coating around the axon helps transmit information faster. LTP is the other way you can achieve this: by strengthening synaptic connections. The synapse is what connects the axon of one neuron to the dendrite of another. Maybe this will refresh your memory.



Let’s do a fun comparison for a moment. Assume that the earth is your brain, and the 7 billion inhabitants the neurons. It’s no 100 billion, but it certainly isn’t too far off. There are many ways you can make the connection between the people in your brain richer. First, you could have more people (duh). This way, I would have the opportunity to be connected to 100 people as opposed to 99. Second, you can add more connections between people (this is all in the pre-internet era of course) by, say, laying a telephone line that only connects those two. And third, you can strengthen the connection of that line by insulating the copper coil better. This way, those two people can speak to each other faster than two others who didn’t get the insulation.



Long-term potentiation is the third option: it strengthens the synapse between two neurons when a specific pattern of firing happens. A suuuper oversimplification: When a friend of yours take the time to call you frequently, and over time you also tend to respond more readily to that friend compared to the others, and eventually you both form a lasting bond and become BFFs.

This was first proposed as a theoretical idea by the pioneering neuroanatomist Ramon Y Cajal in 1894. He proposed that memory formation does not always require formation of new cells. Rather, it could also leverage the connection between existing cells by strengthening the connection. Later, Donald Hebb built on this idea and said the following in 1949:

“Let us assume that the persistence or repetition of a reverberatory activity (or “trace”) tends to induce lasting cellular changes that add to its stability…. When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased.”

These were profound ideas for their time, since it wasn’t until the later half of the 20th century that we had the tools to verify them. It was only in 1966 that Terje Lomo, then a doctorate student, observed that by externally activating a neuronal path to the dendate granula cells in the hippocampus, there was an increase in efficiency in subsequent transmissions of neurotransmitters between those cells.



There are many ways why an LTP could occur (the number of transmitting or receiving ion channels could increase). And there are also many regions where it could, apart from the hippocampus. One example of an LTP depends on the presence of NMDA receptors, a type of ion channel that lets positively charges ions flow through, as explained in this two minute video. But, coming back to the discussion about LTP and memory, how are they related? Does the presence of LTP always lead to improved memory and retention? Does the absence reduce it? Well…

“Is it reasonable to suggest that LTP is a model for learning and/or memory? There is no doubt that consolidation of memory requires some form of synaptic remodeling, and this fundamental requirement is at the heart of the idea that LTP, which also relies on synaptic remodeling, might replicate the cellular changes that occur during memory formation. […] However, it has to be considered that even when the conscious animal is used in the analysis of LTP (and therefore multiple inputs may be activated), recordings are made from specific populations of cells in response to a specific input from a specific collection of fibers.”

There are many studies to show the correlation, but a strong statement is yet to be made.



Putting theory into practice

Well, we read a lot about the role of the hippocampus and LTP when it comes to memory formation. But, how can we implement these ideas practically, in our day-to-day happenings? There are three famous systems that deserve a mention here: spaced repetition, elaborative encoding, and mnemonics. We’ll dive deeper into one of them here.


Spaced repetition

It is an incredibly simple technique. Trust me.

“[Spaced repetition] essentially says that if you have a question (“What is the fifth letter in this random sequence you learned?”), and you can only study it, say, 5 times, then your memory of the answer (‘e’) will be strongest if you spread your 5 tries out over a long period of time – days, weeks, and months. One of the worst things you can do is blow your 5 tries within a day or two. You can think of the ‘forgetting curve’ as being like a chart of a radioactive half-life: each review bumps your memory up in strength 50% of the chart, say, but review doesn’t do much in the early days because the memory simply hasn’t decayed much!” – Gwern Branwen

Like all great inventions, this too has an interesting story behind it. Back in the late 1880’s, a psychologist named Herman Ebbinghaus became the first to systematically tackle the analysis of memory, and he did this by spending years memorizing lists of nonsensical syllables that he made up. By painfully recording his results on number of times a list was studied, reviewed, and remembered (or forgotten), he was able to create a decay chart for our memory, also known as the forgetting curve.



So yes. While you aced the exam by studying the night before, you most certainly forgot it all after three days. If you had employed spaced repetition for long-term retention, you would have begun the process of studying for the exam maybe two months before, and constantly reviewed the topics as you kept close to forgetting them.

Spaced repetition isn’t just a fancy nam; it is a scientifically proven learning technique. Research has shown a clear improvement in long-term memory formation when the learning happens in a spaced vs massed manner (without rest). And surprisingly, this technique can scale to huge quantities of information. It has been used by contestants on the popular quiz show Jeopardy! to learn the answers to over over 200,000 questions.

It is a powerful tool that is riddled with an unmissable paradox though: how will I know that I need to review a concept if I’m close to forgetting it? On the other hand, wouldn’t I remember the concept that I actually did not forget, which ironically, doesn’t need to be reviewed? Yes. Sadly, that’s another foible of the human memory. But this is where technology augments our cognition.

A plethora of software and apps, including Anki and SuperMemo, are at your disposal if you wish to take your learning to the next level. These apps lets you create a flash card that is sent to you for review at a pre-determined interval. Based on your feedback, whether you remember the information on it or not, it will either be shown again sooner or later. The app I recently began using for spaced repetition is Readwise. Incidentally, Readwise introduced a new Master feature in September 2019 such that you can convert highlights into either a question and answer flash card or a cloze detection card.


cloze deletion in Readwise


Side note: If you plan to end up using Readwise, consider signing up with my invite code so we both get a free month. No pressure though. 🙂

On the other hand, if you like to learn about quantum computing or feel like refreshing your memory of it, Adam Mastuchak and Michael Nielson built this wonderfully innovative website called Quantum Country that uses an embedded spaced repetition technique to enhance your memory.

Out of all the explanations, my favorite one of spaced repetition is to think of memory as a battery that gets charged with new information. But, a battery, just like any in real life, drains with time. So the way to recharge it is to keep reviewing that information until it registers itself in a long-term storage space. Begin recharging your battery soon my friend.



There’s no time like now

It would be a shame if you read a 2,500 word article on how memory works and ways to improve it without beginning the implementation right away, now, wouldn’t it? So glimpse over this article one more time and highlight sentences that pique your interest, or facts that you wish to remember later on. Now, install one of the apps mentioned above or create your own and begin adding cards into it.

Slowly, but surely, you will start seeing the effect.

Memory, as I said in the introduction, is a mischievous little thing. The effort you put in at the beginning with these techniques, counterintuitively, will not show pay-off until you’re into the distant future. You need to be okay with long-term returns over short-term gratifications. Profound understanding over all-night study sessions. The best things in life aren’t free after all. They are obtained with compounding effort.


Images Courtesy: Pexels, Wikipedia, Tutor2u, Exploratorium, Waitbutwhy, Springer, McAuliffe Neur, and Education Corner.