Brain stimulation and spatial memory

There have been media reports recently about how electrically stimulating the brain can improve memory.

More specifically, a small study, that should be interpreted with caution found that, in patients being prepared for surgery to counter epilepsy, electrical stimulation of the entorhinal cortex improved spatial memory. This improvement was measured by having the patients drive a virtual taxi on a computer and evaluating how well they remembered different routes with and without stimulation.

Mo Costandi analyses the study in The Guardian and explains:

"Since this effect occurs during the learning phase, it seems that electrical stimulation of the entorhinal region facilitates encoding of the spatial memories, and the researchers suggest that it does so by resetting low frequency theta oscillations, which optimizes memory formation by synchronizing electrical activity of the cells needed."

I commented on one report as follows:

This is interesting, but is there a connection between the stimulation of the applied electrical signals and simply exercising the brain through using the memory?

As I approach fifty, I've thought my memory was getting worse. However, since reading recently of people who can remember every day of their lives I decided to remember every day going forward. A couple of months in, this seems to be working and seems to be having a wider impact. I'm blogging about the experience here:
http://lembransation.blogspot.com/2012/01/how-it-began.html

Although something that helps people with medical problems is to be welcomed, I wonder whether this electrical stimulation of the memory is like those machines that twitch your muscles to tone you up so you don't actually have to do exercise.

After all, real taxi drivers have been found to undergo changes to their brains as they memorise routes, as the BBC reported in December 2011.

Reference: Suthana, N., et al. (2012). Memory Enhancement and Deep-Brain Stimulation of the Entorhinal Area. N. Engl. J. Med. 366: 502-10.

A pill to forget

There is a fascinating article on Wired.com about how memory is thought to work - and how it may be possible to chemically remove troublesome memories, such as those causing Post Traumatic Stress Disorder.

http://www.wired.com/magazine/2012/02/ff_forgettingpill/all/1

On formation of memory it states:

Every memory begins as a changed set of connections among cells in the brain. If you happen to remember this moment—the content of this sentence—it’s because a network of neurons has been altered, woven more tightly together within a vast electrical fabric. This linkage is literal: For a memory to exist, these scattered cells must become more sensitive to the activity of the others, so that if one cell fires, the rest of the circuit lights up as well. Scientists refer to this process as long-term potentiation, and it involves an intricate cascade of gene activations and protein synthesis that makes it easier for these neurons to pass along their electrical excitement. Sometimes this requires the addition of new receptors at the dendritic end of a neuron, or an increase in the release of the chemical neurotransmitters that nerve cells use to communicate. Neurons will actually sprout new ion channels along their length, allowing them to generate more voltage. Collectively this creation of long-term potentiation is called the consolidation phase, when the circuit of cells representing a memory is first linked together. Regardless of the molecular details, it’s clear that even minor memories require major work. The past has to be wired into your hardware.

I posted the following comment.

Since reading a couple of months ago about people who can remember every day of their lives back to early childhood, I've been conducting an experiment remembering every day going forward and reclaiming as many memories for specific dates in the past. It is working surprisingly well and having a wider impact on the effectiveness of my memory.

My experience chimes with the reconsolidation theory explained in this article. I have memory tags consisting of trigger images pinned to a mental calendar. These become embedded through a process of remembering the images for the past ten days or so and then for the same day of the week for dates beyond this window and, if time allows, the same day in past months and the same date in previous years (where I have to fish around for clues as I didn't record memory tags at the time).

I'm blogging about this experiment here: http://lembransation.blogspot.com/

This has convinced me of the capacity of the mind: this process seems to be getting easier with practice, not harder as my memories accumulate.

It has also shown me that the memories I retain are to a large extent a matter of choice: I remember who I was with, what I did, conversations, the weather. But not what I ate or what was in the news, because in general I don't use those factors in my memory tags - though occassionally I do and perhaps I will be able to add them to the richness of the memory as I become more skilled.

It has also shown me that it is as easy to record false memories, which I think I am avoiding because in reinforcing the memory tags (perhaps I should now say "reconsolidating") I don't cement in something as fact unless I am sure; sometimes it is tempting to just say, "It probably was on that Thursday" but I resist.

One other thought is that I find to an extent some validity in the memory as video view because from the memory tags I have been able to identify the details and timing of events that I had not made a point of remembering at the time. There is a trivial example on my blog of trying to remember when I had made a cake which explains how this worked:
http://lembransation.blogspot.com/2012/02/baking-cake.html

My idea is to continue this for some months and then, in parallel, try to pin down more for the dates before I began this process - that is where I will encounter painful memories (though, not doubt, I also face some in the future) which invoke a strong physical and mental reaction when I do call them up. I'm not sure I would want to zap them with pills, though.

Remembering perfection

Some months ago I thought, "This is a perfect time. I am very happy."

This was immediately followed by a worry that to think it was a time of perfection was to put it at risk, to tempt fate.

I felt uneasy, that something would go wrong to shatter the happiness. A loved one may die, or become ill while I was far away. Another form of disaster could befall me or my wife.

I realised it was a certainty that the time of perfection would not last: time passes.

My superstitions are long dead. What is in my mind will not make my loved ones more likely to suffer an accident or illness. Even the preachers who claim distant events can be influenced by prayer do not suggest our happiness will be punished by tragedy (unless you are Job).

So best to enjoy the happiness while it lasts.

We had returned to my wife's country and she was overjoyed to be catching up with family and friends and looking to restart her career. I had enough work to keep me busy, but also had time to exercise in the agreeable climate, shedding the pounds that had made me a stranger to myself. We were back in our home, our bills were low and debts built up under less favourable circumstances were rapidly being cleared.

In our relationship, we seemed to be on the same side, us against the world, challenges making us stronger, not driving us apart. It was not always so.

This was before I began this process of remembering, meaning I don't have the luxury of being able to scan back through every day of this happiness. I wish I did.

I do clearly remember the morning I awoke to it and dismissed the fear that noticing would jinx it.

It ended sooner than I hoped. My wife's plans did not go as she wanted and she suddenly announced she wanted us to return immediately to my country. She could not articulate a clear purpose to justify the financial consequencies and we argued about the sense of it, but in the end we returned.

Three months later, we are settled, but the harmony has not yet arrived. It is a trick of memory that moods bring back memories associated with the same mood. When relationships breakdown, partners catalogue events both recent and long past, a chain of hurt that hides the links of love and happiness.

Which is why it is important to me to be able to remember there was a time not so long ago when things were perfect. It is a chain of those events I wish to see.

Sweet memories

The biochemistry of memory involves teasing out the most intricate secrets at a molecular level.

In news just in, researchers at Caltech have apparently found evidence of the important role played on memory by a sugar with the name O-GlcNAc. In an experiment mice were investigated to see how well they could remember that a tone was associated with an "unpleasant stimulus".

I need to buy the research paper to find out what they did to the poor mice - usually an electric shock in these types of study - but whatever it was the mice were more likely to remember it two hours later if the sugar was prevented from attaching to transcription factor cyclic AMP–response element binding (CREB) protein. The axonal and dendritic growth that takes place in the brain to store memories was enhanced by blocking this process, known as glycosylation.

More succinctly put, the mice were more likely to remember if glycosylation of the CREB transcription protein was blocked.

More simply put, by me, the brain changes that happen when memories are stored were enhanced when this sugar wasn't messing things up.

The mice were judged to remember if they displayed defensive behaviour when hearing the tone, freezing in preparation for whatever that unpleasant stimulus was.

According to the report in Chemical and Engineering News the research "reveals a previously unknown sugar-based mechanism for regulating gene expression, neural development, and memory. It could lead to new ways to enhance memory or to reduce memory loss among patients with diseases such as Alzheimer’s."

Memory is mechanistic and so magic pills may provide benefits, particularly when the brain starts to go wrong. The sugar O-GlcNAc seems to be involved in many cell processes so I imagine that the process of preventing it from attaching to the CREB transcription protein does not rely on removing it from the body, but either providing something else that it is more prone to attach to, or something that will attach to the CREB instead without having an effect.

Pinning memory tags to my mental calendar results in me remembering better presumably because it too enhances axonal and dendritic growth in my brain. Whether my generally improving memory is due to this process blocking glycosylation of the CREB is another question. There are undoubtedly many other mechanisms at work of which I currently know nothing, but am now interested to learn about.

New improved memory tag

It is now exactly two months since I began this process of remembering every day of my life. So far, so good.

I can recall what I was did on every one of the days of this period, who I was with, where we went, the weather.

This information comes to mind from thinking of the date on my mental calendar. I see the image I have pinned there as a memory tag and the rest of the day flows from that.

Going back beyond two months and there is the familiar fog.

I might be able to remember where I was. I can only remember what I did exactly if the date is significant. More often the best I get is a generalised sense of mashed experiences; many days merge into any day for that time and place.

I much prefer remembering.

A lot has happened in the past two months, even if much of it is mundane. The routine makes it a challenge to choose a memory tag that captures each day's uniqueness.

Sometimes I've found the memory tags first selected need some improvement. For Wednesday 8 February, I chose to store away a conversation with my parents about the medication I needed for my wife. It was symbolic of how they have been there for me in things big and small and how I will miss them when they are gone, if I don't go first.

Then I found just a week later I couldn't for the life of me remember whether I had been in the office that day or worked from home. The following days also had more quirky memory tags and I had no strong sense of where I had spent them.

It took a  little while to remember one incident that brought the work aspect into sharp focus. It came back to me that I was in the office on the Wednesday because a co-worker had left a message, but was not in herself. I wrote a reply on her message and we discussed it on Friday, because I didn't go in on Thursday.

Adding the image of writing the reply to my internal calendar for 8 February is enough to sort out my movements for those three days.

For a moment I thought it didn't matter, to let it go. Let the fog descend again.

But I have chosen clarity. I believe my mind has the capacity to remember these details. I am going to work on the theory that I will be able to remember more details of each day as I continue this experiment, not less.

Sleeping and memory

Around the world headlines are appearing saying things like: "People who have trouble sleeping twice as likely to suffer memory problems in old age".

These arise from a press release issued by the American Academy of Neurology, which itself has the title: "Trouble sleeping? It may affect your memory later on".

You could be forgiven for believing that scientists had found that if you have trouble sleeping this will affect your memory. But that is not what the study found.

The study looked at the sleep patterns of 100 people (a low number in research terms) aged between 45 and 80. Of these 25% had evidence of amyloid plaques. Whatever these may be, we are told they can appear years before the symptoms of Alzheimer's disease begin.

People who had trouble sleeping were more likely to have amyloid plaque build-up compared to people who didn't wake up as much.

The obvious question is what came first? The chicken or the egg?

Does trouble sleeping lead to amyloid plaque build-up and consequent memory problems, or does amyloid plaque build-up cause trouble sleeping?

One of the researchers' definitions of "trouble sleeping" is waking up more than five times per hour. If I was waking up five times per hour, I'd think I had a problem.

The press release quotes a researcher: "The association between disrupted sleep and amyloid plaques is intriguing, but the information from this study can't determine a cause-effect relationship or the direction of this relationship."

So it would have made as much sense to give the press release the heading: "Early stage Alzheimer's disease? This may affect how you sleep".

It's like the difference between: "Trouble sleeping? This may be bad for your back" and "Bad back? This may affect how you sleep".  Either - or both - may be true if people with bad backs have trouble sleeping.

The researchers warn against jumping to the conclusion implied by the press release headline. But people are. A comment on the first article cited above says: "So sleeping pills do more good than harm !"

Perhaps, but as a researcher says: "We need longer-term studies, following individuals' sleep over years, to determine whether disrupted sleep leads to amyloid plaques, or whether brain changes in early Alzheimer's disease lead to changes in sleep."

So sleeping pills may treat a symptom, not a cause, of early Alzheimer's.

All very "intriguing" as the researcher says.

My conclusion is I need to look beyond the headlines of science reports and rest easy.

Panic over?

As the train pulled into the station and I gathered my things together, I started to reach for the piece of paper where I had noted the details of the next part of my journey.

Then I realised I could remember them: the number of the bus I needed and the street where to find the bus stop. The kind of details I was used to forgetting as soon as I knew them.

That's exactly what happened at my wife's church on Sunday, where a family introduced themselves to us. At the end of the conversation I asked them their names again. They are with me still. So too are the names of the couple we met on 18 December, the second day of this experiment. Details I decide to remember are staying with me.

The discipline of remembering every day of the last two months has either switched something on in my brain or simply convinced me at a fundamental level that I can remember if I want to.

This is a new ability - or at least a vanished one recovered - and it feels fragile, not to be taken for granted or fully trusted yet. Too often I've felt the panic of a lost memory. But it feels exciting, like a new relationship.