The eyes don't lie

Think back to the last time you used your car, or your bike, to get somewhere. When you reached your destination, what color was the car or the bike parked nearest to yours? Can you remember? Chances are, unless you opened your car door too fast and dinged the one next to you, you probably can’t remember. Now what if I was to tell you that while you can’t consciously recall this information, your brain might still know it? What if there was a way to get at this information? A recent study in the journal Neuron suggests there is a way: by reading your mind through your eyes.

The researchers made participants study three different scenes (for example, a park, a lake, a kitchen) each superimposed with a different face. After a short break, the participants had to do a test. They would be presented with one of the three scenes from the study phase, and after a delay, all three faces seen in the study phase were superimposed on the test scene. All the participants had to do was identify which of the three faces was the one that initially corresponded with the test scene. During the test, two parameters were evaluated: the first one was whether the participant correctly identified which face corresponded with the test scene, and the second parameter was where the participant was looking on the screen, and how much time he or she spent looking at each of the three faces. This was done through a technique called eye-tracking, where a camera records the position of your eye-gaze.

Here is an example of the task

What the researchers found is that the participant’s eyes spent significantly more time viewing the correct matching face (the “right answer”), even when the participant selected an incorrect face as the answer. So what this means is that even when the participants couldn’t consciously remember which of the three faces was the right one, their eyes lingered the longest on the correct face.

In addition to the eye-tracking study, the researchers were looking at brain signals from the participants and determined that the hippocampus, a brain region we already knew was involved in conscious memory retrieval, was also supporting memory even when the participants were making incorrect responses. In a way, this means that your hippocampus supports the expression of memories through your eye-movements, even when you’re not consciously remembering correctly.

The relevance of this study lies in the fact that in some circumstances, the movements of your eyes is a more truthful and reliable account of memories than your verbal accounts. I’m sure you can imagine instances when this could be helpful: for example, to study the memory processes of non-verbal beings, such as babies or chimpanzees (who doesn’t want to know what a chimpanzee is thinking?). However, eye-tracking could also be used to get information from someone who is attempting to withhold it (surely, a more acceptable alternative to waterboarding). So next time you have something to hide, invest in a good pair of sunglasses…

This guy wants to know what you're thinking.

Reference: The eyes have it: hippocampal activity predicts expression of memory in eye movements. (2009) Hannula DE, Ranganath C. Neuron 63:592-599.

Cell phones: curing brain diseases since 2010

If you are like most people, and in particular like everyone I take transit with on a daily basis, you probably spend a fair amount of time talking on your cell phone. If that’s the case, you’ll probably be happy to learn that in 2007, the World Health Organization declared that cell phones are A-ok. Nothing to worry about health wise. Not at all like sticking your head in a microwave. But you’ll be even happier to learn that in 2010 (fresh off the press!), a study published in the Journal of Alzheimer’s Disease suggests that not only is using your cell phone harmless, it might actually be good for you.

The researchers looked at the effect of exposing mice to high frequency electromagnetic fields (similar to the ones you are exposed to when chatting on your cell phone) for a long period of time (2 hours a day for 8 months). They used both normal mice and a mouse model of Alzheimer’s disease. An Alzheimer’s mouse is a transgenic mouse that has a gene that causes some of the manifestations of Alzheimer’s disease in humans.

At the start of the study, before the exposure to the electromagnetic fields, the researchers tested the mice on memory tasks, and as expected, the Alzheimer’s mice were clearly impaired compared with the normal mice. After two months of exposure, no change was observed in either type of mouse. However, after 8 months of exposure to the cell phone-like electromagnetic fields, the Alzheimer’s mice did significantly better on memory tests compared with Alzheimer’s mice who didn’t receive the treatment. Normal, non-Alzheimer’s mice also showed cognitive benefits due to the electromagnetic fields compared with normal mice that didn’t get the treatment.

Time to get Grandma a cell phone? Not so fast.

You may have seen this story in the news. It may have sounded like we finally found a cure for Alzheimer’s disease, and, as a bonus, it’s non-invasive and has no side effects. You may have started thinking of a business plan that involves sewing cell phones into pillowcases for the elderly. Trust me, I thought of this. However, as per usual in the world of science, it’s probably not that simple.

First, I can tell you this: mice skulls are thin, weak, and very easy to cut through with just a regular pair of tiny scissors (how sad is it that I know this from experience?). The skull of a mouse is very different from that of a human, and this means that while the electromagnetic field might penetrate well into mice brains, this may not happen in humans.

Second, the mouse model of Alzheimer’s disease, while widely used and our best tool for these types of studies, is flawed. So extrapolating the results to human Alzheimer’s disease is definitely premature.

Third, if you read the article carefully (I did it for you, so no worries), you’ll find that exposing the older mice to electromagnetic fields has one interesting side effect: an increase in body temperature. It then becomes difficult to tell if the memory enhancement observed is due to the temperature change or the electromagnetic fields. However, this is not necessarily a bad thing. I, for one, would much prefer to prevent cognitive decline by a daily regimen of quiet hot baths then by talking on the phone (though when I was a teenager, my mom would have guessed otherwise).

Finally, there was another sneaky side effect to the exposure, one that was seen only in younger mice: a decrease in three brain compounds involved in battling oxidative stress, including a very important antioxidant. The authors go over this finding somewhat quickly, and suggest that this can be interpreted as a good thing. Unfortunately, I happen to have studied this particular antioxidant quite a bit and I am of the opinion that the finding can also be interpreted as a very bad thing.

Overall, I don’t want to sound like a complete downer. This study was well conducted, showcases very interesting findings, and certainly gives us hope that maybe something can be done for Alzheimer’s disease. But I won’t be sowing a cell phone in my pillow just yet.


Reference: Electromagnetic field treatment protects against and reverses cognitive impairment in Alzheimer’s disease mice. (2010) Arendash GW, Sanchez-Ramos J, Mori T, Mamcarz M, Lin Z, Runfeldt M, Wang L, Zhang G, Sava V, Tan J, Cao C. Journal of Alzheimer’s Disease 19:191-210.

A memorable amnesiac

When little Henry Molaison was 7 years old, he fell off his bicycle. Little did he know that this event was possibly the first link in a chain of events that eventually made him the most famous patient in the history of neuroscience.

Sometime after his bicycle accident, Henry started having seizures. At first they were just little seizures. Then, when he was 16, he had his first major seizure, and it all went downhill from there. Unable to hold a job and not responding to the anticonvulsant drugs that were available, Henry and his family considered a brain operation. His surgeon, Dr. Scoville, wanted to try a new experimental type of surgery, and Henry went for it. So in 1953, when Henry was just 27 years old, he got both his medial temporal lobes removed (kind of like a lobotomy, but instead of removing the front of the brain, they removed part of the sides, just about at the level of your ears).

The operation was extremely successful: the seizures stopped! Unfortunately, this happy outcome was overshadowed by a very strange “side effect”: Henry now suffered from severe anterograde amnesia, meaning he could no longer form new memories. He also suffered from retrograde amnesia: he could not remember events from three to four days prior to the operation, and other events from a more distant past. But the anterograde amnesia was the most astonishing. You could have a conversation with Henry, then leave the room for a few minutes, and when you came back, it was as if he had never met you. Can you imagine?

Dr. Scoville called on one of his friends, Dr Penfield (that’s right, Wilder Penfield, from Montréal!) who then sent his graduate student, Brenda Milner, to study Henry. Even after all that had happened to him, Henry remained a friendly guy and was okay with being studied extensively. The knowledge we gained from Henry (known as H.M. until his death to preserve his anonymity) laid the foundations for much of what we know today about memory (which, I agree, isn’t all that much, but still). For example, prior to Henry, it was thought that memories formed all over the brain. Studying him taught us that instead it is the hippocampus, a part of the brain that was removed during his operation, that is crucial in forming memories. Studying Henry also taught us that there are multiple memory systems, a most unexpected discovery. While Henry couldn’t remember what he had for breakfast 10 minutes ago, he could learn a new task, like drawing a star while only looking at his hand in a mirror (do try this at home to understand the challenge it represents). He would get progressively better and faster at it but never remembered doing the task before. This went on until one day he drew the star and exclaimed: “This was much easier than I thought it would be!”. This lead to the notion that there are different types of memory such as declarative (conscious knowledge of facts and events) and procedural (skill-based knowledge).

The reason I’m bringing up Henry today is because this week, one year after his death, neuroscientists at UCSD started slicing up Henry’s brain in extremely thin slices. These slices will be available for scientists all over the world to look at, analyze and study. Even though he’s gone, there is no doubt we still have much to learn from the most famous neuroscience patient.


Reference: The legacy of patient H.M. for neuroscience (2009) Squire, L. R. Neuron 61(1):6-9

Who wants a memory booster?

One of my first posts was about erasing memories. That may be useful if you suffer from post-traumatic stress disorder or if you just sat through the last installment of the Transformers movies, however, I can think of more people who would benefit from memory enhancement rather than memory erasure. One recent publication in Science hints that this may be just around the corner.

First, how do we know what animals remember? One way to test memory in rats is by using object recognition. You present the rat with two identical objects and let the animal explore them for a few minutes. Then you replace one of the objects with a new object, and typically, the rat will spend more time exploring the new object than the old one (presumably because the rat remembers the old one). By testing rat visual memory performance using this simple paradigm, the researchers established that rats were able to retain information about an object for up to 45 minutes, but after 60 minutes the objects were forgotten and treated as new unknowns. The researchers then injected a special protein in a specific part of the rat’s visual cortex, a part of the brain that is important for processing visual information. Following the injection, the rats were tested again for object recognition, and low and behold, the rats were now able to remember object information for longer than 45 minutes. How much longer? 60 minutes? 100 minutes? 1000 minutes? Actually it was 14 months. The rats went from being able to remember an object for 45 minutes to being able to remember it for 14 months.

Now the relevance of this article mainly lies in the identification of the function of a part of the visual cortex. To confirm their findings, the researchers took control rats (that didn’t receive the special drug) and inactivated the brain cells in the section of interest of the visual cortex (ok, they destroyed them). Those rats couldn’t remember objects at all. Interestingly, the researchers also showed that if you inject the special drug, then introduce a new object, and then destroy the brain cells, the rats will still remember the object for a long time, meaning this specific region of the visual cortex is important for making new memories but not for storing those memories. These are all important findings that further our understanding of visual memory.

But 14 months?? Surely this kind of memory enhancement won’t go unnoticed. The researchers claim that “the role of the RGS-14 protein in the enhancement of visual memory makes this protein an important pharmaceutical target for the treatment of (...) memory defects as well as for boosting the memory capacity”. That being said, I don’t think this drug will hit the shelves anytime soon. First, in the article, the researchers have to inject it directly into a specific brain region, and I certainly wouldn’t volunteer for that. Second, the drug affects an important, ubiquitous protein with many functions, and it’ll be a while before we tease out all the potential pitfalls of toying with something like that.

Regardless, with the aging population and the ever-increasing need (or want?) for maximum brain performance, there is a huge market for memory enhancers and the race is on to develop the first one. Now is the time to ask and answer all the ethical questions that surround this issue. If you had access to memory enhancers, would you use them? What if they were really expensive? What if they had detrimental side effects? What if they had detrimental side effects and everyone in school or work used them to enhance their performance relative to people who don’t use them (Tour de France, anyone?)?

Memory enhancers: useful drugs or can of worms?

The object recognition task

Reference: Role of layer 6 of V2 visual cortex in object-recognition memory. Lopez-Aranda, M.F., Lopez-Tellez, J.F., Navarro-Lobato, I., Masmudi-Martin, M., Gutierrez, A., Khan, Z.U. Science 2009 325:87-89.

Had a bad day? Erase your memories!

The reputable scientific journal Science just published an interesting article about memories called “Selective Erasure of a Fear Memory”. I especially like the fact that I understand 100% of the words in the title (unlike another article from the same issue, “Generation of Follicular B Helper T Cells from Foxp3+ T Cells in Gut Peyer's Patches”, where I score a meagre 46%).

How memories are stored in the brain has always been a mystery. It is thought that each memory is stored in the form of a group of brain cells (neurons), but it’s practically impossible to confirm that because those neurons are all over the place. We do know, however, that a brain region called the lateral amygdala (LA) is where fear memories are stored. Say you’re just a kid and your older sibling decides to make you watch Poltergeist (am I the only one who went through this?). During the really scary parts of the movie, your neurons in the LA make a ton of this protein called CREB (yet another acronym, it stands for cyclic adenosine monophosphate response element binding protein). That’s the tell-tale sign the researchers used to try to identify and then destroy the neurons responsible for fear memories.

They used an experiment called fear training (sounds like torture? Just think about all the people who willingly volunteered to be on “Fear Factor”). They put a mouse in a special cage, and then they play a tone. Right after the tone, the mouse gets a little shock on its feet. The mouse eventually catches on, and freezes when the tone is played (freezing behavior is how we know the mouse is scared). The really clever part of this experiment is that the researchers managed to engineer in the mouse a genetic switch that would selectively kill the neurons that made a lot of CREB (the ones presumably responsible for the fear memory). So after training the mouse to be scared of the tone, they flipped the switched on, the CREB-making neurons died, and voilà! The mouse forgot its fear of the tone and no longer freezes.

So, ok, researchers fried part of this mouse’s brain, and the mouse won’t freeze anymore. Sure, but will the mouse do anything anymore? I don’t know about you, but I’m picturing the mouse in a post-lobotomy state, drooling a little, unmotivated to do anything. Apparently not so. The researchers did a bunch of control experiments to show that the mouse could still run through mazes, store new memories, and even re-learn to be afraid of the tone, if properly trained. They also showed that if you just kill a bunch of random LA neurons (instead of just the ones that make lots of CREB), erasing memories doesn’t work.

So is this relevant? Well, it’s a great contribution to our knowledge of how memories are encoded and stored. A lot of people are excited about this because they see a potential therapy for post-traumatic stress disorder, but to be fair, applications in humans are very, very far down the road, regardless of what the movie “Eternal Sunshine of the Spotless Mind” suggests. If you had a choice, would you erase some bad memories of your past? How did those memories shape the person you are today?