But I digress. You know how, sometimes, right before you fall sleep, you’ll have those weird hallucination-type things, and it’s somewhere in between waking and sleeping and feels surprisingly real? If you don’t know what I’m talking about, then this post may not make any sense to you.

For the rest of you, check out this research where people actually studied those hallucinatory moments right before sleep. By the way, being a participant in this study seems like it was equal parts awesome and annoying.

Who doesn’t like Tetris? (No one.) For this study, in which the participants were almost certainly financially compensated, researchers asked test subjects to play Tetris for two hours every morning for three consecutive days — sign me up! Here is a diagram, because this is the awesome part of the study:

Being woken up 15 seconds after falling asleep.

Then, the researchers told the subjects to take a nap in the afternoon (this study just keeps getting better). Here’s the catch: subjects were woken up either 15, 45, 75, 120 or 180 seconds after falling asleep. The subjects, after mumbling expletives to the scientists, then reported their “mental content” to three judges.

In what may or may not be a surprising result, 10% of the subjects (48 out of 485 people) reported experiencing exact replicas of the sights and sounds of Tetris. This was in contrast to two control groups: one in which the subjects played no games (sad face) and only 1 person in 107 reported Tetris-related hallucinations (ummm…Tetris fanatic much?); in the second group, participants played Tetris after the nap (still a sweet deal), and only 3 out of 112 of those guys pre-dreamed about Tetris (oh, the anticipation!).

So the key takeaway here is simply this: Don’t watch Nightmare on Elm Street films right before taking a nap. Not only because Freddy Krueger will enter your dreams and kill you (duh), but because you might vividly hallucinate about him right before you fall sleep. And no one wants that.

Stay nerdy

Kusse C, Shaffii-LE Bourdiec A, Schrouff J, Matarazzo L, & Maquet P (2012). Experience-dependent induction of hypnagogic images during daytime naps: a combined behavioural and EEG study. Journal of sleep research, 21 (1), 10-20 PMID: 21848802

I'm okay with these kinds of shrooms.

I don’t do shrooms. I don’t advocate for anyone to do shrooms. I know people who have done shrooms, but that’s about it.

I’m talking about mushrooms (aka “magic mushrooms”) containing psychoactive compounds, that people often ingest for recreational purposes.  And so, y’know, over the years as people have regaled me with their shroom-tripping experiences, it’s always something along the lines of “I thought all of the birds were going to attack me!” or “I saw mud people growing out of my living room carpet!”

A) This doesn’t sound fun to me in any way, and B) based on this, I’d assumed that shrooms make people’s brains way too overactive, for them to be experiencing things above and beyond reality.

But, new research says I was wrong about shrooms. Let’s discuss.

Trippy?

From what I previously understood, people would ingest mushrooms, and if they were in a negative state of mind, they’d have a “bad trip.” If they were with friends, with other people tripping, they were more likely to have a “good trip.” Aspects of these trips seemed to include lots of visual and auditory hallucinations: “halos” glowing around light sources, warping colors, maybe some synesthesia.

So I just figured that magic mushrooms must hyper-activate the parts of the brain that perceive color and sound, to the point where people perceive things that aren’t even there.

However, recent research out of the U.K. says that, surprisingly, I’ve got it all backwards. Scientists at the University of Bristol took 30 people and injected them directly with either a saltwater placebo or two milligrams of psilocybin, the psychoactive compound in shrooms. I want to make an aside here: the paper says that “All subjects had previous experience with a hallucinogenic drug but not within 6 wk of the study.” Okay cool, so here’s what I’m imagining:

Within a minute or two, the test subjects started to feel the effects of the psilocybin, and the researchers gave them fMRIs during their trips. Surprisingly to me, and to the scientists, brain activity and blood flow decreased by up to 20% during the influence of the drug, and these decreases were proportional to the reported intensity of the trip! The specific parts of the brain that experienced the suppressed activity and blood flow included the thalamus, the medial prefontal cortex, and the anterior cingulate cortex.

The thought behind this finding is that when people do shrooms, pathways in the brain that would normally restrict cognition are temporarily turned off, allowing people to cognate at higher levels than ever before. Some of these same cognition-restraining pathways are overactive in cases of depression, but I won’t go so far as to suggest shrooms as a treatment for depressive disorders!

In any case, I won’t discourage any research group from trying to find therapeutic value in naturally-occurring psychoactive drugs like psilocybin. In the U.K., at least, mushrooms even rank in as the least harmful drug by some measures:

The brain is already fascinating, and studies like this make it clear that there is a ton of work left to be done in the neuroscience field. The brain is constantly surprising us.

Stay nerdy!

Carhart-Harris RL, Erritzoe D, Williams T, Stone JM, Reed LJ, Colasanti A, Tyacke RJ, Leech R, Malizia AL, Murphy K, Hobden P, Evans J, Feilding A, Wise RG, & Nutt DJ (2012). Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proceedings of the National Academy of Sciences of the United States of America, 109 (6), 2138-43 PMID: 22308440

However, when the subject matter pertains to the devastating mental disorder schizophrenia, it’s important that the makers of the entertainment are conscientious about how the disease is portrayed. There’s already a lot of stigma about schizophrenia in society, including the misguided notion that schizophrenics are running around with uncontrollable, violent alter egos.

Movies like Me, Myself & Irene (promotional photo shown above) don’t do the schizophrenic community any favors. Other movies, like The Soloist, appear to have given much more thought to the complexities of this disease.

In this post, I’ll try to give a simple explanation of what schizophrenia is and how it affects people’s lives, then I’ll do a rundown of movies and books that tried to depict schizophrenia and either failed miserably or made a respectable effort.

In short, no one can tell us why schizophrenia occurs or what exact biology is responsible. We know what schizophrenia looks like: it’s a breakdown of thought and emotion leading to significant social dysfunction. I think it is safe to say that schizophrenia must be characterized by at least two of the following:

1. Hallucinations. (You hear things [most common], see things, smell or taste things that no one else can sense but you.)

2. Delusions. (You may feel like you’re being persecuted in ways that seem bizarre to others; e.g. “I can’t go out in public because the CIA wants me dead and they have people outside my house watching me.”)

3. Disorganized thinking or speech. (Your train of thought is nearly impossible to follow because your speech is incoherent and you switch tracks mid-thought.)

4. Disorganized or catatonic behavior. (Your behaviors are illogical or inappropriate, or you have a flat affect.)

Paintings of cats done by 20th century artist Louis Wain, over a period in which he developed schizophrenia. The effect of the disease on his perception is apparent in his art.

A combination of factors, from genetics to environment to drugs, have been suggested to explain why schizophrenia afflicts people. A genetic link is almost certainly involved, with over 40% of schizophrenics’ identical twins also having the disease (as compared to the 6.5% risk shared by first-degree relatives). Urban living during child- or adulthood has been shown to increase the risk of schizophrenia two-fold. Cannabis use has even been implicated as having a causal role in schizophrenia development. Half of the world’s 24 million schizophrenics use drugs and/or alcohol to excess, but it is difficult to say how much of this behavior can be attributed to coping mechanisms.

So, I never set out to do a study on the depiction of schizophrenia in entertainment media. But I did come to realize that I’ve seen a number of movies and read a novel that all gave unique representations of this disorder…some of those representations were enlightening, and some were cringe-worthy. Below, I will grade works of art and describe what they did right, or, what they did very, very wrong.

1. Me, Myself & Irene. To be fair, I think I’ve only ever enjoyed 20-25% of Jim Carrey’s
movies. Me, Myself & Irene falls into that 75-80% that is almost unwatchable. The synopsis is that Carrey plays the role of a state trooper who is mild-mannered and lovable, until he goes off of his medicine and becomes abusive and violent. The movie that was “pure fun” for Carrey was viewed by the National Alliance for Mental Illness (NAMI) as “irresponsible.” The premise is that Carrey has “advanced delusionary schizophrenia with involuntary narcissistic rage” and is a “schizo” (according to his love interest in the movie, Rene Zellwegger).

What the audience sees is a guy who is normal and likable while on his medication, but when he’s off of it, he poops on his neighbor’s lawn, suckles at a stranger’s breast, and generally has uncontrolled rage. This, unsurprisingly, did little to help the societal stigma that schizophrenics are violent, dangerous people to be feared. In fact, if anything, Carrey’s character in the movie is closer to being a crude, insulting depiction of someone with dissociative identity disorder (aka multiple personality disorder), rather than someone with schizophrenia.

“We’re certainly not out to make fun of anybody,” Carrey said of the film. No, you’re just propagating negative stereotypes about a horrible disease by targeting the very age group with the peak incidence of the disorder, and telling the world that these people are dangerous (and maybe not so much worth helping, since that wouldn’t be as funny). The movie made $150 million worldwide, so a lot of people got the message.

Grade: F-

2. A Beautiful Mind. It was clear to me that this movie was making a more serious, sincere attempt at depicting schizophrenia. The main character, John Nash, was a real person, an actual schizophrenic, and a Nobel laureate at that. The real John Nash was plagued by paranoia, such as the idea that everyone who wore red ties was part of a communist conspiracy against him. He saw himself as having a special purpose, with schemers and enemies trying to persecute him.

Director Ron Howard goes to great lengths to make the viewer understand the all-consuming paranoia that a schizophrenic can feel. And Russell Crowe garners incredible sympathy for schizophrenics with his role. However, it seems like it was only for entertainment purposes that John Nash was seen to vividly hallucinate multiple individuals with constant personalities that stay with him for years and years. Not only that, but the John Nash of the film thinks everyone else sees his hallucination-people and is shocked to find out that others don’t accept reality as he understands it.

A true schizophrenic is much more likely to have auditory hallucinations, which he doesn’t expect others to hear, than to have “imaginary friends” that he believes are fully real. Still, there’s a reason multiple high school teachers made me watch this movie: it takes schizophrenics seriously, and depicts them as people you can respect and even begin to empathize with, even if the movie does take certain creative liberties in the name of entertainment value.

Grade: C+

3. The Soloist. Also based on a true story, The Soloist portrays Nathaniel Ayers, a  prodigy musician who develops schizophrenia and becomes homeless. Ayers inspires numerous newspaper columns (written by Robert Downey, Jr. in the movie), and I won’t ruin the ending for you, but rest assured that you will laugh with, cry over, and root for Jamie Foxx‘s Ayers.

Although the movie only has a Rotten Tomatoes score of 56% (i.e. it’s deemed “rotten” by movie reviewers), this is mostly attributed to a “lack of narrative focus.” The outstanding performance by Foxx is vibrantly complex and, moreover, clinically accurate. Efforts are made throughout the movie to reference Ayers’s childhood and to show the gradual build of his schizophrenic tendencies even from a young age, when he chooses to live in his basement and always be surrounded by his instruments.

Foxx plays a schizophrenic who is both believable and lovable in The Soloist.

One of the most beautiful things about this movie is that before you know anything about Ayers’s illness, you know about his incredible gift for music, and he’s inherently likable because his love of music is so pure. Even once the viewer starts to see the rapid, unexpected shifts in Nathaniel’s moods or the rambling, topic-jumping nature of his monologues, it’s impossible to write him off as just “crazy” — his insights about his home city of Los Angeles are spot-on, and he asks compassionate and worldly questions during his conversations with LA Times columnist Steve Lopez (played by Downey, Jr.). Even Nathaniel’s hallucinations are exclusively auditory (as is most common with schizophrenia) and his voices tell him that others can hear his thoughts (a belief commonly held by schizophrenics).

Clearly, people did their research into the nuances of schizophrenia before setting out to make this film. One could criticize the nature and believability of the friendship between Ayers and Lopez, but I think this movie does much to propagate a view of schizophrenia that makes more room for compassion, kindness, and aid, and leaves little space for fear and ostracism.

Grade: A

This post is getting long, but I just want to make one more plug for a novel that is truly spectacular in that it not only represents a schizophrenic in a factual, dynamic way, but it makes this representation through the eyes of this schizophrenic’s identical, mentally healthy twin brother. In this novel, I Know This Much Is True by Wally Lamb, the narrator goes through life as the privileged twin, preferred by their stepfather and more quick to make friends, but he is also fiercely protective of his less socially adept brother. As his brother develops schizophrenia, a progression which is written with attention to the typical age of onset and early signs of the disease, the healthy twin shoulders increasing amounts of the burden of care for his brother.

This novel does a stellar job of showing the reader that schizophrenia is far from a disease of the individual; schizophrenia affects everyone in a schizophrenic’s life, and even people outside of it. Add to that the fact that the identical twin brother is mentally sound, and thus suffers from the worry of becoming sick and the guilt of not being sick, and you have a book that paints an impressively complete picture of life with this disorder. Selected for Oprah’s Book Club in 1998, I Know This Much Is True is an intensely emotional, comprehensive, and profound read. Don’t be put off by the daunting 928 pages – it’s worth the time, and I definitely give it an A.

In summary, watch whatever you want, read whatever you want, but when it comes to at-risk groups in our society, know what’s real and what’s just for your amusement.

Stay nerdy

Picchioni MM, & Murray RM (2007). Schizophrenia. BMJ (Clinical research ed.), 335 (7610), 91-5 PMID: 17626963

van Os J, & Kapur S (2009). Schizophrenia. Lancet, 374 (9690), 635-45 PMID: 19700006

Large M, Sharma S, Compton MT, Slade T, & Nielssen O (2011). Cannabis use and earlier onset of psychosis: a systematic meta-analysis. Archives of general psychiatry, 68 (6), 555-61 PMID: 21300939

Rest assured, in this post I’ll be explaining how these concepts are related, and what the latest research has to say about why our brains are so much bigger than they need to be.

Now, about those tits:

Great Tits are gorgeous.

These birds are known to be very social, making songs and calls almost constantly as they communicate within their social groups.

But then you have birds like the Common Cuckoo:

Cuckoos are predominantly solitary birds that rarely get together in groups or pairs, which is one major difference between cuckoos and tits. The other notable difference is that tits have relatively bigger brains than cuckoos…is this a coincidence? Perhaps not, claims recent research out of Dublin, Ireland.

Big brains, big personalities!

It has long been known that the human brain is
larger than science would expect, given the brain-to-body size ratios of other primates. Some might say that the immensity of our brains is proportional to our species’ awesomeness. This might be true. However, a recent computer model suggests that our brains have grown over the course of evolution as we’ve evolved to be social creatures. This model makes sense when considering that bigger-brained primates tend to have larger social groups, and that the same pattern is observed in dolphins.

These researchers in Dublin set out to create a computer model that might help explain this “social brain” or “social intelligence” hypothesis. In short, the scientists started with a computer program representing 50 brains, each with just 3 to 6 neurons. Each brain would then challenge the other to the prisoner’s dilemma or the snowdrift game. The basic premise of both of these games is that each brain has only two options: cooperate and help the other brain get out of a troubling situation (like being in jail or being stuck in a snowdrift), or be more self-serving and do what’s best from a selfish perspective. The researchers even made it so that these virtual brains could learn to remember which brains had helped them in the past, and be more likely to help their previous accomplices in the future.

After 50,000 simulated generations of letting these brains interact, asexually reproduce, and randomly undergo mutations in brain structure or function, the findings clearly showed that increased cooperation led to better-performing brains with greater numbers of neurons. Of course, our brains, and those of primates and dolphins, have infinitely more choices to make than the ones in the computer program had, and we have way more than 3 to 6 neurons (try 80 to 120 billion). But still. This is cool because it’s an attempt to use more than just strict biology to explain something physiologically unexpected — namely, why our brains are so huge. This work comes on the heels of other recent publications that similarly suggest a relationship between social network size and brain size.

And don’t think I’ve forgotten Christina Ricci. Just for funsies, let’s assume forehead size positively correlates with brain size. Here’s a collection of famous people who are either complete social butterflies or total loners, as determined purely by their forehead size.

Happy celebs, with tons of friends, as evidenced by their forefiveheads:From left to right, top to bottom: Christina Ricci, Tyra Banks, Kelsey Grammer, Quentin Tarantino, Mena Suvari, Vince Vaughn, Alexis Bledel, Christian Slater.

Sad celebs who are probably lonely, since their foreheads are so small. Also, natch, there are fewer of them because being famous is such a social experience.From left to right: Katie Holmes, Reese Witherspoon, Mischa Barton, Sandra Bullock.

Remember, the next time someone teases you about your fivehead, tell him you probably have more friends than him, then send him to this post.

Stay nerdy

ten Brink M, & Ghazanfar AA (2012). Social neuroscience: more friends, more problems…more gray matter? Current biology : CB, 22 (3) PMID: 22321306

Kanai R, Bahrami B, Roylance R, & Rees G (2012). Online social network size is reflected in human brain structure. Proceedings. Biological sciences / The Royal Society, 279 (1732), 1327-34 PMID: 22012980

I’ll be honest, I gave a violent video game a try once…but when I found myself sobbing ten minutes into a Resident Evil game for Xbox 360 because a swarm of undead were viciously attacking me from all sides, I decided that whole style of game wasn’t for me. But with video games being an industry that pulls in over $10 billion, and with 40% of games being rated “teen” or “mature,” there are obviously a lot of gamers enjoying violent games.

Many of the gamers enjoying this genre are undoubtedly young males, so it was fascinating to see what Indiana University researchers discovered in the brains of 18-29 year old guys after just one week of playing violent video games.

Up until now, a lot of the speculation about the effects of video games on the people who play them has been correlative. For example, a popularly made point is that kids who play violent video games go on to show more aggression. But then, who’s to say that aggressive kids aren’t just more likely to choose to play a violent game?

But now, a step has been taken to show cause-and-effect between playing violent video games and changes occurring in brain activity. Scientists at Indiana University recruited 28 males between the ages of 18 and 29 (a somewhat small sample size) who had little previous exposure to violent video games. These men were randomly assigned to two groups of 14, and the first group was instructed to play a “shooting game” for 10 hours at home one week, then play nothing the second week. The rest of the men played no video games during the two weeks.

Each of these men had functional MRIs (fMRIs) done at the beginning of the study, as well as at the end of the first and second weeks. This type of MRI can show which parts of the brain are most active. While receiving fMRIs, these men underwent an emotional Stroop test, which essentially tested how the degree to which their brains responded to violent vs. non-violent words.

This testing showed that after a week of playing violent games, the video game group showed less activation in the left inferior front lobe, in an area which I’ve circled in red below (second row, middle):

You can also see that after a week without game play, the gamers’ brains start to look more like those of the controls. While this study has its shortcomings, and it’s hard to say exactly how these changes in brain activity might manifest psychologically or behaviorally, it does show that gaming has a long-term effect on brain functioning. And these results were after a mere week of game play! Most gamers have been playing for years.

The lab that did this study has also researched the effects of violence in the media on adolescent brain activity; perhaps in the future, the combined results of these and other similar studies will have an impact on the restrictions imposed on video games and other forms of entertainment that blend reality with fiction.

Kalnin AJ, Edwards CR, Wang Y, Kronenberger WG, Hummer TA, Mosier KM, Dunn DW, & Mathews VP (2011). The interacting role of media violence exposure and aggressive-disruptive behavior in adolescent brain activation during an emotional Stroop task. Psychiatry research, 192 (1), 12-9 PMID: 21376543

Your new afternoon snacks?

It’s 3PM and you’re at your desk fighting determinedly to keep your eyes open. You think maybe some candy or soda could give you the sugar rush you need to get through the last few hours of the work day, so you head to the vending to get some — STOP! Wait a minute. You might want to read this post first before you snag those M&M’s; new research shows that protein might do a better job of keeping you awake, and burning your calories, too.

As someone who’s happiest with meat at every meal, I say: pass me the jerky.

Everyone’s familiar with the concept of a sugar rush: you eat a ton of sweet stuff, you get a huge rush of energy and hyperactivity, and then you “crash” and feel more tired than you did before eating the sweets. That said, it’s almost logical to think that sugar would stimulate cells that help keep us awake. What cells are those? They are neurons called orexin cells, which secrete a stimulant into the brain to help keep us awake and burn calories. In fact, these neurons are less active in obese people and narcoleptics.

Researchers in the U.K. set out to find what makes these drowsiness-busting, calorie-burning neurons tick. They labeled the orexin neurons in mouse brains using genetically-directed fluorescence; this way, they could introduce different types of nutrients and look at their effects on the activity of only the orexin neurons. Interestingly, glucose was found to inhibit these cells, which might explain after-meal sleepiness when the sugar from your food gets into your blood and then to your brain. In a recent follow-up publication, this same group found that dietary amino acids, like the ones found in egg whites, stimulated orexin neurons — these amino acids even reversed the inhibitory effect of glucose.

In other words, and to vastly oversimplify, sugar might contribute to making you sleepy and stout, while protein could help to keep you lively and lean. These findings could to explain previously mystifying studies in which protein meals made people more alert than carbohydrate meals. Additionally, these results could be especially important for altering the dietary compositions of people with disorders like obesity, insomnia, and narcolepsy.

So, if you swap out a candy bar for a protein bar with the same number of calories, the protein might tell your body to burn more of those calories, and you’ll get through your day with fewer yawns. Sounds like a good trade to me.

Stay nerdy.

Burdakov D, Gerasimenko O, & Verkhratsky A (2005). Physiological changes in glucose differentially modulate the excitability of hypothalamic melanin-concentrating hormone and orexin neurons in situ. The Journal of neuroscience : the official journal of the Society for Neuroscience, 25 (9), 2429-33 PMID: 15745970

Karnani MM, Apergis-Schoute J, Adamantidis A, Jensen LT, de Lecea L, Fugger L, & Burdakov D (2011). Activation of central orexin/hypocretin neurons by dietary amino acids. Neuron, 72 (4), 616-29 PMID: 22099463

Left: actually viewed; right: computer reconstruction based on brain imaging

Well, it looks like the future is finally here. I wasn’t quite sure how it was going to present itself, but it seems to have come in the form of UC Berkeley scientists who have developed a “decoder” that can measure our brain activity and reconstruct our visual experiences. In other words, 20 years from now we might not ask eye-witnesses to describe a suspect…we’ll just analyze their brain activity and reconstruct the suspect’s image for ourselves.

I couldn’t make this stuff up if I tried.

I’ll be honest: I would be way out of my league if I tried to give a technical account of how the decoder works, but this research is so mind-blowing that I had to share it.

The scientists behind this project were dedicated, spending hours being as still as possible inside an MRI machine so that a functional MRI (fMRI) could measure the blood flow through the visual processing centers of their brains while they watched movie trailers. Each second, a computer made associations between the images in the movie and the resulting activity in the brain.

fMRI image

The decoder algorithm developed by these researchers can describe how temporal and spatial information are represented by fMRI data. Five thousand hours of random YouTube video clips were fed into the computer and this same algorithm predicted the types of fMRI responses these clips would elicit. From this, the researchers were able to take the fMRI data generated while movie trailers were viewed, then reconstruct the images seen by the person using composites of YouTube videos that had the most similar predicted fMRI signature to the real data. The results I’m showing below may look crude, but the fact that they’re just based on an algorithmic analysis of fMRI data is incredible. 

On the left is a still from the actual trailer viewed by the subject, and on the right is the composite put together by the algorithm:

A continuous video composite created by the algorithm is embedded below:

The implications of this go far beyond being able to see a fuzzy recreation of something you’ve already seen, or even my hypothetical future scenario of computer-generated criminal suspect renditions. This technology could allow us to have computer-generated versions of our dreams, which we could show to anyone we wanted. People who are physically paralyzed would potentially have an entirely new means of expression. And what would the images generated by a schizophrenic mind look like?

Like I said…the future is definitely here.

Naselaris T, Kay KN, Nishimoto S, & Gallant JL (2011). Encoding and decoding in fMRI. NeuroImage, 56 (2), 400-10 PMID: 20691790

Shinji Nishimoto, An T. Vu, Thomas Naselaris, Yuval Benjamini, Bin Yu, Jack L. Gallant. Reconstructing Visual Experiences from Brain Activity Evoked by Natural Movies. Current Biology, 22 September 2011

Should've been more careful around prions...

When I say that prions are one of the coolest biological phenomena in existence, I mean to say that they are one of the most sci-fi and potentially frightening things you could encounter. They are the causative agent behind mad cow disease, which you’ve probably heard of, and which might not seem too terrifying. But the way prions work, and the fact that there is a “human form” of mad cow disease, will be enough to give you the creeps.

Did I mention that prion infection is the closest thing there is to real-life zombie-ism? Okay, okay, what IS a prion?

So, there are viruses, which are responsible for the flu, and there are bacteria, which cause tuberculosis; these are well-known. Even the lesser-known protists, which give rise to malaria, are similar to bacteria (although more complex in structure). Prions, on the other hand, are an altogether different infectious agent.

In simple terms, a prion is an rebellious protein, a protein that has failed to fold up into the proper configuration. And prions take their frustration out on normal proteins by making them fold up improperly, too, thus propagating more prions. In fact, the word “prion” is a contraction of “protein” and “infection.” How do prions work? Not by any means so taxing as invading a cell and hijacking its DNA, or anything like that. As far as we know, normal proteins fall prey to prions simply by physical contact, thus leading to a domino effect of prion creation, which I have tried to illustrate below (afterwards, I’ll show why prion infection is really, really bad).

Let’s say we start with 20 blissful blue proteins, and they’re blissful because each one of them is a nice square shape:

But then a vindictive prion comes along, and it’s angry because it failed at being a square (and because it has a unibrow):

 So this prion, like a real class act, takes its feelings out on the nearest normal protein by making contact with it:

And what was a normal protein is now a disgruntled, misshapen prion:

It’s all downhill from here. Two angry prions become four:

Four become eight:

And finally everybody is an angry, bent out of shape (literally) prion:

So why does prion infection matter? And what was I saying about zombies? This is where things get interesting.

As it turns out, cells do not like being full of misfolded proteins. The real problem with prion proteins is that they get tangled up and stick together, forming very large, stable aggregates inside of cells. This leads to cell death and tissue damage, specifically in the brain, where prions wreak their havoc. The picture below on the left shows a brain suffering from prion infection, riddled with holes due to tissue destruction (normal brain tissue is shown on the right at a lower magnification):

The effect of prions on the brain is also visible on a macroscopic scale, as seen in these brain sections where the prion-infected brain is on the left and is visibly deteriorated:

When a cow is infected with prions, it has mad cow disease. When a human is infected with prions, he/she has Creutzfeldt-Jakob disease (CJD; not as catchy). The symptoms of CJD start with dementia (memory/personality loss), followed by speech impairment, jerky movements, and poor balance (not to be insensitive, but this could all describe a zombie, no?)

There are three main ways you can end up with CJD: 1) acquire it, by somehow getting prions into your system from the environment, 2) inherit a mutation that dooms your proteins to become prions, or 3) have the bad luck to spontaneously develop prions in your brain.

Fore tribe members

While some people worry about eating beef when mad cow disease breaks out, you would have to consume beef that had picked up traces of brain and prion during processing in order to get CJD. What’s more, this and all  other acquired forms of human prion diseases make up less than one percent of cases. But since I’m on the topic, I’ll briefly mention that there is a tribe in Papua New Guinea called the Fore tribe, and in the 1950s they had an epidemic of a prion disease called kuru. This happened because it was traditional in this culture to eat the bodies (including the brains) of deceased family members. All it would’ve taken was one person with prion disease to die, then the family would’ve eaten prion-infected brain, which would eventually cause all of them to die, and then be eaten…and so on, until cannibalism was banned later in the ’50s. (Eating brains, developing zombie-like symptoms…the connections are hard to ignore.)

So the #1 rule if you don’t want to acquire prion disease is to not eat brains. Unfortunately, the vast majority (85%) of human prion diseases apparently arise sporadically, perhaps from some spontaneous mutation or conversion of normal protein to prion protein. Researchers say there is no amount of prions too small to cause full-blown disease, and once you’re affected there’s no cure and it’s always fatal. The only real variable is that it can take years of incubation before prion levels rise to symptom-causing levels.

I don’t mean to scare you! Despite all this, a human with prion disease is statistically one in a million. If anything, this post will hopefully prove useful to you the next time you’re in the company of nerdy friends, watching zombie movies, and you can sound extra nerdy: a lot of movies depicting a zombie apocalypse rely on the spread of zombie-ism through an aggressive virus, so when that tidbit comes up in the movie, you can turn to your friends and say, “Well, this would be more realistic if the virus precipitated prion formation….”

Stay nerdy!

(Side note: I threw in Max Brooks’s World War Z because it’s one of the best novels I’ve read in recent years — a surprisingly sobering and somehow realistic take on a post-zombie apocalypse world. Also, Patient Zero is the first book in a series that I adore by Jonathan Maberry; this book seriously brings hand-to-hand zombie combat to life.)

 

 

Trevitt CR, & Singh PN (2003). Variant Creutzfeldt-Jakob disease: pathology, epidemiology, and public health implications. The American journal of clinical nutrition, 78 (3 Suppl) PMID: 12936961

Edgeworth JA, Gros N, Alden J, Joiner S, Wadsworth JD, Linehan J, Brandner S, Jackson GS, Weissmann C, & Collinge J (2010). Spontaneous generation of mammalian prions. Proceedings of the National Academy of Sciences of the United States of America, 107 (32), 14402-6 PMID: 20660771

Fryer HR, & McLean AR (2011). There is no safe dose of prions. PloS one, 6 (8) PMID: 21858197

The existence of synesthesia is at least an interesting bit of trivia, and at most the focus of numerous psychological, neurological, and population-based studies. I think many people have heard of it, if not by name then by its description. The rock/hip-hop group N.E.R.D. brought attention to the condition with their highly successful third album, Seeing Sounds. The album title was in fact inspired by synesthesia, which the band learned about while watching the Discovery Channel.

Letters and numbers as they might be seen by a synesthete.

But the most common type of synesthesia, though, is to see letters and numbers (collectively known as “graphemes”) as having particular colors (see left). A rare group of synesthetes tastes words. I was a sound –> color synesthete, triggered specifically by music (not environmental sounds). Some of the known associated traits of synesthesia — photographic memory, left-right confusion, and very little sense of direction — fit me to a T. Others — difficulty with arithmetic — don’t describe me at all. But, as I said, I hardly if ever experience synesthesia anymore, and the few experiences I do have are tainted by my awareness of the phenomenon (e.g. I’ll find myself thinking, “This song should be blue,” rather than just seeing it for what it is). It’s not unheard of for synesthesia to fade during puberty, probably because of all the changes occurring in the brain.

fMRI of grapheme (blue) and color areas (yellow)

So what is happening in the brains of synesthetes?  It could be as simple as cross-activation of specialized parts of the brain, like the part that recognizes graphemes and the part that processes color (they’re adjacent; see right). Some think that synesthete brains have failed to clear out some of the excess synapses that are formed in infancy, so brain areas that would normally be separated remain connected. Recent research suggests that synesthesia might just be at the tail end of a spectrum of normal perceptual processes.

In any case, about 1 in 2000 people have synesthesia, and the specific synesthetic experience can be extremely unique to each individual. While the condition is intriguing (and some people really wish they had it), I wouldn’t say there is any particular benefit to it, although the combination of senses can sometimes improve recall of images, numbers, words, etc. In fact, synesthetes often go through an awkward or uncomfortable moment of realization that their experience is not universal (imagine the look you’d get after announcing, “That song was so green!”).

Some would say that everyone is already a bit of synesthete. Why? Look at the figure below and, without scrolling any further, ask yourself which of these two things you would call “kiki” and which you would call “bouba.”

Funny enough, just about everyone who tries this calls the orange thing a kiki and the purple thing a bouba, even 2.5-year-olds. Apparently, there is some normal cross-talk between the processing of shapes and word sounds. For more on the “bouba/kiki effect,” click here.

So, are you a synesthete? Do you know one? It would be great to hear about your experiences with synesthesia in the comments.

To do your own research on synesthesia, check out these (hover for info):

Bien N, Ten Oever S, Goebel R, & Sack AT (2011). The sound of size Crossmodal binding in pitch-size synesthesia: A combined TMS, EEG and psychophysics study. NeuroImage PMID: 21787871

van Leeuwen TM, Petersson KM, & Hagoort P (2010). Synaesthetic colour in the brain: beyond colour areas. A functional magnetic resonance imaging study of synaesthetes and matched controls. PloS one, 5 (8) PMID: 20711467

Maurer D, Pathman T, & Mondloch CJ (2006). The shape of boubas: sound-shape correspondences in toddlers and adults. Developmental science, 9 (3), 316-22 PMID: 16669803