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29.12.10

brainSCANr: First week recap (cross-post)

Continuing the cross-posting from the brainSCANr blog. I'll only be doing this for a few more weeks, so if you're subscribed to both, please bear with me.

Wow, it's only been a week, but brainSCANr has been quite successful!

We don't have a mailing list yet, so if you'd like to keep updated in the meantime, subscribe to our RSS feed or follow Brad on Twitter. You can see what people are saying about our site at the bottom of this post.

And if you haven't seen it yet, Brad's been quoted in a recent New York Times article on the human connectome.

So far we've had just shy of 10,000 pageviews from 75 countries including Kenya and Iran. The top 5 countries by pageviews are the US, UK, Canada, Germany, and Spain. I'm very pleased to see non-English speaking countries on this list.

Bradley Voytek brainSCANr


Social media seems to have played an important part in brainSCANr's spread, with over 30 shares on Facebook, nearly 100 tweets, and 45 points on reddit.

Here's our first glance at user trends and data examination. Because of the nature of our system, we can also examine search trends. Thus far, our top five search terms have been:

  • post-traumatic stress disorder
  • anxiety
  • amygdala
  • happiness
  • depression

as well as some more... interesting searches. Sex and money are popular: terms like "sex", "erection", "money", "neuroeconomics", and so on. Also "Google". Not sure what people are expecting to find, but I have promised friends to get them Google in the brain.

I'm curious as to what kind of neuroscience zeitgeist we can tap into with this platform. Mind you, the search rankings above are a bit skewed because of some direct links to searches from external sites.

For example, Vaughan Bell over at MindHacks wrote about brainSCANr, but he linked directly to the PTSD graph, so that's definitely skewing our rankings.

"Anxiety", "amygdala", "happiness", and "depression" seem to be purely organic searches on our users' part. That said, we do show "happiness" as a search example on our main page, so I'm sure that's skewing things a bit. Also, I wonder if the up-tick in "amygdala" searches aren't motivated by the recent studies about the amygdala that have been getting a lot of press.


By the way, I love the internet. The Bickart study shows how one's amygdala and social network sizes correlate. But the comments sections in the CNN blog I linked to above are where the real magic happens. The story states:

...keep in mind that the brain is plastic, and it's possible that the amygdala does increase in size in response to social activity.

To which a commentor said:

ExCUSE me? The brain is WHAT? Maybe on the Jersey Shore it is, but where I live, the brain is organic matter.

Anyway, we hope to do some more sophisticated analyses once more time passes and we get more data. I'd love to hear some suggestions regarding what kind of analyses we could do!

28.12.10

brainSCANr: User comments and suggestions

Because very few people know about the blog yet, I'll be cross-posting from the brainSCANr blog here for a while.

Go check out the latest post: User comments and suggestions.

Also, please add the blog to your RSS reader.

Cross-posting:

What a couple of days! Tomorrow I'll do an update on actual usage statistics, but for now I wanted to thank the community and talk a bit about our immediate plans, as well as show you all what people have been saying about brainSCANr.

First, I'm going to be a bit of a broken record for a bit here.

We don't have a mailing list yet, so if you'd like to keep updated in the meantime, subscribe to our RSS feed or follow Brad on Twitter. Because this is a community effort, we wanted to share what people are saying about our site at the bottom of this post.

Bradley Voytek brainSCANr dopamine


Anyway, Jess and I would like to thank everyone for their great feedback, support, suggestions, etc. We've already gotten 40 comments via the site's commenting system. Your suggestions have been great!

Based on users' suggestions, we've now got a list of over 150 new terms we plan on adding to the database after the new year. Mind you, we're both doing this in our spare time, so we can't really devote as much time as we'd like to this project. Nevertheless, we're very dedicated to it.

You'll notice we've got a bit of a teaser above showing our new category for neurotransmitters/neurohormones/etc.

Ladies and gentlemen, the ever-popular: dopamine!

You can see some obvious players here including most of the basal ganglia. There are also strong ties to disease: Parkinson's disease, addiction, depression, and schizophrenia, or to reward, and also a method: PET. This is likely due to the heavy use of PET in studying dopamine binding (such as with raclopride), and other factors.

So stay tuned!

And as promised, here are some great comments from our users, Twitter, etc.

First, some of these are biased from friends of mine, but hey, we'll take the compliments we get :)

"pretty sure that @bradleyvoytek is going to be the next @HansRosling with the brain data visualization that" via @curtischambers

"This is very very cool. Well done! I am always very appreciative when visual perspectives of research are available. Plus this type of thing is fun to sift through. My only wish is that you could provide an option to hide certain categories, or items to help clean up the map a little. But man, this is really great!" via reddit
(Note: we'll be adding that feature soon!)

"This is fantastic! This technology is good for all disciplines, not just neuroscience."
http://www.reddit.com/r/cogsci/comments/eqhu8/a_new_online_tool_called_brainscanr_visually/c1a9wgw
(Note: I've also gotten a lot of these types of comments, and I'd love to expand to other fields.)

"So cool! Brain-data viz. tool for neurogeeks!" via @carlettej

"Congratulations for the work! and specially for the initiative of sharing."

"Your work is making promising connections."

"Many congratulations and thanks for providing such an invaluable source and for helping the neuroscience community to survive the information overload that threatens to engulf us all."

"I think this would be useful if it included neurohormones and names of genes. Another thing that would be really cool would be to have an interactive, manipulable brain "minimap" in the corner where regions can be selected by visually exploring the virtual brain itself, by zooming in and out, selecting particular species, etc. It would be cool to be able to toggle particular protein densities/expression zones as colored overlays."
(Note: such good ideas! We'll do what we can to make these happen!)

"Sweet!!!"

"This is great. Really good job. Only one concern, I did not find a legend indicating what the different colors refer to."
(Note: our bad! Legend coming soon...)

"Wow this is great!"

"Awesome site guys!"

"Hi Bradley, Jessica, I just came across your site via a link from a friend, just want to feedback and say I think the concept and the execution of your idea is great."

"Jessica and Brad, Congratulations. This is a really cool tool. A few quick comments of user experience - - there is no legend I could find for the meaning of colors and symbols in the map. I guess users will get it anyway, but still..... If you are really quick, type a term like 'memory' and hit search or enter, you may miss the drop down list that opens, and then you get the Sorry, "memory" was not found' message. It took me a couple of times to understand that I should wait for the list and pick a more specific term. Anyhow, the site is great and I love the clean and simple design."
(Note: we're working on speeding things up and making the searches more organic as well)

"Hi Brad... this is great!! It's a resource that soooo many brain people are looking for not only when they need quick descriptions but even to get a quick summary of prior research on some area, phenomenon or theory. Plus, it looks like you've made it easy enough to use and the design is clean and pretty. Also I love how you made all of your resources and work public. Anyway, I thought maybe you could include the Brodman areas in here - either as stand-alone entries, or maybe joined with their descriptive counterparts (i.e. Broca's = BA45 & BA46). Good look with all of this. Congratulations, it looks great (I mean it)."
(Note: Brodmann areas will be tough... but we're looking into what we can do.)


"Eeeeeeee - I love it :) I'm going to blog about it when I get my Christmas cards done!! Also, can I put in a request for some white matter tracts? I'm really happy to make a list for you or send you a link to a good atlas?? Thanks guys, and congratulations!!"
(Note: we've got the list of white matter tracts, and the next update will include them!)

"Of course I'm sure everyone has their favorite term they'd like to add, but..."
(Note: haha oh my yes...)

"Really cool concept for a tool"

"Here it is! My vote for the best brain site for 2010. Brain function, modules and connections that are all backed by Pubmed articles all at your finger tips. Click on the manuscript link and you will see a pdf of connections in the brain that if you zoom in enough (lots and lots of zooming) you will be amazed at the detail and be able to follow the various connections."

"wow. this is all types of awesome."

So thanks for the feedback everyone! Keep the suggestions (and compliments!) coming. Cheers and happy New Year.

25.12.10

brainSCANr

Bradley Voytek brainSCANr


So for those of you who are following this and who don't yet know, my wife Jessica and I started a website called brainSCANr.

From the home page:

The Brain Systems, Connections, Associations, and Network Relationships (a phrase with more words than strictly necessary in order to bootstrap a good acronym) assumes that somewhere in all the chaos and noise of the more than 20 million papers on PubMed, there must be some order and rationality.

While this is a very serious academic project that we started to combine our skills and interest, we thought we'd have a bit of fun with it.

We started a blog for the site that will keep people updated with new additions and features as we add them. I'll be blogging about the major changes here, too.

In the mean time, we did a few fun analyses with our framework. Turns out Christmas, Hanukkah, solstice, and Santa appear in the scientific literature!

So read "A brainSCANr holiday", add the blog to your RSS feed, and/or follow me on Twitter to keep up to date about it!

13.12.10

Cognitive enhancement goes Hollywood

ResearchBlogging.org

My pals Kevin and m1k3y over at grinding.be recently posted about a little viral-intent video for the upcoming movie starring Bradley Cooper: Limitless.



I'm intentionally trying to not read too much about this movie beforehand, so I can't really give a plot synopsis beyond what I've gathered from the YouTube video and Wikipedia write-up. But from what I've gleaned, apparently Bradley Cooper's character gets hold of an experimental drug ("NZT"), and quickly finds that it greatly enhances his cognition. Like, to super-human levels, such that he becomes super-focused and an information-integration machine to the point that he can predict the outcome of future events based upon careful observations. Cool stuff! The movie has a ton of potential and could be very fascinating.

Now, for those of you who've been paying attention, this is a bit of an old topic. Scientists and bloggers have said pretty much everything that can be said regarding the ethics of cognitive enhancement. I can't really add too much, so I will instead direct you toward the relevant information.

There was a commentary in Nature a few years back titled, "Towards responsible use of cognitive-enhancing drugs by the healthy," by some big name ethicists and neuroscientists. They take a nootropic-positive viewpoint, but offer some careful, cautionary words.

That commentary was released around the same time as the famous Nature cognitive enhancement poll of scientists that showed that 20% of scientists had used nootropics.

Bradley Voytek nootropic Nature


Not surprisingly, this got a ton of press, especially in new-media outlets such as Wired and boingboing. (It's also worth reading the April Fool's prank coordinated by PLoS Biology EiC, Jonathan Eisen, with his conspirator, Bora Zivkovic, among others, about this topic.)

I've long been a fan of science fiction and, as I get older, I've also come to appreciate the role that sci-fi plays in non-fi society. Science-fiction can bring difficult topics of future possibilities into the cultural zeitgeist and get people talking about them. It can also help generate entirely new ideas to inspire future scientists and engineers. There's a great discussion from April of this year on NPR about just that. Specifically, Ira Flatow from Science Friday interviews Michael Okuda about the work he and his wife, Denise Okuda, did for Star Trek: The Next Generation. Both of them worked as set and prop designers, and supposedly their work inspired the iPad, 23 years later. (Stories such as that abound in U.S. science and engineering!)

So anyway, I'm looking forward to the movie. Hope they do the topic justice.

Greely, H., Sahakian, B., Harris, J., Kessler, R., Gazzaniga, M., Campbell, P., & Farah, M. (2008). Towards responsible use of cognitive-enhancing drugs by the healthy Nature, 456 (7223), 702-705 DOI: 10.1038/456702a

Maher, B. (2008). Poll results: look who's doping Nature, 452 (7188), 674-675 DOI: 10.1038/452674a

9.12.10

The neuroscientific study of hallucinogens

Bradley Voytek Baggott MDA


ResearchBlogging.org

Recently, an important and landmark paper was published in PLoS ONE (hooray open access!) titled, "Investigating the Mechanisms of Hallucinogen-Induced Visions Using 3,4-Methylenedioxyamphetamine (MDA): A Randomized Controlled Trial in Humans". It sounds daunting, but trust me, it's a very cool, approachable study.

Now, in the spirit of full-disclosure, the lead author Dr. Matthew Baggott (hereafter referred to as "Matt"), is a friend of mine from grad school and he's been kind enough to grant me a very thorough interview for this post. The interview is quite long, so I'll give a brief overview of the research and some of Matt's comments, but I've posted the entire interview at the bottom of this post. And please, take some time to read the entire interview. Matt gives some fascinating historical context about drug research, mathematical models of visual hallucinations, the origin of the phrase "set and setting", and some personal insight into the difficulty of getting a study such as this approved by the DEA, FDA, and IRB!

At the bottom of this post you will also find an hour-long YouTube interview with Matt about his research as part of "Dr. Kiki's Science Hour".

That said, my real-life association with Matt is not biasing my opening statement; his paper is truly landmark for many reasons. This study is the first experiment in which humans were given MDA in over thirty years, and one of only a handful of peer-reviewed publications involving the administration of hallucinogens in as long. Regardless of my views (or yours) on the politics of drugs, the broad class of hallucinogens have incredibly interesting perceptual and cognitive effects (quite the understatement!) that merit neuroscientific research. Why? Because there are subtle and not-so-subtle cognitive and behavioral differences that can be fairly consistent within and across these drugs across people. We neuroscientists can leverage these differences to help us examine questions of perception, cognition, and behavior in a way that is otherwise impossible. As Matt says:

[T]here is a staggering diversity of hallucinogens out there: hundreds of compounds, each affecting different combinations of binding sites in the brain. Research in rats and anecdotal reports from humans tell us that these drugs have really different phenomenology. This is really obvious in the perceptual domain. For example, some hallucinogens cause profound visual distortions, making it almost impossible to see real objects during peak effects. Others have almost no visual effects, just the non-perceptual hallucinogen effects. The range of reported phenomenology is so broad, it starts to seem like we're discussing multiple pharmacological classes, which I think we are.

The range of drugs really is quite amazing, and many hallucinogenic compounds were first synthesized by a fellow Berkeleyan, Alexander Shulgin. Matt continues:

There is even one drug (diisopropyltryptamine) that is said by people to mainly just distort auditory perception, like some kind of flanger or nonlinear pitch shifter, with few other effects. The relationship between phenomenology of these drugs and their pharmacological profiles in the brain is really mysterious. And we're never going to figure it out by just studying one drug. Studying MDA is part of a long-term, audacious, and probably doomed-to-fail project of trying to relate phenomenology and cognitive neuroscience, on the one hand, to molecular-level pharmacology, on the other.

Matt used three tasks (such as the one illustrated below) to assess perception in his subjects during a placebo condition as compared to the drug-challenge. Overall, they found that:

Participants reported that MDA administration was followed by a number of prototypical hallucinogen effects… [that] support our approach of using MDA to understand hallucinogen-induced visions despite the caveat that MDA has complicated pharmacology and is relatively unstudied.

MDA had significant perceptual effects… Magnitude of closed-eye visuals after MDA was associated with lower performance on the two measures of perceptual organization. In both cases, there was also a significant interaction with dosing condition, suggesting that individuals who saw more intense closed-eye visuals both had poorer overall performance on these tasks and also had greater MDA-induced changes in perceptual performance.

Bradley Voytek Baggott MDA


As Matt's study demonstrated, these perceptual effects can tell us a bit about visual processing while simultaneously demonstrating, in a controlled, scientific setting, that these effects can be studied without any adverse medical effects. In fact, in this study, the participants were in a very controlled, scientific (read: not very stimulating) setting:

I'm quite certain that these studies are a lot less fun and a lot more tedious than taking hallucinogens with their friends or loved ones. Clinical research is often pretty boring, especially when the researchers are asking you to do strange computerized tasks that have no clear relevance to the psychedelic trip. We usually try to explain, as much as we can, study tasks so that they do not seem arbitrary and we try to make them as interesting as we can. But they're never as fun as real computer games. On the other hand, this was a fairly short study – just one long weekend. So it probably didn't get too boring. And, for many hallucinogen users, there is something interesting about getting a known dose of a pharmacologically pure drug.

Now realize, I don't make my statements about drug research lightly. I understand full-well the negative aspects of drug abuse and addiction. It is important to note that there are clinical differences between drug "use", "abuse", "dependence", and "addiction", as compared to casual/recreational use. In my past neuroscientific life, I worked as a PET scanner operator at UCLA for two years with methamphetamine abusers and published several publications on brain changes associated with methamphetamine poly-drug interactions and recovery from chronic methamphetamine abuse. These studies are what initially got me interested in the role of neuroplasticity in cognition.

Overall, this is a great study and really an important step for future human neuroscientific research with cognitively-active compounds. While there are certainly limitations to this study (about which the authors are quite forthcoming), they don't detract from the overall importance of the paper.



FULL INTERVIEW
The Griffiths study gained a lot of attention and really helped reignite the scientific study of hallucinogens. It strikes me that the Griffiths et al. experiments are purely behavioral, whereas yours add a cognitive/perceptual component. How do you see your study as expanding on Roland's work and why do you consider this an important next step in human drug research?

I think you hit the nail on the head. We take an approach that uses cognitive neuroscience and psychophysics to investigate brain mechanisms. Another obvious, but I think important, difference is that we are looking at a different drug. Almost all legitimate human hallucinogen research uses psilocybin. Yet there is a staggering diversity of hallucinogens out there: Hundreds of compounds, each affecting different combinations of binding sites in the brain. Research in rats and anecdotal reports from humans tell us that these drugs have really different phenomenology. This is really obvious in the perceptual domain. For example, some hallucinogens cause profound visual distortions, making it almost impossible to see real objects during peak effects. Others have almost no visual effects, just the non-perceptual hallucinogen effects.

The range of reported phenomenology is so broad, it starts to seem like we're discussing multiple pharmacological classes, which I think we are. There is even one drug (diisopropyltryptamine) that is said by people to mainly just distort auditory perception, like some kind of flanger or nonlinear pitch shifter, with few other effects. The relationship between phenomenology of these drugs and their pharmacological profiles in the brain is really mysterious. And we're never going to figure it out by just studying one drug. Studying MDA is part of a long-term, audacious, and probably doomed-to-fail project of trying to relate phenomenology and cognitive neuroscience, on the one hand, to molecular-level pharmacology, on the other. MDA seems to be a drug with similarities to classical serotonergic hallucinogens (like psilocybin and LSD). But it also has many similarities to its chemical cousin, MDMA ("ecstasy"), which many people argue is not really a hallucinogen at all.

Unlike classical hallucinogens, MDMA has very consistent emotional effects, which many people describe as feelings of empathy and emotional closeness to others. In our study, MDA seemed to share some of these consistent emotional qualities. Dave Nichols has suggested the term "entactogen" (which basically means "touchy-feely", or "generating touching within" if you want to be precise about it) for drugs with these unusual emotional effects. We and others have evidence that these so-called entactogen effects are related to serotonin release. I take a state-space or dimensional approach to understanding these drugs. Instead of seeing them in discrete categories, I think it is helpful to consider them as having different amounts of underlying characteristics, although it is not yet clear how many of these characteristics or dimensions there are.

Most classical hallucinogens share a tendency to cause altered sense of self — what the psychiatrists call "depersonalization" and mystics call "ego loss" — and the feeling of changed reality. And, as I said earlier, there is a perceptual effects dimension along which different hallucinogens very. How many more dimensions of effects we'll find is anyone's guess. Personally, I suspect that much of the remaining variance will be captured in a small number of dimensions, many of them having parallels in the literature on affect and personality. For example, the MDMA-like dimension may end up relating to extraversion and decreased harm sensitivity.

So one way that we are building on Roland's work is by characterizing another hallucinogen and seeing that it is also shares some potential for making mystical-type experiences more likely. In a way this isn't surprising. After all, religions like the Native American Church and the Santo Daime regard certain hallucinogen-containing substances as sacraments. Yet, I'm not certain we as a society have sufficiently grappled with the implications of this. Some of Roland's colleagues have suggested that this makes it possible to conduct rigorous empirical research on the psychology of religious experience. Instead of just looking at statistical correlations, one can prospectively assign people to pharmacological conditions in which mystical-type experiences are likely. The possibility that your study might cause someone to find religion or change their life direction is a sobering thought. I know that this is an area that they have thought through very carefully over at Hopkins.

One of the reasons that my studies only include experienced hallucinogen users is that any big hallucinogen-related insights or life changes have probably already occurred. Thus, being in the study is not likely to cause a participant to change their name to Suzy Creamcheese, go on tour with a jam band, invent PCR, or write "One Flew over the Cuckoo's Nest".


Other than Roland Griffiths, what other researchers are currently and actively studying the behavioral effects of hallucinogens?

To my knowledge, most of the human studies with hallucinogens focuses on whether hallucinogens can help specific patient groups. For example, there are two groups in New York looking at whether psilocybin (the psychoactive chemical in psychedelic shrooms) can help people with cancer feel less distress. Someone in Switzerland is doing a small trial of LSD psychotherapy, sponsored by MAPS.

There are fewer examples of groups doing what we do, that is, using hallucinogens as scientific tools rather than potential medicines. Franz Vollenweider's group in Switzerland, with funding from the Heffter Research Institute, has been very productive in this area for many years. Right now Robin Carhart-Harris is lead researcher on an interesting psilocybin fMRI study in England, sponsored by the Beckley Foundation. (In this answer, I am not considering MDMA as a hallucinogen. If we included it, there would be a couple more groups in both categories, including some NIH-funded projects.)

As you can see, aside from some research with MDMA, human studies with hallucinogens are mostly privately funded by groups like the Beckley Foundation, MAPS, and the Heffter Research Institute. These are, in turn, supported by small foundations and, as they say, "viewers like you." Much of the Renaissance in human hallucinogen research in the late 90s and early 2000s can be traced back to a small number of people, such as the now deceased Bob Wallace, an early Microsoft employee. The dominance of private funding in this field is interesting. It probably allows greater innovation, but it also may subtly influence scientists to study accessible, easily publicized topics and run smaller (cheaper, but often statistically underpowered) studies. By the way, as I note in the paper, I received some Beckley Foundation funding that was very important for helping me to develop study measures.


You mention it briefly in your paper, but can you give a lay-introduction to the Ermentrout and Cowan model of hallucinations?

Bard Ermentrout worked with Jack Cowan in the late 1970s to develop a formal model of the simple pattern visuals that often occur shortly after hallucinogenic drug administration. Their research elegantly connected some observations first made by German neurologist Heinrich Klüver to a field of research pioneered by British genius Alan Turing. Klüver is now famous for co-discovering Klüver-Bucy syndrome in monkeys, but he came upon that syndrome while trying to understand the effects of the hallucinogen mescaline. As part of his research, he took mescaline many times himself, enough times to start to notice commonalities in how the visuals progressed over a trip. He organized the visuals into categories he called "form constants" and wrote a lovely little book about it.

Over the years, this work was more or less forgotten (when Ronald Siegel at UCLA started categorizing the perceptual effects of hallucinogens, he initially didn't know about Klüver and independently replicated many of Klüver's categories). Ermentrout and Cowan realized these patterns could be related to work on something called diffusion-reaction systems, which had been pioneered by Alan Turing. After he made important breakthroughs in computer science and helped to win World War II (and shortly before he was persecuted to death for being homosexual), Turing got interested in explaining the complex mathematical patterns that we see in nature.

He figured out that you can get spontaneous formation of elaborate patterns under certain conditions of diffusing excitatory and inhibitory processes. For example, the patterns on many different animals' coats can be explained if you hypothesize that there are two chemicals diffusing through the animal as it develops: an excitatory chemical that makes the skin or fur darken and an inhibitory chemical that prevents this. If the excitatory chemical causes cells to make more of both chemicals and the inhibitory chemical causes cells to make less of both chemicals, then — with some model parameters — you can get elaborate patterns like zebra stripes and leopard spots that seem to appear out of nowhere.

A really cool thing about this is that the pattern complexity in these models depends on how much space the pattern has to form in. And you can really see this by looking at animals. It is only the medium large animals that have neat patterns. Really small or really large animals don't have patterned surfaces at all. You don't see tiger-striped mice or whales. Kind of small animals, like hamsters, at best have pathetic wannabes patterns, like large irregular blotches. And if you look at an animal that has nice patterns on its body, the patterns often break down in the limbs where there is less space for pattern formation.

Ermentrout and Cowan realized that a similar process in the brain could explain hallucinogenic visuals. Only instead of excitatory and inhibitory chemicals diffusing, you have excitatory and inhibitory neurons firing and making neighboring neurons more or less likely fire. They proved that, if you take a simple idealized sheet of cortex, you can get spontaneous formation of stripes of alternating firing and silent neurons. Then they asked what these stripes would look like if the pattern formed in one's visual cortex. The answer depends on the angle of the stripes on the cortex. This is because the large "primary visual cortex," where visual information first enters the cortex, gets a lot more detail from the center of your vision than it does from the edges, which means you want to use more of the cortex to process the center of the vision. The result is a funny (roughly log-polar) transformation between images hitting the retina and how they get represented in primary visual cortex.

Ermentrout and Cowan reversed this transformation to calculate how stripes would appear if they were "projected" into visual space. It turns out that, depending on the stripe angle, you see spirals and tunnels and other things that are pleasingly similar to form constants described by Klüver! This type of modeling is now a substantial area of research. In fact, Ermentrout just co-authored a nice textbook with David Terman on the mathematical foundations of neuroscience.

These models lead to a spontaneous pattern formation theory of hallucinogen-induced visuals. One implicit aspect of this theory that I haven't seen clearly discussed in the literature is that the approach may be able to explain the increasing complexity of visuals that occurs over the course of a single hallucinogen experience. Just as tiger stripes form most readily on the large body of an animal and not on its limbs, you would expect stripes of neural excitement to also form most readily in the large primary visual cortex and not in the smaller visual areas. Thus, the first spontaneous patterns to form during the hallucinogen trip would be in primary visual cortex and would represent the sorts of computations done in that brain region: detailed line segments. This would explain why Klüver's form constants happen relatively early in a trip. Once you get stable patterns there, the perceived patterns may be passed on to hierarchically higher and physically smaller visual areas that make more advanced interpretations of the visual scene. That might be when you start to see objects embedded in the abstract visuals. Ultimately, the pattern might spread to areas representing scenes, at which point the individual would hypothetically experience detailed immersive virtual reality experiences, as some people report after high doses of hallucinogens.

It is a beautiful theory. The thing is, there is almost no empirical evidence supporting it. A critic might say that just about anything projected from cortical to visual space will look trippy. One of the only pieces of evidence I can think of is that this pattern formation theory can also explain the existence of flicker-induced visuals and we know that visual flicker potentiates the visual effects of low dose hallucinogens, suggesting a possible common mechanism.

So one thing that we tried to do in this MDA study was to make a very modest step in the direction of testing this theory. We took a visual illusion that is thought to involve primary visual cortex and tried to see if the magnitude of the illusion was altered in people when they were on MDA. Unfortunately, we didn't get conclusive evidence one way or the other. However, I'm really proud of the attempt to find links between experience and formal theory, even if we failed to prove or disprove anything this time.


We’ve talked about it informally, but can you say anything "on record" about the difficulty in getting all the required approvals to run this experiment?

Studies where you give controlled substances to humans are closely regulated by a whole bunch of federal, state, and local organizations. I'm not against this: We definitely should be cautious about research that can change people's lives. There is a lot of potential for things to go wrong. One unfortunate side effect of having so many agencies involved, however, is that it is difficult to estimate how long it will take to navigate the regulatory maze. You need to get permission from the FDA, DEA, IRB, state of California, and probably your department chair. A one-month delay from one agency can domino into a six-month delay in starting the project and if anyone says no, the project is finished. This makes initiating hallucinogen-related projects high risk for young scientists who need to publish. You might spend a year killing trees and never have anything flower.


Tell me a little about the set and setting the subjects were in.

The physical setting was nothing particularly fancy. It was the General Clinical Research Center at San Francisco General Hospital. I sometimes wish that we had the budget to deck out a chill space with a sweet sound system and artwork like they did at Johns Hopkins, but I suspect the people are more important than the decor anyway. When I first started conducting studies with MDMA, I really worked to make the experimental rooms as nice as I could. I eventually learned that people on MDMA will be pretty content in any room.

Interestingly, I don't think anyone has ever actually shown that mental set and physical/social setting are more important for predicting the effects of hallucinogens than they are for other drugs. In general, correlations between pre-dose psychological measures and peaked effects have been pretty unimpressive. Of course, this might just be because most studies do a pretty good job of being nice to their participants.

Or maybe "set and setting" are not that important. The phrase has an interesting history. There was a great deal of interest in early psychopharmacology in explaining the variability in drug effects, both hallucinogenic and non-hallucinogenic. Psychopharmacologists like Hans Eysenck and Max Rinkel looked at "non-specific influences" on drug response and many researchers used the individual words, set and setting. But the pairing of those two words as a phrase was popularized by Timothy Leary much later, at a time when opinion about hallucinogens was very polarized.

In a way, it seems to me that the phrase partly served to shift blame for "bad trips" or negative clinical trials from the drugs and onto the drug users and researchers. It was sometimes used as a way of saying that, if you didn't achieve mystical enlightenment, you weren't "doing it right." But the truth is, I don't think anyone can reliably predict pleasant versus unpleasant hallucinogen experiences. That being said, I think it is useful to consciously remind ourselves at the beginning of experimental sessions that the purpose of the session is scientific: that our goal is to bring back knowledge that we hope will be useful to society. I don't know if this "establishing intent" actually has any effects on the participant or improves the quality of data we collect, but I suspect it does.


These were all experienced drug users. How was the experience for them in such a controlled, three-day, medical, scientific setting?

I'm really grateful to our heroic participants, who loaned their consciousness to science for the duration of the study. I'm quite certain that these studies are a lot less fun and a lot more tedious than taking hallucinogens with their friends or loved ones. Clinical research is often pretty boring, especially when the researchers are asking you to do strange computerized tasks that have no clear relevance to the psychedelic trip. We usually try to explain, as much as we can, study tasks so that they do not seem arbitrary and we try to make them as interesting as we can. But they're never as fun as real computer games. On the other hand, this was a fairly short study – just one long weekend. So it probably didn't get too boring. And, for many hallucinogen users, there is something interesting about getting a known dose of a pharmacologically pure drug.


What’s next?

We are now working on analyzing the blood samples we collected and comparing our MDA results to our past studies with MDMA. We are also reaching a good publishing point in a project of analyzing the language people use to describe hallucinogen experiences. More generally, I remain very interested in how MDMA alters emotion and what this can tell us about the function of serotonin.


Anything important you’d like to add?

While studies in a controlled clinical setting with carefully screened and prepared volunteers are low risk, MDMA and related drugs have real potential for toxicity. People sometimes have idiosyncratic reactions for reasons no one understands. Women seem to be particularly susceptible to developing hyponatremia (low salt in the blood), which can be fatal, after MDMA. We are currently studying this issue. Right now, no one knows if this only happens to people who drink a whole lot of water. One possibility is that MDMA may cause release of antidiuretic hormone and make it harder for your body maintain the right water balance even when you drink normal amounts of water. Some are suggesting that sports drinks might be the safest thing to drink on MDMA. This is an important area that needs more research.

Like much of science, hallucinogen research is an area where you can only succeed by collaboration. The research participants, the visionaries funding this area, the nurses and technicians, and very many formal and informal scientific advisors were all crucial to the study.

Baggott, M., Siegrist, J., Galloway, G., Robertson, L., Coyle, J., & Mendelson, J. (2010). Investigating the Mechanisms of Hallucinogen-Induced Visions Using 3,4-Methylenedioxyamphetamine (MDA): A Randomized Controlled Trial in Humans PLoS ONE, 5 (12) DOI: 10.1371/journal.pone.0014074

Griffiths RR, Richards WA, McCann U, & Jesse R (2006). Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology, 187 (3) PMID: 16826400

Voytek B, Berman SM, Hassid BD, Simon SL, Mandelkern MA, Brody AL, Monterosso J, Ling W, & London ED (2005). Differences in regional brain metabolism associated with marijuana abuse in methamphetamine abusers. Synapse (New York, N.Y.), 57 (2), 113-5 PMID: 15906384

Berman SM, Voytek B, Mandelkern MA, Hassid BD, Isaacson A, Monterosso J, Miotto K, Ling W, & London ED (2008). Changes in cerebral glucose metabolism during early abstinence from chronic methamphetamine abuse. Molecular psychiatry, 13 (9), 897-908 PMID: 17938635

8.12.10

Endogenous Electric Fields May Guide Neocortical Network Activity

ResearchBlogging.org
(Note: this is a repost of my original post from 2010 Jul. I'm reposting some old posts to work within the ResearchBlogging.org framework.)



I’ve been geeking out about this paper for a week or so now, so I just finally decided to put together a post about it to explain why I think it’s so awesome.

I’ve been thinking about the foundations of electrophysiological research in neuroscience. The earliest experiments on the electrical properties of neurons were performed on giant squid axons because the axons in these animals are quite large and thus easy to record from. That is, the axons are visible to the naked eye, which means they’re very easy to insert recording electrodes into. From the earliest (Nobel Prize winning experiments) by Hodgkin and Huxley in the 1930s and 40s it was shown that neurons communicate via the transmission of electrical “all or none” action potentials. Decades of biochemistry and electrophysiology in the intervening years have shed a lot of light on the biological and biophysical mechanisms that give rise to these action potentials.

Of course, one of the major outstanding questions in neuroscience is how do you go from millions of individual neurons firing these rapid, near-impulse electrical potentials to a unified behavioral and cognitive experience?

Over the last decade there has been an explosion in the role that endogenous, electrophysiological oscillations play in cognition. To unpack that a little bit, back in the 1920s Hans Berger (about whom I need to write a whole post) found that if you use sensitive recording electrodes attached to the scalp, you can pick up the electrical activity of the brain. As an aside, interestingly these first experiments were performed on patients with small holes in their skulls because the electrical signals were better. I conducted an entire experiment just looking at this phenomenon. Again, decades of research have shown that these electrical fields probably represent the summed activity of millions of synaptic electrical potentials. That is, in order for an action potential to fire, ion channels open in each neuron changing the flow of electrical charge into and out of the cell. Millions of these charges sum together (it’s complicated) and these summed charges can be picked up using EEG.

With EEG (either on the head, outside the skull, or implanted inside the skull onto the brain), really clear oscillations can be observed. In fact, these oscillations are so obvious, that Hans Berger noticed them early on.

Hans Berger EEG

It turns out that the amplitude of these oscillations is modulated by cognitive tasks. Sometimes they oscillate faster or stronger, sometimes slower or weaker. Using math (and science!) we can easily show that different parts of the brain seem to have “preferred” oscillations. No one is sure why. Using even more math, my friend and colleague Ryan Canolty (among others) showed that when slow oscillations are at their lowest points, you’re more likely to see an increase in neuronal activity. I’ve got a paper coming out soon (that I’ll surely write about here) showing that this effect depends on the frequency and location in the brain of the slow oscillation, as well as what the person is doing.

Anyway, it’s often interpreted that the slow oscillation represents the extracellular membrane potential. That is, the space in between neurons has a charge, and if this charge is a little lower (the trough of the slow oscillation) then neurons are more likely to fire (more activity). If the charge is larger (the peak) then neurons are less likely to fire (less activity).

So what’s really been twisting my noodle is that maybe this interpretation is wrong. Maybe across millions of years of divergent evolution, the axon of a giant squid has evolved to perform computations necessary for the survival of giant squids, and maybe mammalian neurons have evolved somewhat differently. Maybe individual action potentials are important in humans, but maybe they’re not the only things doing “computing” in the brain. Maybe these oscillations are also playing an important computational role. Maybe they’re not just epiphenomena of action potentials. But maybe there’s a complex feedback system between action potentials and oscillations.

And that’s just what Flavio Fröhlich and David McCormick have shown. And that’s why this paper is awesome. I’m pretty sure that the more research that’s done on this topic, the more it will be shown that oscillations are pretty key players in this whole consciousness and cognition thing.

Fröhlich F, & McCormick DA (2010). Endogenous electric fields may guide neocortical network activity. Neuron, 67 (1), 129-43 PMID: 20624597

1.12.10

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<Introduction>
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Bradley Voytek Upper writer's block


<Methods>
Duis mollis malesuada ipsum, et interdum felis blandit eu. Vestibulum id purus odio, vitae bibendum mauris. Aliquam tristique, quam et pellentesque commodo, nunc lacus porta nisi, id faucibus urna nisi quis dolor. Praesent tortor metus, vehicula in posuere at, blandit vel lorem. Duis lacinia gravida porta. Nam fringilla pharetra dignissim. Sed viverra scelerisque ligula nec cursus.

<Results>
Cras nec nisi non velit tincidunt accumsan sit amet in lorem. Sed euismod dolor non massa pharetra fermentum lobortis orci lacinia. Class aptent taciti sociosqu ad litora torquent per conubia nostra, per inceptos himenaeos. Proin eleifend varius odio, vel lobortis mauris fermentum vel p<0.05.

<Discussion>
Aliquam augue dui, lacinia quis tincidunt id, tempus a quam. Nunc fermentum varius eros in mollis. Pellentesque non purus at urna malesuada rutrum vitae in enim. Maecenas ac lorem leo, a adipiscing enim. In tempor dui id lectus adipiscing id volutpat urna pulvinar. Aliquam sit amet sollicitudin urna. Integer imperdiet elementum sapien, eu blandit nisl auctor vel.



ResearchBlogging.org
Upper D (1974). The unsuccessful self-treatment of a case of "writer's block". Journal of Applied Behavior Analysis, 7 (3) PMID: 16795475

30.11.10

Voytek Journal of Cognitive Neuroscience paper: "Hemicraniectomy: A new model for human electrophysiology with high spatio-temporal resolution"

(Note: this is a repost of my original post from 2009 Dec. I'm reposting some old posts to work within the ResearchBlogging.org framework.)

Bradley Voytek hemicraniectomy


This paper grew out of an interesting collaboration with some physicians at the University of California, San Francisco and San Francisco General Hospital, initially through a meeting between Dr. Geoffrey Manley, Dr. Robert Knight, and I. Dr. Manley has recently published several papers on the clinical benefits of performing a decompressive hemicraniectomy on people who have had some kind of head trauma. To give a little bit of a background, a decompressive hemicraniectomy is a surgical procedure in which the surgeon actually removes a large part of the skull (see the picture at the right) after someone has had head trauma that has caused the pressure inside the skull to increase. This can happen in a few ways, but basically, because the head is an enclosed system,  if the brain swells arteries can get pressed closed. This can cut off the blood supply to different brain areas. The swelling can also cause the brain to press down onto the brainstem which can lead to coma or death.

These folks go without a big piece of their skull for several months. If you're paying attention, that means... yes... there's not a whole lot protecting their brains. As you could imagine most of them wear helmets during this time. Also, some of them actually have the piece of their own skull surgically placed inside their abdomen so that the skull tissues can be kept alive before the get their skull surgically put back in!

Working with these patients gave us a unique opportunity as cognitive neuroscientists. Most of my research uses EEG to examine attention and memory processes. One of the things about EEG is that you can't accurately locate where in the brain something is happening, but you can know when it happens with excellent accuracy. However, because these patients literally have a window onto the brain we can get a much better idea of where the signal we're recording is coming from. And, for a variety of reasons, the signal quality is better over this window.

Our lab does a lot of work with humans who have had electrodes surgically implanted directly onto their brains (I'll write a more in-depth post about this topic in the near future when one of my papers on this topic is published). Because of this I see a lot of really clean data from the intracranial recordings that looks much better than the data we see in normal scalp EEG. So we decided to try and quantify these differences to a certain extent, and thus ran this study.

So in this paper we set out to quantify how the brain signals we record in EEG are different between the side of the head with the skull and the side of the head without. And because the signal quality is better, we can do a few cool things with it... like predicting when a person squeezes their hand just by looking at the brain signal.

It was a fun project, but a bit tricky to run.



Voytek B, Secundo L, Bidet-Caulet A, Scabini D, Stiver SI, Gean AD, Manley GT, & Knight RT (2010). Hemicraniectomy: a new model for human electrophysiology with high spatio-temporal resolution. Journal of Cognitive Neuroscience, 22 (11), 2491-2502 PMID: 19925193

29.11.10

Quick note: ResearchBlogging.org

So I've decided to try out ResearchBlogging.org, which is a site that aggregates any member's blog posts that cite peer-reviewed research. It's a neat, simple system that works via RSS tracking, and apparently the PLoS family of journals uses blog posts made via ResearchBlogging.org as a measure of impact.

Because half of my posts are about peer-reviewed research (although, much of it is about papers more than 100 years old!), I've decided to give it a shot.

What this means to my readers is that I'll be re-posting my older posts on peer-reviewed research so that it will get posted via RSS. I apologize if this is at all annoying to anyone.

26.11.10

Cargo cults of the brain

During World War II, Japanese and American troops operated in large sections of Melanesia. Both sides brought in huge amounts of food, equipment, and supplies for their troops, though by the end of the war the US occupied this region. These islands were inhabited by small indigenous tribes who had never seen such abundance.

After World War II the US abandoned their posts, stopped bringing in supplies, and left the islands. Over time, certain members of the tribe began mimicking the behaviors of the soldiers they had previously seen bringing in vast amounts of wealth. According to Wikipedia,

Cult behaviors usually involved mimicking the day to day activities and dress styles of US soldiers, such as performing parade ground drills with wooden or salvaged rifles. The islanders carved headphones from wood and wore them while sitting in fabricated control towers. They waved the landing signals while standing on the runways. They lit signal fires and torches to light up runways and lighthouses.

In a form of sympathetic magic, many built life-size replicas of airplanes out of straw and cut new military-style landing strips out of the jungle, hoping to attract more airplanes. The cult members thought that the foreigners had some special connection to the deities and ancestors of the natives, who were the only beings powerful enough to produce such riches.

Bradley Voytek cargo cult airplane


The tribes didn't understand how the US troops has access to so much wealth. To try and get at that wealth themselves, they simply mimicked the behavior of the troops. Obviously this is a fallacy: mimicking the behavior of a thing is not the same as understanding the thing. To put it another way:

The map is not the territory.

In 2010, we have major neuroscientific endeavors such as the Blue Brain Project. According to this group,

The facility has been used to build the first model of the neocortical column, which consists of 10,000 3D digitizations of real neurons that are populated with model ion channels constrained by the genetic makeup of over 200 different types of neurons. A parallel supercomputer is used to build the model and perform the experiments so that the behavior of the tissue can be predicted through simulations.

Bradley Voytek blue brain project


Maps? Territories? As I said in my old post on the subject,

To think that modeling a bunch of neurons digitally is akin to a thinking, evolved, conscious, aware human brain is like thinking that by soldering together a couple of million transistors in a "Apple-like fashion" will give you a working MacbookPro.

Now, I swear I'm not picking specifically on Blue Brain. I love Blue Brain. I want Blue Brain to succeed. I'm a huge sci-fi nerd! I want my cool brain-computer interfaces, AI, etc. When I wrote a skeptical post about the Blue Brain Project back in July, there were a few challenging comments written in response. However, my critiques of this project are certainly not the only ones.

When the project first started up in 2005, Nature ran a brief news piece on the Blue Brain Project wherein they discussed some of the very same concerns I voiced in my post.

This is an ambitious project that is bound to fail," says Terry Sejnowski of the Salk Institute for Biological Studies in San Diego, California. "We are still far from understanding enough about the brain to build a detailed realistic model."

Neuroscientists say that too little is known about the structure of the network connecting cortical cells, for example. They add that a truly realistic model would have to incorporate molecular activity in the regions where neurons connect, a level of detail that is currently beyond the Blue Brain Project.

Right. Well, at the time of my posting, I hadn't read that, but that was pretty much what I said:

...[A]t this point we honestly just don't know enough about how all the pieces play together to give rise to our cognition. I think the neurosciences right now are where physics was in the early 1900s. A bunch of people thought Newtonian mechanics could explain everything. Turns out, the physical universe is much more complicated than that....

...[W]e know a lot about the biology of the neuron. Similarly, computational modeling has gotten very sophisticated. When researchers build computational models incorporating known biology, they call it a "biologically-plausible" model. I think we're still stuck in the Newtonian mechanics period of neuroscience, and we're just now segueing into the more complicated "oh my god this stuff is harder than we thought!" part of our science.

However, people seem to think that the fact that I don't believe that the Blue Brain Project, as currently instantiated, will give us a human brain model somehow translates to me thinking that the Project shouldn't be done. As I said in the comments to my post,

Blue Brain's an excellent step in the right direction. However the people selling it are over-hyping what we do know in neuroscience.

There's a difference between the practice of science and the salesmanship of science. For the former, failure is a critical component!

This month, in Nature, Melanie Stefan wrote an excellent piece on how individual scientists should emphasize their failures, a practice which I myself have put into play in my own CV!

I embrace failure! And Blue Brain will fail! And then we scientists will address those failures, highlight and repair the faults, embrace the successes, and iterate forward. And future Blue Brain may very well succeed!

But that's not my issue.

My main issue is the salesmanship. The grantsmanship. On their own site, Blue Brain claims that it is, "A Novel Tool for Drug Discovery for Brain Disorders" that will, "...provide a concrete foundation to explore the cellular and synaptic bases of a wide spectrum of neurological and psychiatric diseases."

This is called "over-hyping", and it happens all the time. Of course, this isn't a problem just with Blue Brain, or even in science. Anyone who has interviewed someone for a job, been on a date, or basically lived in the western world will be quite familiar with this phenomenon.

But, when it comes to science especially, over-hyping needs to be reigned in. It's a problem that is endemic to the very system in which modern science operates.

Now the new hotness is "connectomics", a research path for which I am a very strong advocate! As my friend Josh says, neuroanatomy is the RULES! If you don't know the anatomy then you can't say much about the brain!

Bradley Voytek human connectome project


Well, this week, Nature Neuroscience takes the over-hyping of the Human Connectom Project to task. (By the way, tons of love for the Nature Publishing Group in this post, apparently. Of course, being NPG, all of their links will be paywalled and thus inaccessible to many readers... ::sigh::)

Anyway, the piece, "A critical look at connectomics", astutely points out that,

Local connections in brain regions, which are roughly 80% of the connections in the cerebral cortex, are invisible to [current] imaging methods. Thus... the Human Connectome Project will necessarily provide us with partial and probabilistic data.

This is similar to the issue with the Blue Brain Project wherein they're currently (I believe) only modeling neocortical columns (for now). This represents fewer than half of the neurons in the human brain, fewer than 5% of the total cells in the brain, and who knows what portion of cognition (if it even makes sense to talk about "cognition" outside of a full brain). Of course, given my love for subcortical brain regions (see my PNAS paper), I'm a bit biased, but non-cortical brain areas really can't be ignored when you're talking about understanding brain disorders!

The editors at Nature Neuroscience go on to say,

It's tempting to sell the Human Connectome Project, and connectomics in general, as directly relevant to disease, particularly given the public money invested. However, given the challenges that this field is facing, it seems ill-advised to present connectomics as providing immediate answers for disease when it is clear that this is a long-term goal that will require the continued support and collaboration of the neuroscience community and the tax-paying public.

To translate: as scientists, the hyping that we do to get grants commits us to a message that may very well be detrimental to the very scientific endeavors that we love so much that we've dedicated our lives to pursuing them. Blue Brain does this. I've done this. Anyone who's written a grant has done this. And we need to stop.

So this post is to affirm my commitment to reigning in the hype. We can be exciting and relevant, without blowing smoke up the public's ass.

[EDIT: A friend pointed out to me that this post is similar in concept to Feynman's "cargo cult science" idea. While I wasn't consciously aware of this prior to writing this post, I still feel compelled to point that out in case I was unconsciously building off of it. Plus, Feynman is awesome and I love that phrase now and will be using it often, I'm sure, much to the annoyance of my wife, friends, and colleagues.]

22.11.10

Literary neuroscience: “Unseeing” in China Miéville’s The City & The City

As everyone is well aware by now, last month was quite the zombie neuroscience month for me. There was zomBcon, my interview of George Romero, and the National Geographic special, "The Truth Behind Zombies".

Well, I don't want to be a one-trick zombie pony. So I'm branching out with the whole neuroscience and science-fiction thing.

A few weeks ago my friend and colleague Roby Duncan told me that he was submitting an abstract to the 32nd annual International Conference on the Fantastic in the Arts in Orlando, Florida. He told me this the day before the deadline while I was at the annual Society for Neuroscience conference in San Diego. Yeah; I was working on a tight schedule...

Yesterday, I found out that my abstract was accepted! Thus, I will have 20 minutes to "read my paper" at the conference in March. That last bit is in quotation marks because that's a social science/humanities phrase that I think means give a talk, but I'm honestly not quite sure and I need to sort that out. This is my first non-scientific conference presentation. It should be an interesting conference. After nearly a decade of scientific conferences, I'm curious to see how the other half of academia approaches things. I expect about the same: with beer.

Anyway, for those interested, I'll be talking about China Miéville’s book, The City & The City, and the unique perceptual/awareness habits of its citizens. It's an excellent book, and Miéville is one of the best contemporary science-fiction/fantasy writers, in my opinion. The full abstract, as accepted, is below.

Breach in the mind: The hypothetical neuroanatomy subserving the process of “unseeing” in China Miéville’s The City & The City

In China Miéville’s The City & The City, citizens of the grosstopically overlapping cities of Besźel and Ul Qoma are taught from birth to “unsee” the architecture, people, events, and surroundings of the other city. Despite the terminology, unseeing is not just limited to the sense of vision, but to all other senses as well, and as such citizens must also “unhear” and “unsmell” stimuli from the other city. The consequences of failing to unsee are dire and possibly life threatening, as the semi-mystical force of “Breach” is charged with removing any offenders who willfully or accidentally notice the other city. In areas where the cities are cross-hatched, citizens of each city must carefully and selectively unsee their surroundings, even for houses neighboring theirs, for cars sharing the same roads, and for people walking the same streets. All the while they must unsee while noticing just enough to avoid running into their forbidden neighbors.

Although Miéville uses the process of unseeing for great narrative effect in a fictional setting, there is a rich neuroscientific literature surrounding the neuroanatomical bases for attention and awareness, perception, directed forgetting, sensory adaptation, repetition suppression, and other associated processes. In this presentation I will provide an introductory discussion on the neuroanatomical basis of attention and perception. From that foundation I will then provide a “hypothetical neuroanatomy” of what the brain of a person raised in a culture of unseeing might look like such that they could consciously and willfully unsee.

According to ironic process theory, the human brain fares quite poorly at avoiding certain thoughts when deliberately trying to suppress them. Thus I propose that a Besz or Ul Qoman citizen’s brain must develop differently when raised in an unseeing society to allow for such directed forgetting. Such goal-directed behaviors are mediated by an area at the front of the human brain known as the prefrontal cortex. The prefrontal cortex exerts control over sensory processes during normal perception, memory, and cognition. This process is referred to as “top-down” control.

I incorporate into my hypothetical neuroanatomy information from literature on patients with focal brain lesions, from neuroimaging, and from neural development to provide a hypothetical account for unseeing. Specifically, I will cite evidence from the brain lesion literature that shows that damage to specific brain regions affects the ability to attend to, remember, or be aware of certain stimuli, as well as brain imaging studies on attentional “blinks” and the role of ongoing brain activity in awareness, perception, and memory. Finally, I will discuss the physiological mechanisms behind sensory adaptation and how such mechanisms may subserve unseeing.

This science-nonfiction evidence can provide an understanding of the science-fiction of the Besz and Ul Qoman brain. I believe that the neuroanatomical plausibility of Miéville’s unseeing is what lends such strong credibility and interest to the story itself, as his narrative device of unseeing remains fantastic enough to differentiate from the real while being grounded enough in fact to remain comprehensible and relatable.

18.11.10

Updating university education

There was a question over on Quora a while back: "Will lecture-style teaching at universities become obsolete? If so, what do you think will replace lectures?"

I gave a somewhat off-the-cuff answer based on some thought processes that had been kicking around in the back of my head for a while. I'm curious to hear what people think.

From a purely cost-benefit point of view, it always struck me as wastefully redundant to have college professors and lecturers, many of whom are sub-par teachers but whom may be excellent researchers, teaching the same basic math, literature, biology, physics, chemistry, etc. courses. There are more than 4000 colleges in the US alone. At 10 hours of work per week of lecturing, prep, grading, etc., that’s more than 1 million hours per year in redundant work by highly trained specialists. Per course.

Why are we having a bunch of people who are trained to do research (and often not trained to teach), teach the same redundant information that takes time away from their research? Why not just broadcast lectures by the best of the best via some education syndication to consolidate the actual lecturing and have other professors and lecturers on-hand to supplement the information?

That said, homogeneity of education strikes me as a less-than-ideal solution...

12.11.10

zomBcon interview with George Romero: fast vs. slow zombies

Bradley Voytek fast vs. slow zombies


Some videos are now online!

As I mentioned previously, at this year's first annual zomBcon, much to my surprise, I found myself moderating and leading a panel with George Romero.

Ostensibly, the panel was meant to consist of George, myself, and two other panelists. The topic of conversation was slated as "fast vs. slow zombies". If you're unfamiliar with this terminology, the fast/slow zombie issue is a big one in zombie cinema.

The original Romero zombies (or, as he calls them, the "living dead") from his Night of the Living Dead were very slow moving. As he explained, this is because... well... they were dead. Rigor mortis and all. Of course they would be slow.

For many, the draw to the zombie genre is the very fact that no one zombie is necessarily scary. They're easy to kill, easy to outrun, and easy to outwit. The horror in zombie movies are the sheer numbers involved. There are hundreds, if not thousands of these dumb, slow moving, relentless creatures that have no desire and no will, just the need to feed. National Geographic's The Truth Behind Zombies (with yours truly!) goes into all of this stuff in some detail.

Now, in 1985, Dan O'Bannon (writer on Alien and Heavy Metal, effects specialist for Star Wars) made Return of the Living Dead. This somewhat horror, somewhat (now) comedy introduced the slightly more intelligent, faster, more coordinated zombie. While this movie is often most famous for Linnea Quigley's dance scene (googling this is NSFW), it also co-stars MST3K favorite, Clu Gulager (Clu Gulager alert!).

Back to the panel. What ended up happening was that George showed up a bit late while a few hundred people waited and I paced around up front. The other panelists never arrived, so it was just me on stage with Mr. Zombie himself. In the end I pulled up the rest of the zombie "brain trust" to help me out: Tim Verstynen and Steve Schlozman. We talked a bit about zombie neuroscience, video games, cinema, etc. It was very informal, and a lot of fun.

Looks like someone filmed the whole thing, too! The audio quality isn't great, but if you turn up the volume you can hear it decently well.

Here's the first video:



along with parts two, three, four, and five.

11.11.10

Voytek Frontiers in Human Neuroscience paper: "Shifts in gamma phase-amplitude coupling frequency from theta to alpha over posterior cortex during visual tasks"

This post is about my latest paper published in the (open access!) journal Frontiers in Human Neuroscience. This paper was actually an invited submission (even though it was invited, it was still peer-reviewed!) It was part of a special topic issue, "Origins and consequences of rhythmic cortical activity".

The Frontiers journals are, simply put, amazing. For those of you unfamiliar with the peer-review process, Penny Arcade sums up the experience pretty nicely (satirized here).

In all seriousness, here's how it works:

1. As a reviewer you often see the names of every author of the paper you're reviewing, but you never get to know who your reviewers are. The counter argument against changing this and making the system double-blind is often that, "people can often tell who wrote a paper anyway based upon the content, methods, etc."

To deal with this, the Frontiers journals start off single-blind, but after all the reviews are completed the reviewers are unblinded and everyone knows who everyone is. This has lead to substantially nicer, more helpful reviews, in my opinion. All reviewer names are published along with the paper which means that the reviewers are held somewhat publicly responsible as well.

2. Speed and nature of communication. Reviewers often take weeks or months to review a paper. And then the author takes several weeks to respond. And then the reviewers go back and review the responses, etc. This can lead to a several-months long review process. Again, the Frontiers journals have addressed this nicely. After the first round of reviews the editor initiates an interactive online forum where the editor, reviewers, and authors can interact at a more rapid pace.

3. Editors and "novelty". Often papers get rejected before ever being reviewed because an editor deems the paper to be not "novel" enough to warrant publication in their journal. This tends to be a problem for the "high impact" journals. The Public Library of Science has addressed this by introducing PLoS ONE, which publishes nearly any paper deemed scientifically and methodologically sound, regardless of "novelty".

So the review process was actually quite interesting and quick. It's nice to see some publishers embracing technology a bit and allowing for rapid, forum-style communication between the authors and reviewers.

As for the paper itself, the idea grew out of a pretty simple follow-up based on an awesome paper by my friend, colleague, groomsman, and co-author, Ryan Canolty. In 2006, Ryan published a paper in Science: "High gamma power is phase-locked to theta oscillations in human neocortex". As the title implies, they found that oscillations in the human neocortex form nested rhythms across frequency bands. They showed that the phase (how "peak-like" or "trough-like" the sinusoid is) of low frequency "theta band" activity (4-8Hz) modulates the amplitude of high frequency "gamma band" activity (80-150Hz).

Bradley Voytek Frontiers in Human Neuroscience 2010 Shifts in gamma phase-amplitude coupling frequency from theta to alpha over posterior cortex during visual tasks


More simply: when the theta wave is at its lowest point, the trough, power in the gamma band is highest. You can see a toy example of this in the image above.

Great! But why do we care?

First, gamma band power correlates with single-unit (neuronal) spiking activity correlates with fMRI BOLD signal. That is, all of these different signals that we measure might be a way at getting at neuronal activity more directly.

Second, oscillations in low frequency rhythms are probably reflecting (sub-threshold) changes in the extracellular membrane potential. For neurons to "fire" an action potential, ion channels in the cells themselves must open to allow ions (and thus charge) to flow.

Third, low frequency oscillations may help coordinate long-distance communication between brain regions by "shaping" which neuron groups are more likely to respond to a stimulus by biasing the statistical probability of action potentials occurring. Thus, these nested brain rhythms might reflect a mechanism of connecting single-unit activity with huge brain networks, and may reflect the way that the brain "works".

That was really dense. Let's unpack that.

We don't know how different brain areas communicate to give rise to cognition. There's a complicated code that we don't understand. This nested oscillations idea might connect the really low-level physiology of the brain with high-level cognition that requires communication between a lot of brain regions. And it ties it all nicely together into a cool communication system where different low frequencies could act as "switches" to bias information flow between brain regions.

I've talked about oscillations here before: in my post about the paper "Endogenous Electric Fields May Guide Neocortical Network Activity", in my post on neuroimaging, "What can we measure using neuroimaging techniques?", and in the post about my paper in the Journal of Cognitive Neuroscience, "Hemicraniectomy: A new model for human electrophysiology with high spatio-temporal resolution".

In this paper we recorded data from two human patients with implanted subdural electrodes. This technique—known alternately as "electrocorticography" (ECoG), "intracranial EEG" (iEEG), or "intra-cranial electrophysiology" (ICE)—is a surgical procedure done as a treatment for (usually) epilepsy. I've talked about this stuff before (see the above links); it's a staple of my research. (For a more detailed explanation as to why someone might get electrodes surgically implanted into their brains, check out this part of one of my talks).

The first step was to recreate Ryan's findings that gamma amplitude couples to theta phase.

Bradley Voytek Frontiers in Human Neuroscience 2010 Shifts in gamma phase-amplitude coupling frequency from theta to alpha over posterior cortex during visual tasks. Theta gamma phase-amplitude cross-frequency coupling


When we recreate the conditions of Ryan's experiments (auditory tasks, frontal electrodes) we see really nice theta/gamma coupling, as can be seen in the image above. When the subjects are performing non-visual tasks, theta/gamma coupling is strong across most electrodes. The more red the electrode, the strong the theta/gamma coupling. In the comodulogram (colorful thingy on the left) you can see the average theta wave in the specific highlighted electrode. You can also see the red stripes above it that occur during the trough of the theta. The more red those stripes, the higher the gamma amplitude. Nice coupling.

Bradley Voytek Frontiers in Human Neuroscience 2010 Shifts in gamma phase-amplitude coupling frequency from theta to alpha over posterior cortex during visual tasks. Alpha gamma phase-amplitude cross-frequency coupling


Now, in contrast, when the subjects perform visual tasks, we see that at electrodes over the posterior (visual) parts of the brain begin to exhibit coupling between gamma power and a different low-frequency band; alpha. Alpha is a "visual" brain rhythm that is strongly modulated by visual attention. When subjects are visually engaged, we find that phase-amplitude coupling over the posterior cortex shifts to an alpha/gamma pairing.

This paper is the first time anyone has shown that the phase frequency in phase-amplitude coupling is selectively modulated by behavioral state.

Good times!

This work was financially supported by the (sadly defunct) American Psychological Association Diversity Program in Neuroscience grant 5-T32-MH18882 (to B.V.) and the National Institute of Neurological Disorders and Stroke grants NS21135, NS21135-22S1, and PO40813 (to B.V. and R.T.K.).

Voytek B, Canolty RT, Shestyuk A, Crone N, Parvizi J, and Knight RT (2010). Shifts in gamma phase-amplitude coupling frequency from theta to alpha over posterior cortex during visual tasks. Front Hum Neurosci.