darb.ketyov.com

Caveat lector: This blog is where I try out new ideas. I will often be wrong, but that's the point.

Home | Personal | Entertainment | Professional | Publications | Blog

Search Archive

Loading...

26.10.10

Zombie neuroscience

So a lot of folks have been wondering what's going on with the zombie neuroscience thing. Let me explain.

I was first approached about working on a zombie neuroscience project over the summer. Matt Mogk runs the Zombie Research Society (ZRS), which is a website he started because he’s a zombie lover. And, as he said, "Zombie Research Society" sounds more cool than "Matt’s Zombie Blog".

So Matt had seen my TEDxBerkeley talk wherein I began by saying that one of the reasons that I was really motivated to get into science (in general) and neuroscience (specifically) were really geeky things: comics, video games, sci-fi, etc. So Matt was looking for someone who could talk brains and who loved zombies. He cold emailed me asking me if I was into zombie movies, and there you have it. My wife and I are huge zombie fans. We both read World War Z and The Walking Dead and have watched dozens of zombie flicks. We even mused about starting a searchable online zombie movie database.

Anyway, so Matt had already hooked up with Dr. Steven Schlozman from Harvard, who made a little splash when he gave a grand rounds presentation on the neurobiology of zombism. Matt was looking for more. So we talked about some fun projects we could do together. I was a bit skeptical at first and—since I was just starting out with my new post-doc—a bit too busy to tackle all of this myself. So I called up my colleague, friend, and fellow zombie enthusiast Dr. Timothy Verstynen to see if he wanted to collaborate on some fun zombie stuff. After explaining the project, he was totally on board.

So Matt put us on the ZRS advisory board and Tim and I started working on a fake paper about the zombie brain.

But why, you ask? Partly because it’s a great way to talk about some really complicated neuroscience stuff in a way that engages the public’s interest. If you start talking about the subtleties of how neuroimaging and lesion research shed light on how different brain regions interact to give rise to complex... zzzzZZZZZZzzz. Right? I mean, I care a lot about this stuff, but if you talk about how brain regions could interact to give rise to a ZOMBIE, suddenly normal people are interested, too.

We decided right from the start that all the neuro stuff we would talk about would be 100% true (except for the fact that there could be a zombie, of course).

We wanted to trick people into learning about neuroscience.

The other reason I wanted to do this was, well... for the lolz. The entire time I’m doing this I can poke fun at myself and my field. We have a tendency to narrowly describe some brain function, find some behavioral and neuroimaging correlation, and then act as though that explains the brain. Our work is way more complicated than that. So by using something as overly ridiculous as zombies and breaking down their symptoms and classifying their "disorder", I can make a little tongue-in-cheek commentary about my own field. I don't ever want to take myself too seriously.

That said, this has blown up pretty quickly. I was already interviewed by National Geographic for a special they did called "The Truth Behind Zombies".

Look at this. This is what I looked like when they filmed me. I happened to be in LA while the English NatGeo film crew was in town to film Max Brooks. I'm dressed for a wedding! Ridiculous. I never wear a button-down shirt.

Bradley Voytek neuroscientist NatGeo National Geographic The Truth Behind Zombies


And I haven't seen the show yet. I have no idea how it went. We'll see. I tried to explain why I'm doing this, but hell, for all I know I'm going to be edited down to saying, "PFC damage will make you a zombie."

I mean, that's my biggest concern about all of this. I care a lot about my research, and I care personally about the patients with whom I work. I don't want anything I'm doing to be seen as making light of them when what I'm really trying to do is poke fun of myself and my fellow neuroscientists, have fun while doing it, and maybe get people to accidentally enjoy science along the way.

And finally, honestly, the inner geek in me is stupid excited that a) anyone cares about the information I've worked for so long to obtain and that b) I get to meet friggin' George Romero, the father of zombie movies!, Bruce freakin' Campbell, Malcolm McDowell, Chuck Palahniuk, and Max Brooks. Just being referenced on the same page as them is awesome! I'm not star-struck; I'm geek-struck.

7.10.10

Fraud in science: What's in a name?

Bradley Voytek Hello my name is


So everyone's all atwitter about this NYT article, "Rampant Fraud Threat to China’s Brisk Ascent".

I find it interesting that no one's been mentioning the feature in Nature a few years back about China's "identity crisis".

The NYT piece highlights a lot of issues in scientific (mis)conduct, but the Nature feature was far more fascinating in terms of how scientists can game the flaws in the scientific publishing industry.

In the Metafilter thread on the Nature piece, one of the commentors linked to a few news articles about Chinese names. According to Xinhua:

Only 4,100 different Chinese surnames have been found to exist out of a sample of 300 million Chinese people, according to a survey by the Chinese Academy of Sciences (CAS).

This issue is apparently quite problematic for law enforcement and, according to Rueters, the Chinese police have been considering alternatives to traditional naming conventions:

At least 100,000 people share the name "Wang Tao", the China Daily said, citing the Chinese Academy of Social Sciences... China has 1,601 surnames in total. According to the new regulations, Arab numbers, foreign languages and symbols that do not belong to Chinese minority languages would all be banned.

But, as Nature pointed out, this isn't just a law enforcement issue, it's also an easy way to commit academic fraud.

Jia Wei, associate dean at the pharmacy school of Shanghai Jiao Tong University can remember hundreds of metabolic pathways by heart, but he gets confused by his graduate students' publications. Three of his students—Wang Xiao-yan, Wang Xiao-rong and Wang Xiao-xue... have completely different two-character given names in Chinese, but all publish under the abbreviated name X. Wang. “I really have a hard time sorting out who has published what,” Jia sighs.

After setting an establishing example for the problem, they continue:

The [naming] problem is sufficiently widespread that some researchers have taken advantage of the ambiguity. Surgeon Liu Hui, who padded his CV with publications by another researcher who shared his surname and initial, rose to become an assistant dean at the prestigious Tsinghua University. But the discrepancies were noticed and he was dismissed by the university in March 2006.

As science becomes less WEIRD and more globalized these kinds of issues become more problematic.

In south India, women may not have surnames and are forced to adopt them to publish in science (with this caveat):

Indians from the south traditionally do not have surnames. It is only when forced to comply with Western naming standards that they use their father's given name as a substitute. As a consequence, journal rules require them to publish research under the fathers' given names (with which we—Nalini, Jeevananthinee and Sujatha—also sign this Correspondence letter). Obviously, as young south Indian scientists making a contribution to science, we would prefer to be identified with our first names and not by our fathers' given names.

Naming issues also affect citation rankings.

On the one hand, it surprises me that a technological solution hasn't been widely instantiated to address this. On the other, this is obviously a complex issue and getting a wide array of publishers, databases, etc. all to cooperate and adopt the same standards would be a ridiculously impossible job. As my wife would tell me, database standards are not quick to get adopted. People are slow to change.

EDIT: Note my wife's comment (and correction to my assumption about what she would say) below.

5.10.10

Voytek PNAS paper: "Prefrontal cortex and basal ganglia contributions to visual working memory"

This post is a detailed breakdown of my most recent (open access!) article in PNAS, Prefrontal cortex and basal ganglia contributions to visual working memory.

The official press release from Berkeley for this paper won't be out for a while, as it's being wrapped into a larger story with my also-accepted paper to Neuron, Dynamic neuroplasticity after human prefrontal cortex damage. Both the PNAS and Neuron papers are experiments where I worked with people who had stokes. This PNAS paper shows how very specific strokes to different parts of the frontal lobes affect working memory. The Neuron paper looks into how different brain regions pick up the slack for the damaged parts of the brain.

In the meantime, since the PNAS paper is online already, I've decided to publish my thoughts on it.

Bradley Voytek PNAS 2010 Prefrontal cortex and basal ganglia contributions to visual working memory


I believe a lot of my blog readers are here via MindHacks or my twitter because of the strange neuroscience historical pieces I've written about self-experimentation, sperm injections, psychic powers, and scientific pharmacological aides. What a lot of you don't know is that I'm trying to pretend to be a for reals scientist, too!

When I first started this blog, I was finishing up my PhD thesis at Berkeley. At the time of my graduation I had three papers out in peer-review, a process that totally destroys all sense of self-worth in a young researcher.

Anyway, the good news is, that this paper was almost a pleasure to have go through the peer-review process. The journal that published my work, PNAS (The Proceedings of the National Academy of Sciences, USA), used to be infamous for its policy wherein researchers who were members of the National Academy of Sciences could "fast-track" their papers into the journal, even by-passing peer-review altogether! Well, since their announcement that this will no longer be done I've become a much bigger fan! Needless to say, I'm quite proud and honored to have my paper accepted there. And now that the media embargo is lifted I can finally talk about it here.

This is my first major research publication that was directly related to the topic of my PhD thesis, "Frontal and Basal Ganglia Contributions to Memory and Attention".

As I said in one of my first posts, "if the public is paying for my research, at the very least they should be able to know what was done and why I thought it was worth doing." To that end, I've tried to do a lot of communicating my research such a giving public lectures (e.g., TEDxBerkeley, Google). I'm also making it a point to write about my peer-reviewed publications. My first scientific write-up was on my hemicraniectomy paper, "Hemicraniectomy: A new model for human electrophysiology with high spatio-temporal resolution" in the Journal of Cognitive Neuroscience (full, free paper here).

Technically this paper was pretty challenging; it's not as mathematically challenging as some of my other work (e.g., "Shifts in gamma phase-amplitude coupling frequency from theta to alpha over posterior cortex during visual tasks"; post coming soon!) It was, however, methodologically more complex. As my PhD advisor and coauthor, Robert Knight, and I said in our letter to the editor when submitting the paper, "[o]ur manuscript provides the first evidence combining human electrophysiology, psychophysics, and focal brain lesions to clarify the role of cortical and subcortical frontal regions in working memory."

To unpack that a bit, we worked with two groups of patients who had strokes. We screened a lot of brain scans prior to the research to look for people who had relatively focal brain lesions in very specific areas of the brain. Because the extent of damage caused by any given stroke is highly variable, it was difficult to identify a group of subjects. Specifically, I was interested in people who had damage only in one hemisphere of the brain, to either the prefrontal cortex (PFC) or to the basal ganglia (BG). The reason for this is that, while decades of previous research has shown that the PFC is important for working memory, only for the last decade or so have people really been looking at the BG as important in cognitive functions.

Or, as we said in science-speak, "[a]lthough the basal ganglia and prefrontal cortex are known to be associated with working memory processes, the precise anatomical and functional roles they play have not been causally demonstrated in humans." I'm very interested in how different brain networks work together in complex cognition, so working with these patients gives a rare opportunity in cognitive neuroscience to look at more causal questions; that is, what brain areas are needed for cognition, not just what brain areas are correlated with it.

The figure at the top of this post shows the average of the two patient groups where the color represents the number of patients with a lesion in that exact brain area.

We chose to study working memory for a variety of reasons. First, philosophically, as I say in the paper, "[v]isual working memory (VWM) is a remarkable skill dependent on the brain’s ability to construct and hold an internal representation of the world for later comparison to an external stimulus." That right there strikes me as an absolutely amazing skill that we have. Second, it's a natural extension of some of the work out of my advisor's lab that showed that, in patients with unilateral PFC lesions, their attention abilities are intact when you present a visual stimulus to their "good" half of their brain, but they're a little worse when you present it to the "bad" half of the brain. Vision, by the way, is lateralized just like movement. Most people know that the right half of your brain controls the left half of your body (and vice versa). Well, the left half of your visual world (not the left eye, but the left half of space) is processed by the right half of your brain. So anyway, these patients with PFC lesions have worse attention when the thing they need to pay attention to is presented to the damaged half of the brain.

What's neat about that Francisco Barceló Nature Neuroscience paper was that they used scalp EEG to show that PFC lesions actually affect the way the visual cortex processes information within the first 100-200 milliseconds. This is called a deficit in top-down processing, because the PFC, a "cognitive" region of the brain (at the "top" of the cognitive ladder) is assisting the visual cortex, a brain region "lower" on the cognitive ladder.

So we wanted to use EEG in our experiment to show that what Barceló showed in PFC patients for attention would be the same for working memory. One of my collaborators, Ed Vogel, had a cool Nature paper where he showed that EEG over visual cortex could actually be used to predict an individual person's working memory capacity with decent accuracy.

But I wanted to extend this idea even further. Another colleague of mine, Earl Miller, had a Nature paper a few years back where they showed that a small, subcortical region in the frontal lobes, the BG, might actually be training the PFC in certain kinds of learning tasks. That, along with a lot of other evidence, supports this "network" idea of brain functioning where different brain regions have to act in concert to give rise to complicated behaviors.

Like I said earlier, working with patients with brain lesions is one of the few methods we have in cognitive neuroscience to get at some questions of causality. You can stick 1000 people into an fMRI machine and show that blood flow increases in some brain region in response to a task, but you still can't say that that brain regions is doing the task. All it takes is one person with a lesion to that region who can still do that task to disprove causal statements in the brain imaging literature.

So we went into this experiment with the idea that, even though PFC lesions tend to be much larger than BG lesions, because of where the BG sit in anatomical relationship to the PFC and the rest of the brain, we hypothesized that patients with the (smaller) BG lesions would do worse at the task.

Bradley Voytek PNAS 2010 Prefrontal cortex and basal ganglia contributions to visual working memory


As you can (maybe) see in the figure above (part C), that's just what we found. Like the Barceló study, we show that patients with PFC lesions are fine when the stimuli enter the "good" half of the brain, but are worse (compared to healthy control subjects) when they enter the "bad" half of the brain. These deficits are both attentional and working memory in nature. In contrast, patients with BG lesions do worse regardless of which hemisphere the visual information enters, but this is specifically a working memory deficit; attention is intact. Especially interesting to me is that the BG patients do extra worse during the first 25 trials or so, which suggests a learning deficit, too.

Okay, so this post is getting really long, so I'll spare all the intricate details, but there's one neat point in the paper that we had to put into the supplemental materials that I really liked. One of the reviewers asked about a piece of our data that I thought was interesting and intriguing as well, so we dug into it a little more. Basically, there was a great PNAS study where (yet another colleague of mine) Ole Jensen showed that brain oscillations may actually be generating those EEG signals that Vogel showed to predict memory capacity.

Bradley Voytek PNAS 2010 Prefrontal cortex and basal ganglia contributions to visual working memory


Since I'm an "oscillations" guy, I really dug this work. So we looked at those same oscillations and found that patients have larger alpha oscillations over the damaged hemisphere (as can be seen in the above figure), specifically over the visual cortex. The more abnormal their alpha was, the less predictive of memory load their EEG was. We interpret this as a loss of top-down facilitation of visual attention/working memory. This latter point is super cool, and one I'd like to investigate in future experiments.

Anyway, take home messages:

1. Networks: important!
2. Basal ganglia: cognitive!
3. Alpha: interesting!

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 and Knight RT (2010). Prefrontal cortex and basal ganglia contributions to visual working memory. Proc Natl Acad Sci USA.

4.10.10

Positron Emission Tomography (PET) is a dirty business

Prior to starting my PhD at Berkeley I worked at the UCLA Brain Mapping Center (which really needs a new website!) as the PET scanner operator. That was awesome! But wow were there some items that were not in the job description... good and bad.

Bradley Voytek Bill Nye


Good: yeah, that's me "scanning" Bill Nye the Science Guy for the "adult" version of his kid's TV show, which was named The Eyes of Nye. He was doing an episode on drugs and drug abuse. Since that's what my boss (and by extension, I) was studying at the time, he came and did part of his show in our lab.

I started working at UCLA a few months after finishing up my undergraduate work at USC. As I've talked about a bit, I was a downright awful student as an undergraduate. Terrible. Like, kicked-out-of-school bad. So when I decided I wanted to pursue a career in academia, I knew I needed some research experience to overcome my crap GPA.

When I got the job at UCLA, I was pretty excited about being able to work on my own side-projects! Ultimately I got one first-authored manuscript (Differences in regional brain metabolism associated with marijuana abuse in methamphetamine abusers) and two others (here and here) out of my two years in the lab.

All of these papers used PET and involved former methamphetamine abusers, but those weren't the only people we scanned. Because I was the primary PET scanner, I worked with many collaborators including Sanajaya Saxena (who was Jack Nicholson's psychiatric consultant for OCD in As Good As It Gets).

That's what happens when you're a scientist in LA: you work with TV and movie stars all the time. It's not just all the waiters and baristas that are actors; all the scientists are, too!

Now, here's how PET works: a radioactive substance is put into the body—either through ingestion, inhalation, or injection—where the specific radioligand determines the pattern of uptake. To study brain function, the radiotracer we used was F18 fluorodeoxyglucose (FDG). This is effectively a radioactive version of glucose, which is a very important "fuel" for the brain. Regions of the brain that are "working harder" require more fuel, and thus more radioactive glucose is more concentrated in them. The PET scanner detects the relative density of the radioactive glucose in the brain, and thus can be used to build a 3D statistical representation of neural activity distributions.

Bradley Voytek Synapse 2005 Differences in regional brain metabolism associated with marijuana abuse in methamphetamine abusers


Here is an example from my only first-author PET paper showing that long-term marijuana users who are also methamphetamine abusers show lower glucose metabolism in temporal lobe and basal ganglia regions compared to methamphetamine-only abusers.

Now those of you paying attention may think, "but gee, you're injecting radioactive substances into the body, isn't that dangerous?!" "Noooooo, not at the doses used in our experiments", I would say! 75% of the radioactivity has decayed within 2 hours of production, which gave us narrow time-windows for research. I would pick up the FDG at the cyclotron, walk it back over to the PET scanner (shielded in a very heavy lead container), and start the experiments.

However, FDG is cleared through the body largely via the bladder. Thus, if we had subjects pee after our study, we could lower the radioactive dose further. Even though the doses are low, getting them lower is always better.

Now, did you catch that?

We can lower the radioactive dose by having subjects pee.

Pee. RADIOACTIVE PEE.

Here's the part that wasn't in the job description:

Part of my job was to grab my Geiger counter, put on my gloves, grab my radioactive spill cleaner, and head into the bathroom after our subjects peed. Then I got to scan the entire bathroom and scrub up any "hot spots" (spilled radioactive pee).

Guys suck at peeing. We splash everywhere. I know this as a verifiable scientific fact now.

And now you all know my futuristic, radioactive neuro-janitorial story.