What caused this all-to-confusing issue? One scientific paper. This paper, published in The Lancet in 1998 and then fully retracted in 2010, revealed results linking autism to vaccines in 12 children. This paper was riddled with undisclosed conflicts of interest, falsified data, and irreplicable results. In fact, the lead author of the paper lost his medical license following an in-depth investigation of this paper.
Since the release of this paper, countless studies have been conducted to explore the potential autism-vaccines link. No data has yet to support this link. In addition, the US has established a specific system, often called the Vaccine Court, to litigate claims related to vaccines and autism. 5,000 cases have been reviewed or are currently in process and, to date, only one has been shown to demonstrate a link between vaccines and a specific type of brain inflammation (which is not autism).
What's the problem here? Of course, there is a problem with the scientist who fraudulently published the 1998 paper. But, there lies a potentially greater problem in listening to him. This controversy has led to dramatic decreases in the rates of parents vaccinating their kids. Accordingly, there have been increasing incidences of preventable diseases, like polio and whooping cough. What's interesting is that there has also been an increase in the incidence of autism, with the latest US estimates at 1 in 88. Clearly, something else is causing this disorder.
What are the solutions? Ending this debate doesn't fall solely into the laps of parents. Yes, children need to be vaccinated and parents should stop lobbying against vaccines. But, autism researchers need to better communicate the truth about vaccines and autism. They need explain more of their scientific findings to the general public. The vaccine vacillation is just one of many confusing chapters in the book of autism. Scientists need to start writing in this book with a lay-oriented hand, and the public needs to keep reading it.
Photo source: http://www.stockfreeimages.com/
Think back two posts ago. I mentioned how some everyday experiences can cause stress reactions in people with autism. Add eye contact to that list. Several studies have shown that direct eye gaze from others can bring on physiological signs of stress in those with autism. Again, here's where our lab's research comes to bat. In a recently completed study, we hypothesized that by blocking the stress response system in people with autism, eye contact may be become more easy. Just as in the other study, we used propranolol, a drug designed to block receptors in the brain that are a part of the stress response system.
In this study, we examined eye contact via a machine that tracks the location of eye gaze. This machine, called an eye tracker, can tell us where a participant is looking and how long they look there. To mimic the direct gaze of another person, we used video clips of people looking directly at the video camera. We had research participants with autism view 32 of these clips on two different study days. Just as before, we compared the effects of propranolol, given on one study day, versus placebo (a sugar pill), given on the other. Overall, we hoped to see a benefit of propranolol in improving eye contact, or increasing the time the participants spent looking at the eyes of the people in the video clips.
Here's the interesting part about science. 99.999% of the time, you don't find exactly what you expect. We did not see differences between propranolol and placebo in eye contact. However, we did find that propranolol significantly decreased the amount of time our participants spent looking at the people's mouths in the video clips. What does this mean? We are not entirely sure.
Is looking someone in the mouth an impairment linked to reduced eye contact or is it an adaptive strategy used to cope with the stress of eye contact? And how does the effect of propranolol on mouth gaze fit into the picture? As is common in the field of autism research, our findings produced more questions than answers. All the more reason to keep asking.
It's awkward. We do it because we have to, not because we like it. And did I mention, it's awkward?We're talking networking.
Yes, we normally cringe at the thought of another schmooze fest at the office, but when it comes to the brain, networking is not only important, but crucial. For any behavior or any cognitive process to occur, multiple areas of our brain must work in concert. These areas may be distant from each other in the brain, but become active at the same time or deactivate together. This pairing of activity may imply that the areas involved are necessary for whatever behavior is taking place. This is called functional connectivity. The areas are connected, not physically, but in terms of what they are used for.
Within the brain, there are countless functionally connected networks designed to carry out the processes of everyday life. What's surprising though is how we have networks that are active even when we are doing nothing at all, like when we sleep. These networks, called resting state networks, are the least understood. It's not quite clear what these networks are for. Furthermore, in the case of a mental disorder, such as schizophrenia, these resting state networks seem to be disrupted. They are less connected, or have weaker connections. Clearly, there some importance to these networks.
Here's where my project comes in. It has been shown that individuals with autism have less functional connectivity at resting state than those without autism. There might be disruptions in the resting state networks. But which networks and which areas are involved in this disruption? In my project, I am analyzing data from fMRI scans of individuals with autism and control participants without autism. During the scans, the participants were instructed to lie still in the scanner, thinking about nothing in particular for 5 minutes. With the data analysis technique I'm using, I'll be able to determine which of 90 areas in the brain are functionally connected when a participant is at rest. I'll also be able to visualize the resting state networks of the participants by constructing graphs of the functionally connected areas. With this, I hope to find differences between the autism group and the control group in the graphed networks. The differences may include changes in the strength of certain connections or even discrepancies in which areas are connected.
What's to be gained here? We already know that functional connectivity is decreased in autism. However, studies like this one will allow us to gain knowledge of the overall properties of the resting state networks of people with autism. Are their networks under-connected, over-connected, or completely different? To know these things will bring us closer to understanding the nature of this disorder, and more importantly, how we can better help.
The almost cliché concept, "fight-or-flight," is well-ingrained in our minds. Walking down a path, you suddenly realize that the stick you were headed toward is actually a snake. You are on Facebook at work and your boss appears out of thin air. Or, as a professor recently described, you are hiking in the woods and you come across a bear with a gun. Not just a bear. One with opposable thumbs and a firearm. Regardless of the event (no matter how implausible) the reaction is the same: your heart races, your palms sweat, and your breathing becomes rapid. Your body is preparing you either to roundhouse kick the gun from the bear's mutant-hand or to run away faster than Michael Johnson. What would it be like if this same reaction occurred when you tried to remember the list of grocery items you wanted to pick up? Or when an acquaintance starts a conversation with you?
According to several studies, these seemingly commonplace events are often quite stressful for people with autism, even stressful enough to bring on fight-or-flight symptoms. Behind these symptoms is a brain chemical called norepinephrine that runs the stress response system. Here's where our lab comes into the picture. We are hypothesizing that blocking the function of norepinephrine in the brain will reduce stress in people with autism, thus improving their cognitive and social abilities. To block norepinephrine, we are using a drug called propranolol, which is typically prescribed for hypertension or test anxiety. Propranolol works by blocking receptors in the brain that normally respond to norepinephrine.
In a current study, we are comparing the effect of propranolol to that of placebo (or a sugar-pill) on a range of cognitive and social tasks completed by participants who have autism. These tasks involve things like remembering and repeating back lists of words or choosing between two topics and participating in a short conversation (sound familiar?). Our hypothesis is that propranolol, by blocking the stress response, will improve performance on these tasks. If this turns out to be true, we will have identified a drug (that is already on the market and is relatively cheap) as a potential treatment for some core features of autism.
Let's be clear: propranolol is not and never will be a cure for autism. In fact it's quite likely that there never will be a cure, or even just one drug that solves everything. What we are trying to do is to improve the daily life of someone with autism. To allow him to handle the stressors of the everyday things a little more easily. To help her engage the world a little bit more. For me, that's an important enough goal as any.
If you don't know the famous Gilmore-ism that is the title of this post, STOP reading this and put Gilmore Girls on your Netflix queue. Now. You won't be sorry.
After you've taken care of that, I'd like to start my first series as part of Tuesday Thoughts. Yes, a series is the cure I've invented for an unexpected hiatus from blogging for 3 weeks. Here we go... This series will cover the projects I'm working on in lab. And, yes, it can be a series because I'm currently working on more projects than I can count on one hand. #too many
We'll start with my first solo project, which I'm clearly excited about because it gets to be first in the series. In this study, I am exploring the incidence of impaired social behavior in miniature and standard poodles. Clearly, a study as random-sounding as this deserves a little background:
My lab here at MU primarily studies autism spectrum disorders, which are a collection neurodevelopmental disorders characterized by the presence of impaired social abilities, communication deficits, and repetitive behaviors (think hand-flapping). My adviser is an MD, who sees patients in clinic who have autism. He also happens to be married to a former dog show handler. We're talking Westminster, Eukanuba, etc - the big leagues. Offhandedly, my adviser's wife mentioned some unique qualities she'd seen in some poodles: they displayed poor eye contact, they had difficulty communicating needs to their owner or handler, or they had strange habits that seemed repetitive. Wow. Does that sound familiar?
Now, it's important that I make myself clear. We are not saying that there are autistic poodles running around out there. But what we are saying is, "Hey, if there are some genetic differences between the autistic-like poodles and the non-autistic-like ones, we may be able to get one step closer in figuring out the genetic underpinnings of autism." This kind of thinking drives many aspects of animal model research. But what's so exciting is how much more similar we as humans are to dogs, rather than to mice or rats.
Well, are there genetic differences? Hopefully time will tell. Right now we are collecting data and waiting to hear if we got a grant that would allow us to do genetic analyses. What's unique about this project is the impact it could have if we find something interesting. We would not only contribute to autism research but also learn more about dog behavior and how to help dogs with social impairments. Everybody wins. Now who doesn't like that?
{Favorite thing #1}
I found the quote below from The Common Sense of Science by Jacob Bronowski on an autism research blog I follow. I just love it's pointed depiction of the lack of public communication ability among most scientists:
"[Scientists] have enjoyed acting the mysterious stranger, the powerful voice without emotion, the expert and the god. They have failed to make themselves comfortable in the talk of people on the street; no one taught them the knack, of course, but they were not keen to learn. And now they find the distance which they enjoyed has turned to distrust, and the awe has turned to fear; and people who are by no means fools really believe that we should be better off without science."
{Favorite thing #2}
I've been following the launch of Matter (http://www.kickstarter.com/projects/readmatter/matter) for several weeks. Matter is an upcoming journalism project that focuses on long-form reporting about science and technology. This publication will be one of the first to bring this type of in-depth, highly quality science journalism to the web. See the link for a video and information about the project.
{Favorite thing #3}
Thanks to Twitter, I was able to check out Brainfacts.org (http://www.brainfacts.org/) the day it launched. This website, developed in part by the Society for Neuroscience, is a brand new resource for the public to learn about all things brain. What is so great about this particular "public information initiative" is the source of its information. The editors to the site are all leading neuroscientists, making the information not only highly accurate, but up to date and relevant.
{Favorite thing #4}
I don't even remember how I found To Think, To Write, To Publish (http://www.thinkwritepublish.org/), but I'm glad I did. To Think, To Write, To Publish, is a workshop dedicated to advancing the publication communication of science in a unique way. Instead of handing a scientist a press release request or a journalist a microscope, this workshop pairs scientists and science writers, asking them to develop a creative non-fiction story together. With this approach, the stories produced and later published are (refreshingly) both informative and enjoyable to read.
Notes from a Post-it Junkie
thoughts on science, public communication, and surviving graduate school
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