SfN Day 2: Change in stress across development and functional connectivity

Day 2 has already been jam packed with lots of exciting findings presented here at Neuroscience 2013. In some weird, unintentional effort to wear myself out (what is wrong with me?) I’ve been going up and down the escalators, bouncing between the poster hall and talks all morning.

In one of my forays upstairs, I sat in on a short talk by Alice Graham from the University of Oregon. Graham presented a novel way to look at a commonly studied topic: early life stress. Citing a study that discovered obesity in individuals who experienced famine in utero as opposed to postnatally, Graham emphasized that there is a mismatch between pre- and postnatal environments when it comes to risk for disease. Instead of looking at stress at a specific time point in development (e.g. only prenatal), Graham proposed looking at the change in stress that occurs as an infant transitions from the pre- to postnatal environment.

This change in stress might be particularly evident in a variable such as interparental conflict. This variable, tested via response to an angry-toned voice, has been previously shown in Graham’s work to influence functional connectivity between the medial prefrontal cortex (mPFC) and other brain regions in infants. In a new study, Graham used self-report measures to show that interparental conflict is higher in the postnatal environment, meaning after a baby is born, as compared to the prenatal environment, meaning during pregnancy. Perhaps this has something to do with sleep deprivation and the screaming, spitting up bundle of joy, I’m not sure.

Since there is a difference in the stress due to interparental conflict that an infant might experience prenatally versus postnally, there may be differential effects of this stress on development. Graham studied this difference within the context of resting-state functional connectivity in the default mode network (DMN), a functional network in the brain that is active when someone is not specifically engaged in a task. Graham chose this network because it seems to be impacted by early life stress and it exhibits rapid development from 0 to 2 years of life.

When subtracting prenatal interparental conflict from postnatal interparental conflict, Graham showed that functional connectivity was increased between the posterior cingulate cortex and the following regions: mPFC, medial temporal lobe, inferior temporal gyrus, and the right amygdala. Thus, the postnatal increase in the stress an infant might experience due to interparental conflict seems to increase functional connectivity between several regions of the DMN, effectively speeding up the development of this network.

Perhaps this is an adaptive response to stress. However, Graham noted that another study has reported increased DMN functional connectivity in full term infants as compared to premature infants, meaning the less stressed, full term infants actually displayed greater DMN connectivity. This finding is in contrast to the findings of Graham’s group. Accordingly, further study of the effects of change in stress across development is necessary. Perhaps different types of stress have different effects at different times. As with most questions in neuroscience, this idea is compelling, yet extremely complicated.

SfN 2012 – Highs, Lows, & Beignets

Last week, I had the opportunity to attend the 42nd Annual Meeting for the Society for Neuroscience (SfN) in New Orleans.  For a quick frame of reference, imagine over 28,000 lovers of brain science toting 3 x 5 posters  and joining together for one of the largest academic conferences in the world.  From the staggeringly enormous poster hall extending from row A to row FFF to the sheer volume of information being shared in various special lectures, symposia, minisymposia, and (oh yes) nanosymposia, this meeting is surely a handful and, most definitely, a wonderful head-ful.

This was my second time to attend the meeting, making my experience infinitely more enjoyable.  Not to mention, this year’s Neuroscience 2012 App was super helpful for the iProduct obsessed #guilty.  Last year’s experience was so overwhelming I couldn’t even muster up a blog post to recount the meeting.  This time, I’ve at least managed to retain enough information to share about some brief highs, lows, and my newfound love for Beignets.


I was able to check out several posters relevant to our work in lab.  For instance, one group from Medical University of South Carolina presented work on graph theoretical analysis of resting state fMRI data in autism.  Sound familiar?  Interestingly, they found that individuals with autism  displayed less long-range connections forming in brain networks from childhood to adulthood, further supporting the functional underconnectivity hypothesis in autism.  Our whole lab was also intrigued by work from Tracy Bale’s group at Penn showing that early life and adolescent paternal stress can lead to stress pathway dysregulation in offspring in mice.   This finding adds a twist to the already complex picture of maternal stress in autism.

Another high was having the work our lab presented featured on the Simons Foundation Autism Research Initiative website: http://sfari.org/news-and-opinion/conference-news/2012/society-for-neuroscience-2012/anxiety-drug-enhances-brain-connections-in-autism. Talk about making my day.

I also got to attend several lectures at the meeting.  During her talk, Amy Arnsten of Yale discussed how chronic and acute stress can cause both structural and functional changes  in the prefrontal cortex (our decision making/judgment call part of the brain), effectively taking it “offline” during stress exposure.   Barbara Sahakian of Cambridge gave a lecture on the ethics of so-called “smart drugs.”  Most strikingly, she shared about the increasing off-label use of stimulants, such as the anti-narcolepsy drug modafinil, to improve cognitive performance.   She even showed how easy (and illegal) it is to purchase these prescription drugs online.

Lows:  I’m sure that by now most people have heard of and been baffled by the University of Chicago professor’s Facebook blunder.  I don’t need to justify this man’s misstep with a rant about women in science, etc.  Just know that if there was a “low” from SfN 2012 (or for society at large) this one definitely makes the cut.

Beignets:  How can I describe the powdery fried goodness that was my first taste of a beignet from Cafe Du Monde?  Let’s just say that my powdered sugar moustache was worn proudly and that I may have come home with some mix for my husband.

Tuesday Thoughts: Autism, Hurricanes, and Mud

A big theory in autism research involves what is called prenatal stress, or maternal stress.  The idea is that a stressful event, such as a hurricane, experienced during a woman’s pregnancy may lead to an increased risk of her child having autism. Several studies supporting this idea have been published.  For example, one of my advisor’s papers, published in 2005, demonstrated that the experience of stressors during a specific time period during pregnancy (weeks 21 to 32) may be related to an increased risk of autism.  Stressors were assessed via surveys and included events like the death of a spouse or being fired from a job.

Confusingly, however, these results conflict with those of very recent studies.   It seems this idea may not be as simple as originally thought. This past June, a paper was published that did not find an increased risk of autism associated with prenatal stress.  This study examined many of the same stressors experienced by pregnant women as those of the above paper, yet the authors did not find the same results.

Results from another study, presented at the 2012 International Meeting for Autism Research, further complicate this picture.  The study examined the incidence of autism in children of mothers who experienced psychosocial stressors, such as physical abuse, during pregnancy.  The twist is that physical abuse experienced during pregnancy was not associated with an increased risk of autism.  Instead, children of women who experienced fear of their partner or physical or emotional abuse in the years just before giving birth had a higher risk of autism.

Why did two very similar studies produce opposite results? Why does it seem that physical abuse during pregnancy is not associated with autism when abuse beforehand is? Many reasons may lie beneath these conflicting and confusing results.  Potentially, gene variants associated with autism are playing a role alongside prenatal stress in causing this disorder. Or different techniques used to carry out the above studies may have contributed to the differing findings. Otherwise, the reasons are about as clear as mud.  For now, the best we can do is put on our finest analytical goggles, jump into the data, and start sorting through the mud.

Photo source: http://earthobservatory.nasa.gov/IOTD/view.php?id=79008

Tuesday Thoughts: Fight or Flight

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.