Wednesday, July 17, 2013

Weekly Brain Update: decisions, decisions...


In the past two weeks the Brain Update was focused on the prefrontal cortex, which has been characterized as a brain area that integrates information and is sensitive to the emotional intensity of events.  This week we turn our attention to an area of the brain that receives information from the prefrontal cortex and is pivotal in translating that information into action: the dorsomedial striatum.

The striatum’s function is to influence motor behavior.  When you decide (prefrontal cortex) that it’s time for your midmorning coffee jolt, you must convert that decision into moving out of your chair, reaching for your wallet, making your way to the Coffee Procurement Facility, and extracting the stack of money from your wallet in exchange for the magical elixir. Meanwhile, you smell the aroma of the coffee, and the baked goods that go so well with it.  You hear the familiar voices of the baristas and your fellow addicts, and you experience the initial rush of that first sip.  All of these sensory experiences are processed by various areas in the cortex, and then are sent to the striatum.  If the decision to get coffee is followed by the positive outcome of the coffee’s effect, then the context surrounding this process gets linked to the enjoyable experience, and tomorrow your decision will lead you to the same place to get more coffee.  With enough experience, the role of the prefrontal cortex in the decision-making process is minimized, and the striatum takes over.  Habit formed.

You can understand why neuroscientists are interested in how the striatum converts an idea into action. It would be possible to help someone who has a serious addiction, to something like cocaine or heroin or nicotine, if the neural basis of compulsive behavior was understood.  The authors of this week’s featured article also point out that even a minor malfunction in this system can lead to disorganized behavior, like that observed in obsessive-compulsive disorder or schizophrenia. 
This image is from a very cool study in which the researchers traced the path of new neurons in the hippocampus.
In this week’s Journal of Neuroscience, Ferguson, Phillips, Roth, Wess, and Neumaier have published their research entitled Direct-Pathway Striatal Neurons Regulate the Retention of Decision-Making Strategies.  Remember the awesome viral-vector optogenetics technique from last time?  These authors used a very similar approach, but instead of selectively activating a set of neurons with a light, they used a drug that would only affect the neurons with a particular receptor protein inserted into them.  So, the dorsomedial striatum was injected with the viral vector, which was taken up only by cells that make a specific neurotransmitter and are known to be connected to an output of the striatum, the so-called “direct” pathway.  They injected two types of receptors, one that would stimulate the cells and one that would inhibit them.  Once the receptors were expressed on this small population of cells, the drug that activates the receptor, but would have no other effect in the rat, could be injected.  With Ferguson and colleagues’ technique, they could target a specific population of cells and thus show which part of the striatum’s complex circuitry was responsible for changing behavior. 

The researchers examined the effect of this technique on decision making in rats.  They trained the rats to press two levers for food.  Pressing one lever gave the rat a single food pellet.  Not bad, if you’re a hungry rat.  Pressing the other lever, however, led to delivery of four food pellets: even better if you’re a hungry rat.  Thus, one lever was deemed “high-reward” and the other “low-reward” and the rats demonstrated a clear preference for the high-reward option. 

Whether the neurons were stimulated or inhibited during the training, the rats were still able to make the right choice.  But, if they were asked a week later to do the same task, the ones that had their cells inhibited had trouble learning the difference between high and low reward levers, and they didn’t show a strong preference for the high-reward.  Conversely, the rats that had their cells stimulated a week earlier learned the difference more efficiently and showed a greater preference for the high-reward option.  One of the most interesting challenges in understanding addiction is to describe the brain changes that occur when a person develops a habit and permanently alters their need for a drug.  Even after years of abstinence, an addict will report that they crave the drug, especially if they find themselves in a drug-related situation, like the coffee shop or a bar.  Ferguson and her colleagues suggest that the neurons they studied in the dorsomedial striatum are involved in this long-term change in the brain’s response.
Lace-weight cashmere (above) or classic shetland wool?

So which of the following would you choose?

If you have prior experience with cashmere and you enjoy making lace, you might opt for the pretty green yarn, it being your “high-reward” option.  But what if you are currently on a Fair Isle knitting kick?   It depends on your experience.  

I expected to be cured of the fair isle compulsion for awhile once this was done.
Were you especially pleased with your latest Fair Isle project?  Are you in the same context (season, maybe) as when you had such an enjoyable experience making steeks? Any positive past knitting experience might have changed the sensitivity of your dorsomedial striatum, which would influence the choice you make in beginning your next project.
I find the combination of colors so much fun to arrange.

But, this lacy confection is appealing, too.

Monday, July 8, 2013

Weekly Brain Update: Regulating Emotion


Thank you for your comments on last week’s Weekly Brain Update.

The July 3 issue of the Journal of Neuroscience was full of interesting articles and has provided yet another example of how the prefrontal cortex relates to knitting.  I wonder if this will be the case every week?  I did try my best to devise a link with other articles, ones that focused on hyperalgesic priming, enhanced visual cortex activity in people with amygdala damage, epigenetic regulation of novelty-seeking, and monkey eye-hand coordination, but the prefrontal cortex paper won.

In the article entitled Ventromedial Prefrontal Cortex Encodes Emotional Value, the authors frame their work in terms of neuroeconomics*: decision making with regard to money is dependent on brain-mediated emotional experiences, both negative and positive.  One example that they give is how a nice garden might induce potential home-buyers to spend more on a house than they would otherwise.  There is also evidence that positive emotion increases the likelihood of impulsive spending, a common experience to anyone who never leaves their favorite yarn store empty-handed. 

Regulating positive emotion is also important if you’re trying to limit your food intake.  The sight of a cake, or a bag of chips, or a stack of chocolate chip cookies automatically stimulates the reward areas of the brain, including the ventromedial prefrontal cortex (vmPFC), which computes the value of those items and makes a comparison with one’s eventual goals, such as fitting into last year’s Fall wardrobe.  When making a decision about whether to convert the action of looking to that of eating, research suggests that how enticing the object is perceived and how easy it is to resist relates to one’s ability to regulate emotion.  If you are able to redefine the cake as a mixture of oil, sugar, and flour and to talk yourself out of eating it, you have probably done so because you’ve lowered the value of the cake by decreasing the activity in your vmPFC.
 
Brownie has a space reserved on top of the Pretend Yarn Store
Do you find the mere sight of yarn to be a positive emotional experience?  After years of trying to impose some order on the stash, I finally decided to display it.  Now I can look up from reading/grading/writing emails and get a little dose of reward.  Anyone visiting me looks at the display and wonders about my sanity, not understanding how years of playing with yarn has given it the special power of making me happy to see it.

The research by Winecoff, Clithero, McKell Carter, Bergman, Wang and Huettel is focused on the role of the vmPFC in the perceived subjective value of rewards.  Their study involved asking people to rate the emotional content of a range of images, some being very positive, like a cute puppy, and some being very negative, such as an infected cut [the actual pictures are kept secret so that participants in the studies have not seen them before; these examples are guesses]. They were instructed to either experience the emotional content of the image (the “experience” group) or to attempt to regulate the emotional impact of the image using a cognitive reappraisal strategy, by detaching themselves from it, or viewing it objectively as having no relationship to oneself (the “regulation” group).  After giving the participants ample practice experiencing and regulating emotion, the researchers then rolled the participants into a function MRI machine in order to examine how much the vmPFC was activated.  They expected that there would be a decrease in activity when a person was regulating their reaction to an image that has been deemed by many to induce positive emotion.  They also proposed that there would be an increase in vmPFC activity in the regulation group when they viewed sad images, which has been demonstrated in other studies.  They showed the expected results, providing some clarity regarding the role of the vmPFC.  It’s not merely a brain area that is responsible for regulating emotion, but also is capable of tracking the degree to which an event or image is positive or negative.      
 
https://plus.google.com/+websyarn/posts
Does this image increase the activity of your vmPFC?
We have all had the experience of buying yarn that we didn’t need, but it’s difficult to resist (high activity in vmPFC) when the yarn is arranged in a rainbow of colors, neatly stacked in sweater-sized piles in the yarn shop.  I think that this is especially problematic for me when I go to WEBS—I have such a positive emotional attachment to that place that my vmPFC must be very active when I walk through the door, and then it goes into overdrive as I approach the warehouse in back [see this visitor’s picture], with the stacks of yarn, neatly arranged in bags.   If I were in the “experience” group in Winecoff et al.’s study, I would be instructed to revel in the joy that is the WEBS warehouse.  If I was in the “regulation” group, I would be instructed to consider the yarn as anyone else might see it, as something that does not relate to my interests, or as mere piles of cotton, silk, wool, and alpaca that are not important and have no specific purpose.  I’m not sure the attempt to regulate my emotion would be strong enough to overcome the impact of WEBS on my wallet, but there might be some barely-detectable decrease in the activity in my vmPFC.

One idea that this research makes me consider is how can we strengthen the function of the vmPFC so that it is easier to regulate emotion?  Stress can interfere with PFC function in general, so it makes sense that it is more difficult to make good choices when stress levels are high.  I won’t be surprised to learn that regular exercise promotes the function of the vmPFC.  I’ll look into it!

*neuroeconomics is a very interesting subfield of neuroscience.  See the following links for more info: Society for Neuroeconomics conference,  NYU Center for Neuroeconomics, Stanford Neuroeconomics.

Saturday, July 6, 2013

Engineering update

I hope your July is going as well as mine!
Oogy-spun teal (emerald?) alpaca yarn is so nice.

I dyed this wool yarn several years ago.  It came from a farm nearby.

I peeked ahead in July and am looking forward to some of the lace patterns I saw mid-month...

Thursday, July 4, 2013

July Engineering

Dear Oogy,
I have found a few more UFOs that eluded detection last month, so I'll be joining you in extending those projects into July.

Here is my plan for our reverse engineering project for July: I plan to take some of the design features in this sweater
This is "Spice Variety Sweater" from last fall's Territory Ahead catalog.  A search of their website suggests that it is not currently available, probably because it is approx. 90 degrees outside.
 and use this yarn to make my own version.
The teal yarn is Oogy-spun alpaca!

The perpetual knitting pattern calendar will determine the portion that gets done each day.
I don't plan to make the sweater as long as the original, but I like how the individual patterns are put together.  You see that I didn't really get very far today, so we'll see how it goes.  We cannot be surprised on July 31st if we have another UFO on our hands.

It was very warm and humid today, which made working with the wool/silk/angora blend yarn a bit unappealing.  Brownie had this to say about it:
I hope you are staying cool, too!
Love,
Neuro

Tuesday, July 2, 2013

Weekly Brain Update: Working Memory



In an effort to bring more neuroscience to the Knit with your Brain blog, I begin this week with a new feature: Weekly Brain Update.  Each week the Society for Neuroscience publishes an issue of the Journal of Neuroscience.  This is a premiere journal with a broad range of neuroscience articles, including ones that are focused on cellular and molecular mechanisms, as well as ones that describe the neurocircuitry of complex human behaviors.  My plan is to choose an article from each issue and describe to you how the research relates to knitting.  My real goal is to motivate myself to read the journal every week; a secondary benefit will be to increase the neuroscience content of this blog.

A 16-stitch repeat that requires a hard working memory

One article from the June 26 issue has especially caught my attention.  It is about working memory and the brain mechanisms that allow us to hold information in our minds long enough to make links between events.  As a knitter, you might think about the process by which you learned the knit stitch, the sequence of events that had to happen in a particular order to form one stitch after another.  By the time you get to the step of transferring the completed stitch from the left to right needle, you needed to remember what was the first step from several seconds before.  After some practice, the sequence gets unified, and you don’t even think of the knit stitch as a series of steps anymore.  Working memory is the process of keeping the relevant information at the conscious level for a short time (it is also called short-term memory by some) so that long-lasting memories can be established by linking events together. 

The brain area that many believe makes working memory possible is the medial portion of the prefrontal cortex.  It resides in the front of the brain:  if you hold your pointer fingers alongside your nose, right up against your face pointing straight up, you’ll be pointing to the medial prefrontal cortex.  Someone who has trouble staying focused on a project might be experiencing some disruption in this brain area, which has been proposed as a mechanism for attention deficit/hyperactivity disorder.  Stress can disrupt this area, leading to a range of consequences that occur when the stress is severe or chronic.  

So you can see why it is interesting to find an article about the mechanism by which the prefrontal cortex contributes to working memory.  What turns out to be even more interesting about this article is that the researchers have used the most amazing new neuroscience tool: optogenetics!  Before this technique was developed the only way to manipulate a circuit in the brain was to inhibit or excite neurons near the circuit, or to alter the function of a single neuron, which provided very limited information about the whole circuit.  These old methods were also very slow compared to the processing speed of our amazing neurons.  With optogenetics it is possible to alter a very specific population of neurons for a very short time without affecting their normal function.  The neurons are altered by injecting a virus with a DNA sequence for a light-sensitive protein into a brain area.  Only a specific population of neurons will take up the DNA, depending on how it is tagged with a molecule that only that population of neurons uses (this is where my understanding of optogenetics is weakest).  Later, when the researchers want to alter the function of those neurons, they shine a laser nearby, which causes a reaction in the light-sensitive protein and either excites or shuts down those neurons.  If you want to know more about this technique, I highly recommend the TED talk by Ed Boyden: A Light Switch for Neurons.  I don’t think Dr. Boyden is at all confused about optogenetics!

Now, back to this week’s article.  Researchers at the University of Wisconsin-Milwaukee examined the role of the medial prefrontal cortex in forming a memory of an unpleasant event in rats.  Rats show overt signs of fear that we can see easily, in the form of freezing.  The rat remains very still for a period of seconds, sometimes minutes, allowing it to avoid detection in dangerous situations.  The researchers can easily control how dangerous a situation is to the rat, by pairing a sound with a brief foot shock. The shock doesn’t hurt the rat, but it is noticeable and not pleasant, so the rat pays close attention to the context and anything unique in the context (like the sound) in which this annoying event has occurred.  The greater the number of pairings between a noticeable sound and a foot shock, the more dangerous the sound will seem to the rat.   In that context or when hearing that sound, to the extent that the rat remembers, it will freeze for a period of time, depending on the magnitude of the perceived danger.

For the rat to benefit from this ability to sense when dangerous events are likely, it would need to link specific aspects of the situation that occurred close in time to the unpleasant event.  This can be examined by researchers who let some time elapse between the presentation of the sound and the foot shock.  This is a challenge for the brain!  Link an event that happened before to one that is happening later, when the neural trace of the early event would be gone.  Enter the medial prefrontal cortex, which is thought to somehow keep the information going when its source is no longer providing it.  Gilmartin, Miyawaki, Helmstetter, and Diba (2013, J. Neurosci, 33(26): 10910-10914) have provided evidence that the medial prefrontal cortex actually does this job.  They injected the medial prefrontal cortex of rats (which were anesthetized and positioned in a special frame that allowed the researchers to target the brain area accurately) with a virus that would deliver ArchT to the neurons there.  Then they implanted a tiny laser fiber just above where this light-sensitive protein was delivered.  They waited about 2 weeks for the rats to recover from surgery and when the light fibers were turned on, the neurons nearby shut down.  Their experiment was to turn off the neurons during the time that elapsed between the sound and foot shock, essentially removing the ability of the medial prefrontal cortex to keeo the trace in working memory.  They had a bunch of control groups in which the light was on at different times.  Then on the next day the rats were tested for the strength of their memory.  The rats that had the full function of their prefrontal cortex remembered both the context and the sound as scary.  However, if the prefrontal cortex was taken offline during the interval between the sound and the shock, the rats did not remember that the sound was scary.  This effect was very specific to the link between the sound and foot shock; the rats still showed fear in the context by itself.  The optogenetic technique allowed the researchers to turn off the brain area for a very short time,  a mere 20 seconds, which provided the evidence that was lacking to give the prefrontal cortex full credit for its working memory function. 
This would not be fun to do if we had to constantly consult the pattern.  Luckily our working memory keeps track of where we are in the pattern as each repeat is completed.
What would happen to our ability to learn the knit stitch if the medial prefrontal cortex was offline between “insert right needle into front loop of stitch on left needle” and “transfer newly formed stitch to right needle”?  We’d have to keep looking up the intermediate steps of “wrap yarn around the back of the right needle” and “draw loop on right needle through the loop on left needle” and the sequence would not get unified into a single event, the knit stitch.  We could tax the medial prefrontal cortex even more by trying to learn a lace or fair isle pattern repeat.  Next time you accomplish those amazing feats, consider thanking your medial prefrontal cortex!

Monday, July 1, 2013

FOs

Dear Oogy,
I've done all I can for our June project.
The fair isle vest is done.

I did try it on and it fits great.
I feel obligated to include a disclaimer: this is not strictly an authentic fair isle project.  First, it was not made with shetland wool, but instead with Knit Picks Palette, which is absolutely lovely with a color range that is hard to match.  I have a large portion of that color range in my stash, and one of the best aspects of this project was deciding which one to use next.  Second, I made no effort to align the patterns.  They are quite random in their horizontal placement.  I did, however, preserve a few features of a traditional fair isle project.  I used steeks, and I limited each row to 2 colors.  There are also 2 design features that I followed throughout the project.  One is that as I approached the top I chose patterns that were progressively shorter.  The other is that between each pattern is the same 2x2 design, with the same foreground color each time.  Now that this vest is done, I am quite eager to do another fair isle project.
The other FO is Clapo-Ktus.  This picture is just before it went in the sink.  It is now laid out on a table downstairs, beaconing Brownie to lay on top of it.

I liked making this shawl and I will use the pattern again.  One challenge that was especially an issue at the end was the effort required to drop the purl stitches to reveal the ladder rungs.  This is merino wool lace weight and has a bit of grab to it.  Brownie, as always, was a big help.
I'm excited to begin the July project!
Love,
Neuro