Tuesday, May 26, 2009

"Motivation": Cortex vs. Limbic System

I speculate that dopamine affects how easy or hard it is to initiate activities. This particularly seems to affect activities requiring significant energy, like exercise, and/or decision making, like planning a trip or moving. I introduced this idea a little bit in an earlier blog post.

I found that when I was dopamine deficient, I couldn't initiate exercise myself. I could tag along if someone else initiated it though, and feel better during and after. A woman from my church invited me to go walk with her on Tuesday mornings, and I could do that. My husband and I joined a twice weekly yoga class, and I could go to that.

It seemed silly to me that I couldn't initiate these sorts of things myself. In the past I treated this as a moral failing, and beat myself up about it. That made me feel awful, but I still mostly wouldn't be able to do it. This most recent time I was more accepting about it. I still tried to convince myself to go exercise, but was more gentle about it. Sometimes I would succeed in going and exercising by myself, but mostly I wouldn't. Instead of treating it as a moral failing, I treated it as a science experiment. What was different about the times when I was able to go and exercise?

Once I got the dopamine increased enough I could mostly initiate exercise by myself no problem. It wasn't that I was trying harder, or being more morally upright. It just felt like a road block that had been there was just gone.

When I studied more about dopamine, and what affects it, I realized that dopamine levels seemed to correspond to how easy or hard it was to initiate that sort of activity. When dopamine levels were mostly low, I would only be able to do it as a follower or after some sort of experience that sufficiently increased dopamine. Now that dopamine levels are mostly ok (got the bupropion working right), I can initiate exercise myself most of the time, except after experiences that sufficiently decrease dopamine.

All this made me realize that the concept we call "motivation" really has more facets than I'd realized before. What you think about how much you "should" do something, how much you want to do it, and what you think about where it ranks in your priority and value schemes are one set of factors. How you feel when your think about doing something -- how your biochemistry reacts to the idea -- is another. They're controlled by different parts of your brain (cortex vs. limbic system), and are not always in sync.

I suspect that the latter part is the one that's more tied into physiological state -- how much dopamine, energy, etc. you've got to start with and how those change in reaction to your proposed activity, like exercise. It can agree and reward you with an added burst of dopamine, which makes it real easy and appealing to go off and initiate the activity. It can also disagree and make you feel uneasy about it (not sure if this is it decreasing dopamine, increasing stress chemicals, or both), and make it real hard.

It seems to me that in some cases the meaning of "motivation" is pretty clear:
  • Motivated = cortex decides to do it, limbic system agrees, you do it
  • Unmotivated = cortex decides not to do it
However, what do we say about the case where the cortex decides to do it but the limbic system disagrees? Generally this is where things gets tough and we are prone to beat ourselves up. I bet we end up in this state more often when dopamine is low. I also bet that when dopamine is low and we end up in this state, we're much less likely to be able to force ourselves to initiate the activity anyway. Here's the trap: the way we think about failing to initiate activities like this can further decrease dopamine, making it even harder next time.

I certainly find myself in that state much less often now. For a few months, before using the bupropion to increase dopamine tone, I was in that state almost all the time. I exercise much more often now than I did then. I don't actually decide to exercise any more often -- likely I decide to do it less frequently. The difference is that now it's much easier to follow through on that decision. Does that reflect a difference in "motivation" or not?

Friday, May 15, 2009

Evaluating food risk: "spices" vs. "fava bean flour"

My husband Randy and I recently moved to Pittsburgh. He likes a local chain here called Panera's that looks like a bakery and projects a more-than-usually convincing image of wholesomeness. From the ordering line you can see a glimpse of a convincingly realistic bakery kitchen. This resembles the sort of place where you'd expect the baked goodies to have been baked on-site.

The first time we went there, I wasn't yet ready to take a risk on eating anything there. After all, baked goods are at risk of containing hidden potato starch. I watched him eat a very yummy looking souffle thingy and, truth be told, really wanted to eat one too.

The second time we went there I had decided to take the risk, ask about ingredients, and not feel left out this time. I was reassured that there was a sign behind the counter saying you could ask to see the list of ingredients. I asked for the ingredients for the most conservative souffle thingy they had: the Four Cheese Souffle.

I scanned the list of ingredients quickly looking for nightshade. I didn't see any, but I did see "spices," which can include hidden nightshade (usually paprika or other peppers). I asked if they knew which "spices" it contained, and if I could see the container. They looked at me funny, then looked at each other. I suddenly realized that they must not actually be made on-site. In retrospect, I should have figured that out from the length of the ingredients list, but I wasn't thinking that fast.

I went back to the ingredients binder and looked at the next most conservative item, the Egg & Cheese Breakfast Sandwich. If you go to Panera's Breakfast Sandwiches Menu, you will see that at first glance this contains 3 ingredients, and 12 descriptive words to positively influence you're attitude towards them. However, if you click on "Egg & Cheese" you get the real list, containing 36 ingredients, 29 of which are in the "two slices of freshly baked Ciabatta." The most memorable of these are "fava bean flour" and "distilled monoglycerides."

Admittedly this isn't as bad as an Egg McMuffin which at first glance contains 5 ingredients, but 64 when you dereference the ingredients (35 in "English Muffin", 2 in "Egg", 14 in "Canadian Style Bacon", 13 in "Liquid Margerine"). Now, a lot of those are duplicates, but it would still be a lot if the duplicates were removed. Also, that list includes scarier things, including "high fructose corn syrup", "partially hydrogenated soybean oil" and "artificial flavors" which Panera's happily doesn't.

Despite the carefully crafted image Panera projects, it would be unjust to consider just one of these breakfast sandwiches as "processed" -- they both are. Both are engineered to stimulate your senses in ways that mere unaided nature cannot compete with.

That's what I thought of when reflecting back on the experience. What I thought of while standing around hungrily perusing the ingredient binder is this: which is riskier, "spices" or "fava bean flour"? I vaguely remembered that fava beans have some pretty potent physiological effects, though I couldn't remember what they were. Most importantly, I haven't eaten any since I overcame the cholinesterase inhibitor stuff and started carefully adding foods back in. I didn't even dare to think about the distilled monoglycerides...

In the end, I decided to go for the Egg & Cheese Breakfast Sandwich as the least of three evils (the third being to sit there hungry watching Randy eat his souffle). It was reasonably tasty, and happily I did not notice any nasty side effects of having eaten it.

The next day I made an egg & cheese sandwich at home. The eggs, cheese, and butter were local. (I later got to meet the farmer in Ligonier who raised the eggs.) The bread was organic and baked at Whole Foods. It was yummier, and led to less angst.

Saturday, May 9, 2009

Differential reactivity to emotional inputs and BDNF

Someone on the 23andme forum posted the following paper abstract:

1: Am J Med Genet B Neuropsychiatr Genet. 2009 Apr 22. [Epub ahead of print]
BDNF, relative preference, and reward circuitry responses to emotional communication.

Gasic GP, Smoller JW, Perlis RH, Sun M, Lee S, Kim BW, Lee MJ, Holt DJ, Blood AJ, Makris N, Kennedy DK, Hoge RD, Calhoun J, Fava M, Gusella JF, Breiter HC.

Motivation and Emotion Neuroscience Collaboration (MENC), Athinoula A. Martinos Center in Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Brain derived neurotrophic factor (BDNF) regulates neural development and synaptic transmission. We have tested the hypothesis that functional variation in the BDNF gene (Val66Met polymorphism, rs6265) affects brain reward circuitry encoding human judgment and decision-making regarding relative preference. We quantified relative preference among faces with emotional expressions (angry, fearful, sad, neutral, and happy) by a keypress procedure performed offline to measure effort traded for viewing time. Keypress-based relative preferences across the ensemble of faces were mirrored significantly by fMRI signal in the orbitofrontal cortex, amygdala, and hippocampus when passively viewing these faces. For these three brain regions, there was also a statistically significant group difference by BDNF genotype in the fMRI responses to the emotional expressions. In comparison with Val/Met heterozygotes, Val/Val individuals preferentially sought exposure to positive emotions (e.g
., happy faces) and had stronger regional fMRI activation to aversive stimuli (e.g., angry, fearful, and sad faces). BDNF genotype accounted for approximately 30% of the variance in fMRI signal that mirrors keypress responses to these stimuli. This study demonstrates that functional allelic variation in BDNF modulates human brain circuits processing reward/aversion information and relative preference transactions. (c) 2009 Wiley-Liss, Inc.

This is interesting to me. I'll get to why further along in the post, but first I've got some background to fill in:

I've been looking into how the limbic system, which includes the amygdala and hippocampus, is involved in processing and generating emotional communication (facial expression, body language, tone, that sort of thing) and physiological responses to such communication.

It seems to me like for some people, including me, the output of the emotional communication detectors seem to be wired to physiological responses with a much higher gain than they are for other people, like my brother. Put him in a room with an angry person and he'll be aware of it in an abstract sort of way, but physiologically seem unaffected. In the same situation my heart rate will be going crazy and I'll feel a strong urge to run for the exit, even if I know intellectually that the angry person isn't a threat and that I have nothing to do with whatever it is he's mad about. I've put a fair bit of effort into trying to understand this discrepancy.

The limbic system is designed to keep us from getting killed and/or eaten. It responds quickly, but it's not big on context or discernment. It's perfectly capable of causing sympathetic activation, releasing epinephrine (aka adrenaline) and all those other fun stress response chemicals, before the cortex has an opportunity to weigh in on the matter. Anyone who has rounded a corner while hiking and found themselves jumping backwards with their heart racing from what the cortex easily identifies a fraction of a second later as a stick knows this.

Your cortex can then either work to get the limbic system to settle down or make the situation worse depending on how you end up thinking about the event. Even best case though, it takes time for all those nasty stress chemicals to dissipate. So, in the example of me and my brother in the room with an angry person, I don't believe that the difference is due to a difference in how we're thinking about things.

These sorts of differences in reactivity can also be related to a difference in life experience. The limbic system learns and adapts over time based on earlier outcomes -- what circumstances turned out to be dangerous or not. Once you burn your hand on a stove you find yourself acting wary thereafter around stoves even without conscious thought. This is why burning your hand is so much more effective than someone repeatedly telling you to be careful around the stove (limbic vs. cortical processing). However, based on stories my mother told me, the difference between my and my brother's reactions to aversive emotional output in our general vicinity was apparently present from infancy, so I don't think limbic training is enough to explain it.

All this leaves me looking for a genetic basis for this difference. I may have found one potential piece of the explanation in rs1801252, a SNP in the ADRB1 receptor. If I'm interpreting the reference on the SNPedia page right, the fact that I'm homozygous for the atypical version of this (GG) would lead to a more drastic than normal cardiac response to a given level of epinephrine. However, it wouldn't affect the aspects of sympathetic nervous system activation other than those mediated by the beta 1 adrenergic receptors, and I don't get the impression that my brother is experiencing those other effects either. I think he's not ending up with as strong a signal from the emotional state detector system and/or experiencing a lesser limbic reaction to it in the first place.

This brings us back to why this study seems like an interesting potential lead. They're showing a pretty strong difference in limbic response to facial expression based on differences in genotype for BDNF. I've got the version of that SNP that seemed to have the stronger response (CC = Val/Val). I wonder what version of this my brother has? I guess I've gotta get him genotyped to find out...

There's obviously more to it than that. About 68% of the population are also CC on this SNP. If 68% of people have as strong a physiological reaction to emotional output in their vicinity as I do most of them hide it well. Elaine Aron has written a series of books about "highly sensitive people"(HSPs), which I think corresponds fairly well to what I've been talking about. She calls this trait Sensory-Processing Sensitivity (SPS) and estimates 15 to 20% of people to have it. I wonder how well her concept of the SPS trait would correlate with the BDNF genotype and fMRI testing results described in this paper.

I also wonder about how all this relates to autism spectrum disorders. It seems like part of what's going on there is that either the parts of the limbic system detecting the emotional state of others doesn't work well, or the degree to which that information impacts and/or is accessible to the affected individual is muted enough so as to cause them problems. This seems potentially a more extreme degree of the same effect that I've been talking about. Perhaps it's all one spectrum: people like me and other HSPs at one end, people like my brother who match social expectations on this issue in the middle, and people with various degrees of autism spectrum issues at the other end. I could be totally off base here -- I haven't looked into the literature on this issue much at all -- but I think it's an interesting area for study.