If high sensitivity is so costly, why is it still around?

Evolution is often sold as a species/population converging on a single ideal solution for a population.  This is incorrect.  For one, the ideal solution in 2013 is not necessarily the ideal for 2014.  Peter and Rosemary Grant demonstrated that ground finch weight and beak size varied from year to year, that this corresponded to shifts in food availability due to weather, and that the change was driven by genetics, not starvation.  Beyond that, there is often more than one good strategy at a time.  Wal-Mart and Rodeo Drive both technically sell clothes, but they’re not in competition.  When you combine temporal variation with the existence of multiple viable strategies, you get population diversity.

What this means is that even if a gene is very, very bad, it’s probably there for a reason.  At worst, it was a local optimum for a problem that no longer exists.  See: sickle cell anemia.  Sickle cell is a very nasty disease caused by a single gene.  But being heterozygnous for the sickle-cell allele gives you some resistance to malaria.  Which is useless if you live in the USA in the 2000s, but highly relevant if you’re in Africa now, and even more so Africa in the past.  That is why the allele stuck around.

Moreover, the returns to a particular strategy depend on other people’s strategies.  You’ll make more money selling cheap, mass-market clothes if there’s no Wal-Mart in your city.  This is known as frequency dependent selection.

The moral of this story is: any time you see a genetic trait that looks negative but is widespread, look around.  It’s almost certainly either linked to an advantage you aren’t seeing, or is advantageous under a different set of circumstances.

As we talked about previously, this appears to be the case for the trait known as sensory processing sensitivity .   Belsky et al have an exhaustive synthesis of various ways high sensitivity has been shown to correlative with both unusually positive and unusually negative outcomes, depending on environment.  You remember the DRD4 7R mutation, that was associated with ADHD and susceptibility to the individual’s mother’s trauma?  More prevalent in nomadic and nomadic-descended populations than sedentary.  And carriers do better than non-carriers when nomadic but worse when sedentary.

I tripped a little bit reading this, because something associated with ADHD and nomadicism seems like a novelty seeking gene, which is associated with extroversion.  High sensitivity is highly correlated with introversion, and even the extroverts among them have very different brain patterns than low sensitivity extroverts.  I got this from Quiet, which the library has unfortunately taken back so I can’t look up the specifics.  I wonder if the extraverts were the ones who had good childhood environment.  And it turns out this isn’t the only allele linked with both high sensitivity and ADHD.  5-HTTLPR short is too.

Quantifying the advantages of high sensitivity in humans is hard.  Luckily, there’s a number of very good animal models.  That’s a severe understatement.  A more accurate statement would be “you can’t throw a rock without hitting a member of a species that demonstrates a shy-bold continuum.”  This may mean we haven’t defined our terms well enough, but it could also mean that almost all species demonstrate frequency dependent selection in sensory sensitivity.  The theme seems to be that higher sensitivity animals are more cautious, and thus get eaten less, but every once in a while a low sensitivity animal blunders its way into something amazing, like a new source of food, or founding a start up.

What we talk about when we talk about heritability

There’s some behavioral evolution stuff I want to talk about soon.  This is great, because it’s what I studied in college and I will be able to contribute something beyond wikipedia synthesis.  In order to really dig into this, I have to explain how we measure heritability.

Heritability“, or h^2, is a very specific measurement in biology.  It measures how much  variation of a particular trait in a particular population is due to genetic variation, relative to the total variation.  It is not a synonym for “genetically determined.”  For example, having two arms is barely heritable, because there’s almost no variation in the number of arms people have.  Of people that have less than two arms, most of them lost them to environmental accidents, not genetics.  There’s no gene for “one arm”, although developmental accidents may have some genetic basis.  Biological sex isn’t very heritable either.  A person’s parents’ sex has very little predictive power on the person’s own sex.    Despite this, number of arms and biological sex is very, very genetically determined

Additionally, a heritability measurement is only valid for the population it was measured in.  In a population in which every individual has exact the same environment will demonstrate much higher heritability for every trait than a population with a varied environment.

Now here is the really weird thing: how sensitive a trait expression is to environmental variation can be influenced by genetics.  High Sensitivity was originally discovered in people who were having severely maladaptive responses to normal stimuli, and was assumed to have a uniform negative effect on people who carried it.  Newer research indicates that the effect is more complicated:  Highly Sensitive People with really good environments do better that Low Sensitive People in those environments.  HSPs in bad environments do worse that LSPs.  Whatever genes cause the trait we call High Sensitivity make a person more sensitive to their environment.  Ellis et al call this biological sensitivity to context.

Lee et al  investigated a particular HSP- associated allele, DRD2 Taq1A, and found that mothers with the gene were harsher parents during a recession than mothers without the gene.  Moreover, they found worsening economic conditions led to worse parenting in everyone, but the effect was more pronounced for mothers with the T allele as opposed to the CC allele.  So a child’s outcome is being affected by their own genetically-driven response to their parents, their parents’ genetically-driven response to the environment, and the actual environment.

I thought what depressed me here was that highly sensitive parents are more likely to have highly sensitive children, which will magnify the negative effects of the recession on children.  Then I read a study showing that maternal psychological trauma was associated with higher disorganization in infants, but only if they had a high-SPS associated allele.*

High Sensitivity is going to come up a lot, so remember that.  But also remember that when journalists talk about heritability, they do not mean what they think they mean.

*The same mutation, DRD4 7-repeat polymorphism, is associated with ADHD.

Sensory input and economies.

Expanding on my metaphor from yesterday, let’s posit three different types of sensory inputs/equations: Trivial (sensory input that is not necessarily effortless to process, but not taxing), Unsolvable (puts you into overload), and Solvable (requires noticeable amounts of processing power).  Unsolvable equations represent either completely  new data, or complex combinations of problems that would be Trivial on their own, but combine in difficult ways.

More concretely:  let’s say you have two sensations, A and B.  Either one on its own is a Taxing problem, but together they’re Unsolvable.  If you manage to move A into the Trivial category (by repeated exposure and processing), that moves A+B into Solvable.  And when you have solved it, you have A, B, and A+B in the trivial category, which will come in handy when you see A+B+C later.  In this way, very small differences in initial processing capabilities can compound into vastly different levels of ability.  Going into overload isn’t just painful, it cuts you off from learning the things that could prevent it next time.

This suggests a huge payoff to investing problems that are right on the border between Trivial and Solvable.  Not only do you move that one thing off your plate, and move some other problems from Unsolvable into Solvable, you create an environment where you can eventually solve the other components of that previously Unsolvable problem.  

[The following paragraphs are free-association at best]

For some reason I’m reminded of Jane Jacob’s The Economy of Cities, in which she postulates that most economic growth follows the following pattern:

  1. I’m doing a thing.
  2. Hurray, I invented a slightly more efficient way to do that thing.
  3. Wait, I could use that new invention to do this other thing.  There’s no demand for it yet because no one knows they want it, but there will be.
  4. Welp, I invited a whole new sector of the economy.

Tim Harford implicitly talked about this in Adapt.  The best economics have several interlocking industries with moderate overlap.  Similar enough that innovations in one can help enough, but dissimilar enough to cause them to approach problems in different ways.  Adapt as a whole is about trying a lot of things quickly, with the expectation that most of them will fail.  One important component of that is minimizing the cost of failure, and one important component of that is recognizing failure quickly.  Which sounds like a sensory problem.

Like I said, this is free association.    I know I’m on to something, but I’m not sure what yet.

I figured it out.

One thing that has frustrated me as I researched SPS has been that I couldn’t connect the macro with the micro.  I know damn well what the macro pattern is (too much noise -> everything is terrible, and also I bump into walls a lot), and I’ve been learning about the micro pattern (auditory, visual, or touch stimulus leads to over-activation of certain areas of the brain), but how did overactivation lead to irritability?    The Threads of Autism (which I’ve since finished) went on and on about teaching people to “organize” sensory input, but it only described the effects of this in macro language (people become more relaxed, more resilient, able to thrive under higher levels of stimulus), but not what that actually looked like in the brain.  Much less why pronating and supinating my wrists in time with my breathing or tapping along my facial nerves was going to accomplish this.

I think I’ve figured it out.  Before I tell you, I want to make it very clear that this is my own personal metaphor, and not something that’s been tested scientifically.  I’m not even sure what it would mean to test it.  But it makes sense to me.

Your/your body’s ultimate goal is to figure out what it should be doing at any given second, and especially if it should be running away from or trying to breed with something.  In order to do that, it tries to work backwards from the sensory input to derive a model of what is actually happening*.  It can then decide how it wants to respond to that thing that is happening.  For example, if you’re wandering through the jungle and hear a twig snap, you would like to know if it’s a delicious herbivore, a hungry tiger, or a human being, and if so, is it from  your tribe or the one you’re at war with.  Past sensory experience is really helpful in this interpretation.  For example, if you’ve heard lots of tigers walking in the jungle, you can pattern match the current sounds against the ones you remember and see how close they are.

But what if it were more basic than that?  We think we just know when and where and how someone is touching us, or how we’re oriented in space, but that is actually something you have to learn.  We don’t notice because it’s mostly done when when we’re very very young, and because it’s done in parts of our brain that we’re not  consciously aware of.  But human brains are actually very plastic, and we devote an extraordinary amount of time and energy to learning how to translate “nerve 43b is firing” to “something happened on my left ring finger.”

My metaphor is as follows:  people with SPS either don’t have the same bank of experiences to pattern match against, or are worse at matching.  So given the same amount of sensory input, it takes them a lot more energy to correctly model the source.  It’s sort of like simplifying a mathematical equation.  If you have something awful with lots of terms you can solve it by hand, but it’s error prone and time consuming.  If you take that same equation and simplify it by removing terms that cancel and grouping like terms together, that same equation can be trivial.

I think the point of the sensory integration exercises is to build up either the database of experiences and/or your skill at simplifying equations.  You can’t give a person every single experience, but you can teach them “this is what stimulus from the trigeminal nerve feels like deep inside your brain.”  This makes it marginally easier to identify, or at least not freak out about, novel stimulus.  It’s like teaching someone about a 3-4-5 triangle.  They’ll not only recognize other 3-4-5 triangles faster, but eventually 6-8-10 and 4.5-6-7.5 as well.

When I started in computational biology, I was all about complex computer simulations.  By my senior year of college, I’d learned to appreciate mathematical models.  They left out details, but that was what let you see the general patterns.  If I’m right, I’m about to undergo the same process for basic sensory data.  And I know I can do it.

*Exception: reflexes

Possibly fictitious diseases of the endolymphatic sac

Last week I asked: what could go wrong with the vestibular system.  I was hoping to have a more satisfying answer by now, but I haven’t.  So here are some random wanderings.

The scientifically suspect book my scientifically suspect first sensory integration therapist gave me suggests “underinflation of the endolymphatic sac”, without anything so droll as a definition of the endolymphatic sac.  No problem, I have the internet.  Wikipedia’s entry on the subject is… weak.  I originally misread it as saying the endolymphatic sac was connected to only the saccule (one of the two linear-motion detecting mini-organs).   The Pictorial Guide To Cochlear Fluids sets me straight on this: all of the various vestibular systems are interconnected, and they all connect to the endolymphatic sac.

An underinflated endolymphatic sac would imply an insufficient amount of endolymph- either because you’re not producing enough, you’re somehow leaking it, or you need extra for some reason  (extraordinarly large semicircular canals?  I don’t know).  The various vestibular structures can’t have their fluid levels too tightly coupled, because that would ruin their specificity, but they are connected via endolymph ducts.  It would (famous last words) make sense if they all had some ideal fluid level, and overflow went into the endolymphatic sac.*

Dr. Internet has pointed me to many descriptions of how an excess of endolymph is bad for you.  And it’s not hard to imagine how a deficit could hurt you.  But is it possible to have enough for the vestibular system, and yet the endolymphatic sac is undesirably empty?  Unscientific Book suggests that because the sac is directly touch with brain fluid, information is reported to the brain through it, and that an underinflated sac can’t do this.  I can’t prove that’s not true, but it strikes me as unlikely to be a large effect.  If I had more faith in the book I’d poke around more, but for now I’m going to leave it.

*Last week I implied the ortoliths (linear motion detecting systems) contained only gel, not endolymph.  In my defense, I thought it was true.  I was wrong.


The magic of placebos

People say placebo effect like they mean “it didn’t work” or “they made it up”; It puts me in mind of Bill’s comment in True Blood: “No offense Sookie, but humans are shockingly susceptible to just about every form of thought manipulation.”The thing is, the placebo effect isn’t in our heads. It’s chemically measurable- through an increase in dopamine levels when told you were going to get an an analgesic, through an increase in basophil levels when injected with homeopathic (i.e. nonexistent) levels of histamine*, and through a changes in ghrelin levels when given different expectations about the calorie content of a shake. The original placebo effect- a decrease in pain when told a sugar pill was a pain medication-doesn’t work if you introduce an opiate blocker. My psych 101 professor said women could gain about half a cup size over six months through hypnosis. And I have seen multiple doctors that spotted things others didn’t, which led to greatly improved quality of life, that also believe in homeopathy.Which leads me to conclude that human brain is just an astonishingly powerful device that hasn’t yet figured out how to properly harness itself. Yet.*Extra interesting because most allergy tests use a saline injection as a negative control. Last time I had it done they told me which one was the control. I wonder what happens if they don’t.

Optimal hammering time

Last month I watched Home, a documentary about a charity offering homes to poor people (maybe just poor single mothers?) at a significant discount.  It focuses specifically on one woman who applied for help and the case worker assigned to her.   Watching it, I was struck by how much the case worker defined her goal as getting this woman this house, rather than helping her, or giving the house to the person to whom it would do the most good.   I thought it was a case of cargo cult, another friend described it as a cultural fixation on helping the poor by making them middle class rather than making being poor bearable.  Either way, it seemed to me like an example of misapplied charity.

Last week I started training to volunteer for a crisis hotline.  One of the things they drill into us is that most callers have a lot of problems we can’t solve.  We have very few tools:  occasionally we make referrals if they have certain  specific issues (e.g.  we’ll offer LGBTQ kids the number for the Trevor Project, or suggest they call 211 to get referrals to programs that could help their material problems), but mostly we listen.  That is what we do.  We are to apply that one tool as best we can.  If it helps, great.  If not, we end the conversation anyway.  There’s a weird tension between “Anything is a crisis if it feels like one to you.  We’re here to listen to anyone, any time, for any reason.”  and “Some people are just black holes, cut them off after 45 minutes.  But they can call back tomorrow.”

The only way I can justify this is by thinking “We have one tool.  It’s impossible to know if this tool is what this person needs.  Even when it is, there are diminishing returns to using the tool.  After 45 minutes, the marginal returns to further use are 0.  Therefore, treating everyone as receptive at minute 0 and no one as receptive at minute 45 is the optimal use of our time.”

I still think the case worker in the movie was pushing her tool too hard, and not listening when the person she was nominally trying to help brought up very reasonable concerns.  But I’m a lot more sympathetic to the myopia now.

The vestibular system

The library took away The Second Brain and there’s a long wait to get it back, so we’ll be putting digestive issues aside for a moment  and talking more about sensory stuff.  While I have a variety of issues that are in retrospect sensory, the driving complaint that drove me to seek treatment was misophonia.  You know how nails on a chalkboard or a crying baby creates a kind of aural pain you can’t block out?  Misophonia is having that reaction to sounds normally considered safe.   http://misophonia-meerkat.tumblr.com/ is full of people are driven to thoughts of self harm or even suicide by very common sounds, like breathing, low bass, and typing.   Luckily, I’m not nearly that bad.  But I also find it almost impossible to concentrate when people are talking, and work in an open office.

I have a new SI therapist (who I have yet to compare to a Guantanamo Bay interrogator, which makes her much better than the last one) who says my problem lies in my vestibular system, so let’s do some recon on that.  The vestibular system has two parts: a series of canals that track rotational acceleration, and two sacs that track acceleration in a single direction.  I wrote several paragraphs explaining exactly how these work, but ultimately I don’t think I added much over wikipedia, so I’m just going to summarize.  The canals and sacs are constructed differently but operate on the same physical principle:  if you have a rigid container holding a liquid, the atoms in the solid share momentum/inertia with each other but not the atoms in the liquid.  That’s why you can spill water by moving a glass very quickly, even if it’s perfectly level the whole time.  The canals and sacs detect this somewhat differently- the canals are filled with an electrically charged fluid (endolymph) that interacts with electrically sensitive hairs when you spin, which triggers a signal to the relevant nerve.  You have three canals, each of which detects rotation in a different plane.  Do not bother reading the descriptions of which plane each covers, they do not make any sense.  Instead, read this article on the axes of rotation for airplanes.  The theory is equivalent and the pilots have much better diagrams.

The sacs have a number of stones or crystals sitting in a gel, and nervous system is triggered when the stone hits the sac wall, bending the hairs on it.   Both sacs provide information on both horizontal and verticle movement, but the uticle is more sensitive to vertical movement and the saccule more sensitive to horizontal.

Note that both of these track changes in movement, not movement itself.  In order to track speed, your brain needs to keep track of your existing state and then calculate the change indicated by the vestibular organs.  It then automagically triggers the necessary changes in posture and eye movement to keep you upright and looking at your target.  That is why you can read when shaking your head, but not when someone moves your book.

Motion sickness is caused by a disagreement between your vestibular system and your eyes about how fast you are moving, which means my trick of looking at a fixed point in the vehicle was exactly wrong.  What I need to do is look outside so my eyes track motion.

At this point, I have two questions:  what can go wrong in these systems, and how to do they relate to misophonia, which is a hearing thing, not a balance thing?

Quick tip: honey for allergies

I alluded to my terrible, horrible, no good very bad allergies in my post on parietal cell signaling, and it struck me that I haven’t worried about my allergies in a very long time . They were the first medical problem of mine that I cured, and I cured them so thoroughly I’d forgotten they were ever an issue.  There probably won’t be any long posts explaining allergic mechanisms because I don’t have a use case for the data, but I thought I could at least tell you what cured me.

To set the stage: it was my senior year in college.  I was on three different medications for my allergies (a rhinocort inhaler, hydroxyzine, and a rotating anti-histamine like Zyrtec or Claritan).  Those kept me from sleeping 14 hours a day or developing debilitating hives, and it even controlled the sinus headaches as long as I didn’t do anything stupid like get on an elevator.  It took about two days for the motion sickness from elevator riding to dissipate.  That’s nothing compared to pre-treatment, when I would arrange my books so I had to move my head as little as possible because that small movement would give me a headache.

A friend suggested local, unprocessed honey.  I had nothing to lose, so I tried it.  I almost immediately dropped down to one medication, and felt better than I had on three.  When I moved to Seattle at the end of the year, my allergies were entirely controllable by honey, and then just gone.  Every once in a while they resurface, I eat some honey, and the problem goes away.

After it worked I started researching.  I remember finding a fair amount of scientific support at the time, but when I went looking for this post I failed to find any peer-reviewed support for the notion.  Additionally,  I realized that I’d been buying honey made from specific pollen based on what tasted best.  But  I was tested for allergies as a chlid, and I barely had pollen sensitivity: the majority of my symptoms were caused by dust mites.  And yet, they had improved.  

So I absolutely believe honey worked for me but I have no idea why or how.

Gastric acid, B12, and Parietal Cells

The Second Brain goes delightfully deep into the regulatory signals involved in gastric acid production. .  The stomach is made up of several parts, which I am going to give diminutive summaries.  There’s the cardiac region (the heartburn prevention valve), the corpus (food storage area), the fundus (backup food storage, primary burp storage unit), and the pyloric antrum (home of actual digestion).  The cells that produce HCl (parietal cells) are in the corpus and fundus areas, where food sits and waits its turn to be digested.  This means they don’t have very good information about how much acid is needed.  Other parts of the body can send them information using three signals:  acetylcholine (source: vagus nerve), histamine (enterochromassin-like cells),  and gastrin (G cells).

Of these, gastrin appears to be the best understood.  G cells live in the pyloric (“digesty”) region of the stomach.  Based on a variety of signals, including pH and stimulation from the vagus nerve, they release gastrin to signal a variety of digestion-related cells to release that digestion is happening.  Parietal cells release gatric acid, chief cells release pepsinogen, the valve between the small and large intestine opens (to create room for new food), and the valve between the stomach and throat close (to prevent heartburn).

Those of us who once had allergies so bad they kept us home from school will remember histamine as the thing that simultaneously put us to sleep and created itching so painful we could not sleep through it.*  The digestive histamine is the same chemical, but is secreted within the stomach and so (I assume) does not risk what we classicly think of as an allergic reaction.**   Histamine is not so much a signal to produce gastric acid as the absence of histamine signals cells not to produce it, no matter what other signals they get.  Histamine is produced by Enterochromaffin-like cells, which are intermixed with the parietal cells (along with other enteroendocrine cells) in the corpus and fundus gastric regions.  ECL cells are stimulated to produce histamine via gastrin (the same gastrin that stimulates HCl production directly) and pituitary adenylate cyclase-activating peptide which, if I’m reading this correctly, can act as both a neurotransmitter and a hormone (which is rare but apparently not unheard of.  I will refer to this dual-purpose molecules as ballerina-astronaut messengers).  Dr. Internet is curiously silent on the topic of what cells release pituitary adenylate cyclase-activating peptide.  If it’s reaching G cells as a neurotransmitter it must be coming from the vagus nerve, but there may be other mechanisms as well.

Lastly there is directly nerve stimulation, coming from our friend the vagus nerve, delivered via third and more traditional neurotransmitter, acetylcholine.  So the inputs to the system appear to be signals from the digesting food, and a tiny wizard sending out electrical sparks via the vagus nerve.  This wizard can be encouraged to do so via things like chewing and thinking about food, but we do yet not understand his simple yet beautiful language.

Here’s the interesting things: the parietal cells that produce HCl also produce something called intrinsic factor, which preps vitamin B12 for digestion.  This is very, very rare.  Almost all cells in the body do exactly one thing.  These two things aren’t even related.  The Second Brain is a little vague on what stimulates intrinsic factor production: it says it uses the same signalling molecules as HCl, but not that they’re triggered by the same receptors, or that they react identically to the signal.  It’s the kind of vagueness that makes me think we don’t know for certain.

But it seemed plausible that they might be related, and thus the same factors that cause a gastric acid shortage could cause a B12 shortage.  I have a gastric acid shortage.  Could I have a B12 shortage?  I checked the symptoms: it’s a complete grab bag, because B12 is used for DNA synthesis and energy production, and there is no system that does not affect.  I pull out my last blood test results: B12 was high normal.  It’s seven months old, but there’s every reason to believe my B12 has gone up since then.

There are two categories of explanations for why I produce insufficient HCl:  either the signal to produce is not reaching my parietal cells, or my cells don’t react to the signal properly.  The signal to the parietal cells to release intrinsic factor seems to work thus fine.  If it’s the same signal (which I need to research more), this strongly suggests the problem lies inside the cell rather than in the signal.  This is disappointing because my “mumble mumble vagus nerve” hypothesis was both interesting and led to a pleasant treatment plan (keep up the sensory integration work aimed at my misophonia).   Now I will have to investigate the intracellular manufacture of HCl.

*”Us” is an optimistic term.  I am very rare in finding histamines fatiguing, and I sure hope very few people experienced allergic pain like I did.

**Nor do anti-histamines like Claritin, whose makers I once pledged my hypothetical firstborn child to, interfere with digestion.  Drugs marketed as anti-histamines act on only one of three possible histamine receptors (H1),  and it’s not the one you find in the stomach.  Drugs that affect that receptor (H2) are marketed as anti-heartburn medications.