Voodoo in the brain

I'm sure you've heard about the placebo effect, but have you heard of the nocebo effect?

If you know a little Latin, you can guess what it means.  Placebo is Latin for "I will please;" nocebo for "I will harm."  The nocebo effect occurs when you expect something to cause you unpleasant symptoms, and even though what you've consumed is harmless, you experience the symptoms anyhow.

We've known about the nocebo effect for some time.  It gained prominence due to investigations of "voodoo curses," where someone was cursed through a voodoo ritual, and lo and behold, the cursed individual sickens and dies.  Skeptical researchers don't credit this with voodoo actually working; they have come to realize that when a person thinks they're going to become ill, perhaps even die, the expected outcome manifests in the body.

[image courtesy of photographer Marie-Lan Nguyen and the Wikimedia Commons]

A recent study gives us an even better lens into the nocebo effect, and how the brain influences health.  Any medical researcher will tell you that people in clinical trials of medications will often stop taking the pills they were given, usually citing unacceptable side effects.  What is less well known is that a substantial fraction of the people who end up dropping out of the trial actually were receiving an inert substance.

So the control group, in other words.  They were taking a sugar pill, but because they expected to have side effects from the medication, they went ahead and had side effects anyhow.

The most recent study, which was published in Science last week, was the work of four researchers at the University Medical Center of Hamburg, the University of Colorado, and Cambridge University, and had the unwieldy title, "Interactions Between Brain and Spinal cord Mediate Value Effects in Nocebo Hyperalgesia," and it had a fascinating result:

People in the control group of pharmaceutical clinical trials are more likely to have spurious unpleasant side effects if they're told the medication is expensive than if they're told it's cheap.

Furthermore, they have pinpointed the areas in the brain that are responsible for the foul-up.  The authors write:

Value information about a drug, such as the price tag, can strongly affect its therapeutic effect.  We discovered that value information influences adverse treatment outcomes in humans even in the absence of an active substance.  Labeling an inert treatment as expensive medication led to stronger nocebo hyperalgesia [negative side effects] than labeling it as cheap medication.  This effect was mediated by neural interactions between cortex, brainstem, and spinal cord.  In particular, activity in the prefrontal cortex mediated the effect of value on nocebo hyperalgesia.  Value furthermore modulated coupling between prefrontal areas, brainstem, and spinal cord, which might represent a flexible mechanism through which higher-cognitive representations, such as value, can modulate early pain processing.

Which is kind of amazing.  People who experience unexpected side effects are often labeled as hypochondriacs -- i.e., that they know perfectly well they feel fine, and are making up or exaggerating their symptoms out of fear or a desire for attention.  What's really happening appears to be far subtler.  Because of an expectation of harm, the brain actually manifests the symptoms the person feels they're likely to have.  Labeling the medication as expensive increases the subject's sense of having put something unusual into their bodies, resulting in more anxiety and worse side effects.

For me, the most interesting thing about this is the interaction of the brainstem and spinal cord, two parts of the central nervous system that are usually regarded as controlling completely involuntary responses, with the prefrontal cortex, often considered the most advanced part of the human brain -- the part that is associated with reasoning, decision making, and logic.  The fact that a freakout (to use the scientific terminology) in the prefrontal cortex activates a response in the brainstem is astonishing -- and also explains why people who experience the nocebo effect can manifest actual measurable medical symptoms.

And why some of them die.

All of which brings home once again how incredibly complex the brain is.  We're living at an exciting time -- the point where we're finally beginning to understand the thing in our heads that artificial intelligence pioneer Marvin Minsky called a "three-pound meat machine."  And, apparently, how easy it is for the machine to get fooled.  Kind of humbling, that.

Seeds of doubt

C'mon, people, it's time to grow up a little.

When we're toddlers, we accept things without question.  If our parents say something, we pretty much believe that it must be true.  (Whether we do what they tell us afterwards, though, is another issue.)  After a time, we start experimenting, and testing the world -- sometimes with unfortunate results, such as when we decide to find out why Mommy says that Mr. Finger and Mr. LightSocket can't be friends.

But this highlights an important principle, which is that our first and best way to find out about things is by finding evidence.  "Show me why" is a pretty important first step to knowledge.

It's not the last step, though.  After the "show me why" stage we should move on to "but how do you know it's true?", which is a deeper and more sophisticated question.  Okay, from the evidence of my eyes, it looks like the Sun is moving across the sky.  In order to move past that to the correct explanation, we have to ask the question, "What if there is a better explanation that still accounts for all of the evidence?"

And in this case, of course, it turns out that there is.

There are other facets to this mode of inquiry.  What confounding factors could there be?  What if there are uncontrolled variables?  What if the person who made the original claim was lying?  What if my preconceived biases made me misjudge the evidence, or (perhaps) ignore some of the evidence entirely?  What if there is correlation between A and B, but instead of A causing B, B causes A -- or, perhaps, some third factor caused them both?

This whole process is what is collectively known as "Critical Thinking."  What is unfortunate, though, is that a lot of people seem to be stuck at the "I see evidence, so it must be true" stage, which is probably why the whole WiFi-kills-plants thing is making the rounds of social media... again.  Just a couple of days ago, a friend of mine ran across it, and asked the right question: "can this actually be true?"

The claim is that five ninth-graders from Denmark had noticed that if they slept near their WiFi routers, they "had trouble concentrating in school the next day."  Because clearly, if ninth graders are distracted, it must be because of WiFi.  So the kids allegedly set up an experiment with cress seeds, placed some near a router, and had others in a "room without radiation," and had the results pictured above.

Well.  The whole thing is suspect from the get-go, because we're told nothing about other conditions the seeds were experiencing -- light, humidity, temperature, air flow, and so forth.  Was the "room without radiation" well-lit?  Were the seeds near the router warmer than the supposed control group?  There are a hundred things about this so-called experiment that we're not being told, and yet we're supposed to buy the results -- in spite of the fact that "control all variables but one, or the results are suspect" is the first thing taught in high school science classes.  (For a nice take-apart of this "experiment," take a look here -- and note, especially, that attempts to replicate the girls' experiment have not produced any results.)

What else?  First, it's from Spirit Science, a notorious peddler of woo.  Second, unless they were in a lead-lined vault, I doubt whether the control seeds were actually in a "room without radiation."  Even if you're some distance from the nearest router, you (and your room) are constantly being pierced by radio waves, which pass easily through most solid objects (if they didn't, old-fashioned (i.e. pre-cable) televisions and almost all modern radios would not work inside houses or cars).  Then there's the issue of how many thousands of WiFi routers in the world are sitting near perfectly healthy house plants -- for years, not just for thirteen days.  And even if WiFi did kill cress seeds, there's no guarantee that it would have the same (or any) effect on humans.  Don't believe me?  Go for a nice swim in the ocean, and then pour a cup of seawater on your marigolds, and see if the results are the same.  (In all seriousness, researchers face this all the time when developing medications -- therapies that work well in vitro or on lab animals might have different effects on human subjects.)

So to the people who are unquestioningly passing this around, just stop.  Exercise something past the You-Showed-Me-A-Picture-So-It's-True level of critical thinking.  If you see something that seems suspect, ask someone who might know the answer (as my friend did with this claim).  Or, in this day of information accessibility, you could simply Google "cress seeds WiFi experiment debunked" and you'll find everything you needed to know.

We all were toddlers once, and no harm done, unless you count unfortunate encounters with light sockets.  But let's exercise a little higher-level thinking, here, and not just accept whatever comes down the pike.