Sunday, August 23, 2009

fMRI is not an inherently correlational method

If you open up your favorite cognitive neuroscience textbook it's very likely that you'll find it stated somewhere that "fmri is a correlational method". Indeed, you'll read that this is one of its major drawbacks. On the other hand, transcranial magnetic stimulation (TMS), you'll be told, is a tool with which one can make honest-to-god causal inferences. FMRI = correlational; TMS = causal. That will be on the test. You can bank on it.

I don't really even need citations for this; it's conventional wisdom. I mean, everybody knows that fMRI is a correlational method. Of course it is! The notion that fMRI might not be a correlational method is simply too absurd to contemplate.

If I did not occasionally want to say something slightly outlandish, however, I would not bother maintaining this (biannually updated) blog.

So here it goes. I am going to say something slightly outlandish. Get ready for it.

"fMRI is not an inherently correlational method".

Having made such a highly unorthodox and possibly even dangerous claim, I should probably back it up with an argument. First we need to define our terms.

What is a Correlational Method?

A correlational method is one that examines the relationship between two measured variables over which the investigator has no experimental control. For instance, a study that examines the relationship between dietary cholesterol and heart disease is correlational. The experimenter exerts no control over either of the two variables. Correlational methods do not allow for causal inference. Just because we observe a correlation between dietary cholesterol and heart disease does not mean it can be concluded that one causes the other. Thus, as we learned in Statistics 101, correlation does not imply causation.

What Permits Causal Inference?

If we want to say something about causality, then we need to conduct a true experiment. Experiments allow the scientist to manipulate one variable (the independent variable) while measuring another variable(s) (the dependent variable) while holding everything else constant. If the experiment is properly controlled -- which is is no easy thing, of course -- then any observed change in the dependent measure that is correlated with the experimental manipulation of interest is assumed to have been caused by that manipulation. Thus, under certain special circumstances -- i.e. when an independent variable is manipulated and experimental control is assured -- correlation does indeed imply causation.

Does fMRI Permit Causal Inference?

Having defined our terms, let us now address the question we set out to answer, namely: is fMRI a correlational method? Well, I must admit that fMRI seems awfully correlational at first blush. I mean, you put someone in a scanner and he presses buttons and looks at pictures and wiggles his toes and dozes off probably for a full third of the experiment -- and meanwhile you're capturing these images every couple of seconds that you then submit to a fancy correlational analysis which spits out colorful activation maps.... I will grant that it seems correlational.

Here's why it's not, though. An fMRI experiment generally speaking involves an independent variable that is manipulated by the experimenter and a dependent variable that is measured by the machine. The independent variable might be, for instance, whether the subject is viewing a face or a house; and the dependent variable is the blood-oxygenation-level-dependent (BOLD) imaging signal. If everything else except for the particular experimental variable of interest (face or house) is held constant, then such an fMRI paradigm constitutes, by definition, a True Experiment, and therefore permits of causal inference.

Causal Inference of What?

Perhaps I've engaged in a bit of sophistry. Sure, fMRI allows for causal inference of a kind, but it does not allow one to infer anything about the sorts of things one is actually interested in! Well, lets think about what one can infer with fMRI. You can always say (assuming reliable statistics and proper experimental control) that your experimental manipulation caused the change in brain activation, wherever it is found. So in our simple face-house experiment if we see more activity in the fusiform gyrus while subjects viewed faces we are free to say that this was caused by our experimental manipulation. Ditto if more activation were observed, say, in the cerebellum.

Of course, often we are interested in more than the simple relationship between a task manipulation and brain activity; rather, we are interested in some theoretical entity -- a "cognitive process", if you will -- that we hope to observe in action during the performance of a task that was expressly designed with that entity in mind. Putting aside the obvious problem that your pet cognitive process is almost certainly a figment of your imagination, it is highly likely that even the most subtle task manipulation will reliably prod in to action a whole lot of cognitive processes in addition to that particular one you set out to manipulate. In other words, if you want to make inferences about cognitive processes, rather than task manipulations, you are going to have a very tough time of it. But this not a problem peculiar to fMRI. It's just as big a problem for reaction time studies and eye-movement studies and any other method in cognitive science, including TMS.


What about TMS, anyway. Why is it that TMS is so widely assumed to be a "causal" method and fMRI a correlational one? In fMRI we can make a causal inference from task manipulation to a difference in brain activation. In TMS we can make a causal inference from brain manipulation to a difference in some behavioral measure. It's an epistemological wash. Both methods allow for causal inference, both are useful, and the two are in a certain sense complementary. All the issues relating to inferring something about "cognitive processes" are equally as problematic for TMS as they are for fMRI.

But what about inferences about the "necessity" of a given region for a given "process"? Isn't this where TMS shines?

Not really, for the exact same reasons fMRI falls on its face here. If I apply TMS stimulation to a brain region and observe a behavioral effect, I can only say the stimulation to region X affected behavior Y. Suppose stimulating region X in turn stimulates region Y which in turns stimulates region Z which in turn disrupts a cognitive process A which in turn leads to impaired performance on task B? Was the stimulated region "necessary" for the performance of the task? No, it was not. It may have merely set off a chain of events that lead to the excitation or depression of region Z -- the unsung, unknown necessary region in the sordid affair -- which eventually gave rise to the behavioral effect. The same sort of reasoning can be applied to fMRI activations, which are equally susceptible to the problem of indirect effects. It's easy to control the experimental environment with a task or magnetic stimulation, but it's real hard to control the brain.


So, TMS and fMRI are on more or less equal footing when it comes to the question of inferring whether a brain region is "necessary" for a task or not. This is not to say that the two methods do not potentially offer differing or complementary or even convergent evidence in support of this or that hypothesis of interest. On the contrary, I think the combining of fMRI and TMS is a very powerful approach. But I think the claim that TMS is "causal" and fMRI is "correlational" is -- unless someone can convince me otherwise -- wrong.