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.

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.

Conclusion

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.

10 comments:

  1. fMRI is correlational. Task modifications are causal. Brain changes that correlate with causal task modifications are interpreted as the result of said changes. Or the result of the result of said changes.

    However, you cannot tell whether the changes in activation you find are the result of your changed task, changed strategy, changed response, or changes in non-task activation (dozing off for half the task instead of one third, because it is more boring).

    With TMS, if you apply task manipulation A, then observe activation B, disrupt area Y, and no longer find behavior Z (but still B), it will inform you that Y is not required for B, but is required for Z. If you found neither activation B nor behavior Z, this would mean that Y -> BZ.

    Of course you can make causal inferences in fMRI using clever designs, and with analyses such as Dynamic Causal Modelling, but that does not render the method itself any less correlational. Your task manipulation plays a causal role, and perhaps the neural activity that you also observe does, but the fMRI does not.

    This is where TMS differs. Your task does not have to actively cause changes (though it can), the method itself does.

    Still, you are correct in saying that you can infer causal relationships using carefully designed fMRI experiments and analyses, and you can do TMS experiment that will not shed any light on causation.

    Basically, TMS allows you to tell that the region you stimulate is ‘somewhere upstream’ from the behavioral difference you find, whereas fMRI allows you to tell that the region you measure is ‘somewhere downstream’ of the difference you cause.

    ReplyDelete
  2. Hi Jasper,

    thanks for the comment.

    You say: "fMRI is correlational. Task modifications are causal". If we view fMRI as a way of measuring the brain over time -- a dependent variable -- it doesn't really make sense to state categorically that it is "correlational" -- correlational with what? It takes two variables to tango.

    Moreover, if task modifications (as you say) are causal, then task modifications with fMRI are also causal.

    It's true that changes in activation might be results of changed task, changed strategy,subject fatigue, etc. -- but this has nothing to do with fMRI per se, this is true of all psychological experiments, including reaction time, eye-tracking, EEG, TMS, and so on. Nobody, however, says that reaction time experiments are inherently correlational.

    The factors you refer to are mitigated by randomization of conditions and other methods of experimental control. True causal inference requires experimental control, of course, but this is a concern for all types of experiments, not just fMRI.

    so, while it was a nice effort, you have not succeeded in persuading me that fMRI is a fundamentally correlational method!

    Brad

    ReplyDelete
  3. I agree that strictly speaking fMRI is not correlational. If we take a behavioral point of view however I do think that fMRI can not tell us anything but correlations. A behavior scientists is not interested in which brains areas are activated by a cognitive task, but in which brain ares produce certain behavior. In other words, from the point of view of a behavioral science, a research method should use a dependent variable which measures behavior manifestations (RT, accuracy rate, eye fixations, test scores, etc) in order to reveal meaningful causal relationships. To put it simply, behavioral sciences are interested only in the brain->behavior direction of the possible causal relations between these two entities. Perhaps brain scientists are interested in the other direction as well. I personally cannot understand why it would be interesting to know that a cognitive process activates certain brain areas if we assume that the reverse is not true. It is only interesting if we assume that the relation is bidirectional and we cannot make such conclusions using fMRI.

    ReplyDelete
  4. This comment has been removed by the author.

    ReplyDelete
  5. Isn't it simply the case that TMS is an interventional technique, while fMRI is a measurement technique ? What am I missing ?

    ReplyDelete
  6. @MadScientist

    you'll have to define "interventional technique" for me. FMRI frequently involves an experimental intervention.

    ReplyDelete
  7. fMRI, like EEG, is not the means of the intervention, it is used to measure the effects of interventions (task instructions, drugs, what have you). TMS, on the other hand, is not used to make measurements, but to cause an intervention (by itself, or along with others) whose effects are then measured separately (reaction time, or perceptual accuracy, or even fMRI/EEG).

    ReplyDelete
  8. @MadScientist,

    It's true that the machine itself is not the physical cause of the intervention, but it's a distinction without a difference as it relates to the ability to make a causal inferences.

    ReplyDelete
  9. I was responding more to the comment than to your article itself...I agree with you and like your post.

    ReplyDelete
  10. Excellent post. I want to thank you for this informative read, I really appreciate sharing this great post. Keep up your work…
    transcranial magnetic stimulation therapy

    ReplyDelete