Tuesday, July 26, 2011

Exposing the Epipenomenon with TMS?

Nowadays it is proper for the neuroscientist to be slightly embarrassed and faintly apologetic about his or her fMRI researches. One should strike the same attitude about fMRI as one does about the British rock band Coldplay -- I know you like them, you know I like them, we all know we like Coldplay, but we're frankly a little bit ashamed about it. It is somehow tacky to like Coldplay.

There is a ready antidote for any researcher that wants to show everyone that he or she is not fooled by the easy listening schlock of fMRI, that he or she is a reluctant and skeptical user of that pretty little correlative toy. The ready antidote is transcranial magnetic stimulation -- TMS. TMS is tough. TMS is no-nonsense. TMS gets the job done -- and with no pictures. TMS tells you what is necessary, and it tells you about what is causal. And here's the kicker: TMS calls the bluff of fMRI, it holds fMRI to account, it cuts right through fMRI's bull. And TMS has nothing but contempt for Coldplay.

Here's how it often works with TMS. You've done a few fMRI studies and you keep showing that a region in the parietal lobe activates when subjects are engaged in a particular cognitive activity. It's not a one-off finding. You've used different paradigms and control conditions and this parietal area keeps popping up, it keeps stubbornly activating. You're a careful researcher. You've written the papers, you've presented the data at meetings, and your colleagues are impressed -- but not convinced. How do you know this region is "necessary" for the cognitive activity, they ask? How do you know it's not some sort of "epiphenomenon"? It's fMRI, after all.

At this point, you know what must be done. You know you have to zap your parietal area with TMS while subjects perform your paradigm. If you disrupt your parietal area with TMS and performance on the task suffers, then you've closed the loop. You've shown that your region is necessary, that it's causal, that it's for real, that it's not a stinking epiphenomenon. Case closed, The end.

That's the formula, that's the pattern, and that's how it usually unfolds. In other words, and somewhat paradoxically: TMS always has fMRI's back. TMS tells you what you thought you already knew. You never thought your parietal area was an "epiphenomenon", you thought it was doing something legitimately useful. Thanks for confirming for us what we already fervently believed, TMS!

But hang on. How come you never hear this story (this inferential pattern)?:

"After six fMRI studies implicating our parietal area in cognitive activity X, we performed a series of TMS studies designed to see whether our region was really necessary. The results showed no effect of TMS at the stimulation site during the critical task period, contrary to our expectations. We therefore conclude that activity in our parietal region is entirely epiphenomenal, and we begin our search anew for the neural basis of cognitive activity X".

Follow me here. If TMS is what we need to expose fMRI's empty and functionless epiphenomena for what they are -- technicolor gewgaws of no cognitive import -- then why are we never treated to hypothetical passages like the one quoted above? If we can't cite examples in the literature (perhaps such examples do exist, but I have just never come across them?), then it suggests that TMS, at least in the way it is being used, is not a really the no-nonsense tough guy we thought it was. Indeed, TMS is a rubber stamp for fMRI. You can can count on it never to expose an epiphenomenon. Don't worry, your epiphenomenon is safe with TMS.

Now, before you accuse me of being hard on TMS, let me say, I like TMS, I think it is a marvelous tool, I'm proud to call TMS a friend. But we need to consider why it rarely if ever exposes fMRI's ghoulish epiphenomena.

Reason #1. Exposing the epiphenomena involves proving the null. If zapping the parietal region has no effect on behavior, then the null hypothesis (e.g. epiphenomenon) is not rejected. The problem then is that conventional statistical inference is all about rejecting the null, and anything else is just a "negative finding". And negative findings are radically less likely to be published than positive ones. So, when it comes to exposing the epiphenomena, TMS has its hands tied. It couldn't expose an epiphenomenon even it wanted to -- it could only "fail to the reject the null hypothesis of an epiphenomenon". And who wants to do anything that sounds half as tedious as that?

Reason #2. One may speculate that fMRI epiphenomena (we're talking about replicable, reliable epiphenomena) are in point of fact pretty rare. In other words, if a region is reliably active during some cognitive paradigm, it's much more likely than not that the region is actually doing something functionally important, than that it is doing something useless and irrelevant to the task at hand. So when you zap the region with TMS, no surprise, performance tends to suffer.

Reason #3. Scientific orientation. Due to reason #1, you have to try pretty hard to expose an epiphenomenon with TMS. You have to be gunning for it. You're probably going to have to use unconventional Bayesian statistics to prove the null. How many researchers have undertaken a TMS study with the a priori hypothesis that the region that they were stimulating is only epiphenomenally involved in the cognitive activity required to perform the task at hand? Not many, I'd venture to say.

To sum up, I think TMS is a wonderful tool, and there is some first rate TMS research going on. The future is bright for TMS. But is it an fMRI "epiphenomenon-killer"? It doesn't seem to be. This is because killing an epiphenomenon requires proving the null; because epiphenomena maybe aren't that prevalent or at any rate clear-cut to begin with; and because if you really want to be an epiphenomenon hunter, you have to want it in earnest. You're gonna have to get all Bayesian if at the end of the day you want to be standing triumphantly atop a giant epiphenomenal carcass, with your TMS spear stuck deep in its epiphenomenal guts.