Friday, July 8, 2016

Faulty cluster-wise inference: Laughter and the 40,000 fMRI papers

Cluster Failure 

In a paper entitled: "Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates", Eklund, Nichols, and Knutsson (2016) show that several popular statistical packages for fMRI analysis have a strong tendency to find activation where there is, well, none. This is like the old "dead salmon" study, but with a lot more rigor, and a lot fewer laughs. At one point the authors estimate that 40,000 fMRI papers (since revised) might be invalid, noting dryly that it is "not feasible to redo them". Would we want to redo them if it was feasible?

Imagine a World ...

Imagine a world where it was feasible to redo 40,000 fMRI studies in about six-months, for around 50 million US dollars (a tiny fraction of the original cost of the studies). Four hundred MRI scanners, arrayed in hedge-like rows on an abandoned crop-field in Kansas, operated round the clock by experienced MR-technicians, and a huge pool of willing participants: old or young, consented, metal-free, and ready to perform a task of some gentle soul's devising (n-back, Stroop, or something more exotic). A cadre of crack Eprime coders (making $15 bucks an hour) will work round the clock to create accurate facsimiles of some 40,000 psychological tasks.

With the help of an extremely generous gift from a major MRI manufacturer and by being ultra-efficient, the six month timeline seems genuinely realistic in this alternative universe. We just need to run 220 studies per day for 180 days, which means we would need to scan approximately 4400 subjects per day or 11 subjects per-scanner per-day. Don't get me wrong, it's a lot of work, but it could be done (in the hypothetical universe that I have constructed for the very purpose).

The data would be analyzed on Google cloud-based servers (thanks to Google for their hypothetical support; Amazon passed) using an ultra-powerful 100,000 core computing cluster with AFNI's latest version (AFNI is really fast), and an updated version of the somewhat maligned 3dClustSim--which we understand has fixed the optimistic p-value bias. An automated report generator will check the results against the original finding and create a pdf addendum that will be linked to the original article's DOI and will show up in PubMed searches. If there is a replication failure, the paper will be automatically retracted, per agreement with a consortium of participating editors of neuroimaging-related journals, and replaced only with the addendum. Think of it: the sound of 20,000 fMRI papers being retracted. Some laughter, but a lot more crying. A fair amount of personal and scientific chaos is sure to ensue.

This can be done. Even with all the infrastructure, the 400 scanners, the compute servers, the MR-technicians, however, it will be hard work. But it's no moon landing, it's not rocket science (as they say), it's more or less routine, busy work--coding, scheduling, scanning, data crunching. Moreover, fifty million dollars is comparatively trivial, the cost of perhaps 50 small RO1 grants from NIH. Remember, the original research cost billions of dollars (according to my R terminal which prints out a large number in scientific notation:  4e+08 -- Billions, right?).

Would you fund my proposal? Would I fund my own proposal? Surely the modest effort to replicate 40,000 studies would be worth it, right? But it's not for me to decide. We need to ask the funding agencies, our peers, etc.

One critique we might face is, simply, that the work is not novel. Lack of novelty is the bete noire of many a hardened and unimaginative reviewer. Multiply this lack of novelty by 40,000 and we probably have a triage situation on our hands. No, definitely triaged. Indeed, R1 almost certainly writes as follows in a farrago of Trumpian emptiness: "Lacks novelty, not feasible, over-ambitious, fails to make a case for impact, power analyses not provided. Investigator is strong, kudos".

While it is true that R1 skimmed the grant on a turbulent United Airlines flight and just went ahead and submitted his usual boilerplate, in this particular case I happen to agree with him (everything but the "over-ambitious" part -- we can do this!). Let me repeat: I broadly agree with R1's negative assessment. The thing is, something doesn't sit right with me about my proposal. Would it perchance be a gigantic waste of time?

A Gigantic Waste of Time

Let me tread carefully here, since I am an fMRI researcher, and I believe that it's a very powerful and useful tool and that it has revolutionized neuroscience. With that said, I would not argue with anyone who said that the vast majority of fMRI-based science is not mission-critical to the immediate survival of the species. 

Put another way: lives are probably not at stake because of an fMRI study conducted in 2002 reported activation in the amygdala with an invalid significance cut-off. With fMRI and the neuroscience that uses it, it's more about the long haul, about accumulating evidence, about inching ones way forward along a variety of complicated scientific paths, full of false starts, blind alleys, and the odd crawl-hole that takes us to a new place. And make no mistake: evidence is accumulating from research using fMRI, and it is doing so rapidly, but rarely on the basis of a single study.

Pick 10 fMRI studies at random from a Pubmed search. Ask yourself, seriously. Does this study need to be redone and checked for validity by recreating the data on an abandoned crop field in Kansas with 400 simultaneously running MRI-scanners? The answer in 9 out of 10 cases will be a curt: "no". Even if if you think the result is false or suspect, the answer is very likely still "no", because, you know, why bother?

Ask yourself a second question. Would you rather the paper stays in the record somewhere or that it be summarily retracted if it were shown to have used a faulty p-value correction method? Before you answer, I want to discuss the value of eating your own dog food.

Eating One's Own Dog Food

In fMRI's adolescence (and PET's menopausal years), a curious thing started happening. Researchers started data-mining the published coordinate tables (so-called "Talairach coordinates") and doing ad-hoc and, later, quantitative meta-analyses of the data. These "coordinate-based meta-analyses" became very popular and as of today a Pubmed search indicates that at least 273 of these meta-analyses have been published. Even I published one. The 40,000 fMRI studies that we might, in our most draconian moods, like to have retracted like so many wayward social-priming psychology experiments, is the very stuff these meta-analyses are constructed out of.

And have you seen Neurosynth? This is a marvel of the modern world: it takes in the worst of the fMRI trash (many of the 40,000 are in there, I promise) and churns out very valid-looking meta-analytic results. Neurosynth thrives on weak effects that can be pooled together to produce a reliable result. It's like a mortgage-backed security for neuroscientists, without the financial crash. The reality is that if you take away the 40,000, you deliver a severe blow to Neurosynth. These studies are the dog food, and Neurosynth is one of its most advanced and effective eaters. It devours the stuff by the hundred. Neurosynth has evolved to such an extent that it easts the dog food, the cat food, the hamster food, the reeking offal on the butcher shop floor-- and, yes, even the caviar if it's in there too

Single fMRI Studies Rarely Matter, Except when they Do

Let me suggest that there is a kind of unwritten law in the fMRI-based research. If a study matters, it will very likely be followed up on. It may not be replicated exactly, but it will be followed up on. A study that matters launches a new "mini-paradigm" and a lot of researchers investigate similar questions with similar methods. These mini-paradigms beget a lot of publications, and then a lot of meta-analyses, and then Neurosynth gobbles up their coordinate tables, paying no attention whatsoever to their method of p-value construction, whether cluster-based, false-discovery-rated, uncorrected--whatever. It's just dog food and Neurosynth eats it.

A paper that matters, is one that starts a new mini-paradigm. I define "matter" purely in the social sense of "generating research". The studies that matter are a tiny minority of the total worldwide fMRI research output. Let me be clear, a study could be rather poor as a scientific exemplar and yet still "matter". Likewise, a very good fMRI study could be published and then, sadly, die on the vine. It doesn't matter (for now at least). Sometimes a study is even published in Science or Nature, and immediately consigned to the sorry state of not mattering.

Now, if a study is not having an impact, if a study doesn't matter in this limited sense--it's not generating research, nobody is using the paradigm, etc., do we need to redo the work? Why? Suppose the original result was overturned by our Kansas MRI fleet? What of it?

Yes, someone will be embarrassed, but what else? Fortunately--or unfortunately as the case may be--the vast majority of the 40,000 potentially invalid studies belong to this lot. It's simply not a matter of urgency to redo much of this work; and it might even be actively harmful if these studies were removed from the scientific record.

There is another category of papers, however. These are studies that generate a lot of interest and spawn much new research in one way or another but are never followed up on, let alone directly replicated. These are one-offs. You don't find them in meta-analyses, they are as it were paradigmatic loaners with outsized influence. There are perhaps no more than 100 examples of this category in the history of fMRI-PET research. And let me tell you something. Forget our methodological difficulties with cluster-based p-values and false-positive rates and the idea of "redoing 40,000 studies". Forget all that. Because if we can't even muster the energy to replicate a handful of major "one-off" studies with hundreds of citations and a major influence of the field--how are we going to replicate the innumerable ignored and ignorable fMRI-dregs that are cited twice a decade? The issue isn't p-values, it's the will to replicate, i.e. that there's very little of it

 Quick, name three major fMRI replication attempts of high-impact studies that have not been "followed up on" in the above sense? I'll even throw you a bone. Now you only have to name two.

Modest Goal for fMRI-research: Replicate 100 High-Impact (Non-Replicated) Studies

We don't need 400 scanners on a crop-field in Kansas running round the clock. We could get by with five. I'm only asking for five scanners ! (R1: "The Budget is reasonable"). The goal is to replicate the top 100 most influential fMRI studies that have not been directly replicated or otherwise meta-analyzed to death. We do not need to replicate the "n-back" task because once in 1998 somebody used a faulty p-threshold. We're looking for special papers, with special influence, that have never been replicated. It doesn't matter what analysis package or p-value method they used.

The top 100 studies will be determined by a consensus process resulting in a rank-ordered list. We might use graph theory, hubs and all that. Power analyses will be painstakingly carried out for each of the 100 studies. We will still petition Google and Amazon for the 100,000-core server, even it will frankly be overkill. We will not request any "retractions" of the original work in the case of a replication failure, and we will of course place the resulting fMRI data in something eminently accessible, like OpenFMRI.

R1: "The project is novel and innovative and seems quite feasible. This reviewer, for one, appreciates the detailed power analyses. The investigator is strong. I only have a few nitpicks (detailed below) but these are very minor. Overall, a very strong proposal."

Wednesday, February 4, 2015

The Critic as a Scientist: A Dialogue on Incremental Science

A DIALOGUE. Persons: Gilbert and Ernest. Scene: Gilbert's Office, University building, 4th floor.

ERNEST (knocking gently): Gilbert? Do you have a moment? May I come in for a brief chat?

GILBERT: Of course, come in Ernest! How are things going? What's on your mind?

ERNEST: Well, it's about my proposal  ...  the one you were going to look over. Have you had a chance?  I mean, to read it?

GILBERT: Indeed. Your proposal. Right. Rather hefty tome, wasn't it?  Let me see here. The one on X-Ray crystallography of owl pellets in urban parks?

ERNEST: No, not that one. That is not my area of interest. If I may refresh your memory, it was the one about computational modeling of the skunk olfactory system using deep belief networks.

GILBERT: Ah yes, of course! I did have a look at your proposal last weekend I believe it was. Curled up to it on an eve with a cup of Earl Grey and the Kardashians on the telly.

ERNEST: And? What did you think? I think it's quite far-ranging, quite exciting!

GILBERT: Appalling family. Simply appalling my dear fellow Ernest. The Kardashians, what has gotten in to --

ERNEST: no -- I mean my proposal, not the ... Kardashians.

GILBERT: Ah yes, quite so! Your proposal. Here's the thing. And I want you to take this in the intended spirit as, you know, constructive and all that. A young scientist's psyche is a tender thing and one must be careful about these matters.

ERNEST: Oh! Of course. That's why I came to you, out of all the people in our department, it's your critical faculty, your experience, your ability to get right at the heart of the matter. Everyone told me you're the one I should talk to, that you're  a "straight shooter" and so on.

GILBERT: Well, I don't know about that. I'm adequate. I have read many a grant proposal, I will say that. Now. About your little effort. My impression -- and let me say that I am not completely familiar with the skunk olfactory system, and so forth -- but my overall impression was that the work you propose, and I mean no offense here, is a tad, how shall I put it, incremental.

ERNEST: Well, do you really mean it? So you think my work will advance the field!? This is wonderful coming from someone with such experience, such a sharp and probing critic ... I don't know what to say, I could not have hoped for such a validation of my work at this stage in my career!

GILBERT: Uh, yes, well. Ernest. I think perhaps you have misunderstood me. That is to say, I do not think that my comment can necessarily be taken quite so ... positively.

ERNEST: Whatever can you mean, does my work not advance the field?

GILBERT: Yes, it does. Certainly. Excellent studies, careful work, well-controlled, and so forth. But you're playing small ball. You're advancing the ball, but barely two yards. Three at best. Right up the middle in a great pile-up. The punter is already warming up. It's, as I say, incremental.

ERNEST: But surely this is how science progresses, in small steps, is it not? Small accumulations, little advances, we chip away at the unknown, with our little tools, our chisels and picks, scraping off one layer at a time. Nature is miserly with her secrets, and we cannot expect to simply knock down her door in an uncouth and greedy rampage, we must approach her with guile and care, craft and painstaking diligence!

GILBERT: That is a fine sentiment, Ernest. Marvellously quaint. But, it doesn't work like that. Not in this funding climate, anyway.

You don't want these baby steps. No one wants that anymore. They want leaps, big leaps. Triple jumps, you know. Great strides, long bombs. You have to throw the ball down field. Deep down field. Who was the chap? Evil Knievel, jumped his blasted motorbike over the Grand Canyon -- now that was daring! You must conduct experiments that only a fool would think could possibly succeed but once in 20 times.

ERNEST: But a leap is itself an increment, so I don't quite follow here. I fail to see how you are quantifying increment here. What is the scale? What are the units?

GILBERT: Ernest, don't be such a bore. Take for instance my own work. If I may? I hope you don't find me conceited. My work on the iridescence of polar bear pelts in arctic climes is clearly an example of research that moves the field. And when I say "move", I don't mean little itty-bitty steps, tiny eency-weency increments. No. I mean giant steps. No, not even steps. Because a step implies that both feet are on the ground at some point. Right? I mean, we know this from Olympic speed-walking competitions. They hand out penalties for skipping, or whatever they call it. But I digress. Where was I? Yes. My work. I hope you don't mind if I avail myself of a sports metaphor?

ERNEST: By all means.

GILBERT: Well, my own work reminds me a little bit of when Michael Jordan -- shall I call him M.J.? [Ernest Nods] -- er, it reminds me of when M.J. triumphed in the great the dunk contest in 1985 in Chicago. Do you remember in what fashion he won that epic event?

ERNEST: Oh yes, I'm a big basketball fan, yes it was marvellous! The dunk from the free throw line, I assume you mean?

GILBERT: Exactly! He started way back at the far end of the court, in a lovely little saunter, and then accelerated with that long graceful body down the full length of the court and then he did it! With foot planted from on the free throw line he took off and soared, sharking his way through the air, lifting higher and higher, his tongue wagging, cameras flashing all over the arena -- and then he threw it down! To thunderous applause! It was ... sublime, a gorgeous combination of beauty and athletic grace that hinted at a higher aesthetic, the numinous, of an exalted state of consciousness that is only occasionally glimpsed from amid the dull quotidiana that fills our lives here on earth ... Yes! This is what my research is like! It is the very personification of my scientific work!

ERNEST: Of course. Gilbert, your research on the reflective properties of the polar bear fur is known everywhere, I have heard. It is brilliant, everybody acknowledges that. It is inspiring work, perhaps even "Jordanesque". But, if I may? Your example is perhaps not entirely apt.


ERNEST: That is, as an example of a "non-incremental" achievement, it is not quite apt.

GILBERT: How so, my dear Ernest?

ERNEST: Why don't you know? It was Julius Erving, "Dr. J." that pioneered the dunk from the free throw line. Only Dr. J. did it first in 1976 in the ABA dunk contest to much fanfare. Moreover, he repeated the feat in the 1984 NBA dunk contest as an aging veteran in his legendary showdown with Larry Nance in the final round.

GILBERT: Ah yes, of course. It slipped my mind. It is true that Dr. J. was something of a forerunner here. But to call M.J.'s version of the free throw line dunk "incremental" is nothing short of absurd. For one, Dr. J. ran with the ball, whereas Michael dribbled the ball the full length of the court, and ...

ERNEST [interrupting]: Seems rather incremental.

GILBERT: ... Michael did that little -- that little -- how should I call it, that little "pump" with the ball. A wonderful little accent, so stylish, so perfect! Here, see for yourself, it's easy to find on YouTube.  

ERNEST: You have no argument from me that it was an exquisite dunk. But nevertheless an incremental advance over Dr. J's effort. In my opinion. Indeed, there is something about Dr. J's dunk, it's very spareness, its unadorned beauty, the austerity, the grace. It was Homer's Iliad to M.J.s Johnny-come-lately Aeneid. It seems to me that Jordan dressed up Dr. J.'s perfect dunk with unnecessary ornamentation, curlicued mannerism, topping it off with some rather superfluous hip-hop preening and face-making.

GILBERT: You may have a point my dear Ernest, but if I may paraphrase the great Argentinian author Borges -- or  Bor-hace as they call him in his native land -- great men create their own precursors. You are being too literal with chronology here Ernest, as far as I am concerned the free throw line is entirely MJ's, notwithstanding the rather primitive earlier effort by Dr. J.

Let me tell you a story about another doctor, Dr. J. Winston Finch, a zoologist of the mid 20th century who made many important observations on plant and animal life in the arctic. Finch, as it happens, penned some rather incisive remarks on the reflective aspects of the polar bear coat that he would include in a footnote of an article that was published in an esoteric Soviet zoological journal in the early 1950s. I cannot recall how I came into possession of this work, only that I went to considerable effort to have it translated from the original (and, I might add horribly, broken) Russian in which it was written. What I found in the footnote was to change my life forever, as it contained an almost fully-formed theory of polar bear fur-reflectance, replete with mathematical formulae and several rather ingenious hypotheses about the evolutionary provenance of the polar bear's white coat. In a fever of work over the summer of 1967 I turned Finch's footnote into a robust work of science and, later that year when my effort was published in Nature Arctic, would make me famous in zoological circles the world over. And how far had I really gone beyond the ideas contained in Dr. Finch's obscure footnote? Not far, to be honest. I dressed it up, repackaged it. If you will, Ernest, I added a my little "pump" move, where he ran, I dribbled. Still it was a quantum of difference that would change my life forever.

ERNEST: A "quantum"?

GILBERT: You are too literal my friend. It was a quantum leap in the metaphorical sense. If you prefer it was a thousand leagues, a dozen light years, over the moon and then some. His footnote was utterly forgettable, my paper and the work that would follow is an imperishable monument to science.

ERNEST: And what became of Finch?

GILBERT: He died in utter penury of Syphilis in an Igloo in 1972. His notes indicate that he was still working, that he had become fanatically (and fatally) obsessed with the red-throated loon, but had almost completely lost his wits. It seems that the many years he spent in the harsh arctic climate had taken a toll on him. He was an indefatigable seeker of truth, a scientist to the core, but was not successful in the career-sense that is so important to us these days.

ERNEST: That is tragic!

GILBERT: It is a cautionary tale. His work was, of course, irremediably incremental. He plugged away, year after year. He did publish from time to time, but his work did not garner attention, and his shoe-string budget was a thing of necessity, as the funding agencies had little appreciation for his brand of painstaking science.

ERNEST: And yet you have succeeded where he failed.

GILBERT: And, what's more, without having ever set foot in a cold climate for the purpose of field work. Field work! It reeks of incrementalism, of course. Yes, where Dr. Finch toiled, I shined in the reflected light of acclaim and admiration. My popular books sold by the hundreds, my scientific researches thrived. While he was logging his data and making those absurdly minute little observations, I was dreaming up big ideas, giving keynotes in front of giant crowds, taking risks, daring to outstrip the "frontiers of science". That has made all the difference, my dear Ernest.

ERNEST: I think I see where you're coming from. I must avoid the awful fate of Dr. Finch, I can imagine him shivering in that Igloo, frost-bitten hands, with that awful little journal, the song of the red-throated loon worming around his head like some dread and haunting hallucination. It is too horrifying to contemplate.

GILBERT: Earnest, I am glad that I have made some impression on you. I do not wish to make you ill at ease. I do think that you have a modicum of talent. I believe you could eek out a career at this University, perhaps even become a full professor some day. However, Ernest, I think I may offer you a last bit of advice. It's about the skunk. Well, I think you should stop studying it. You need to part ways with the skunk.

ERNEST: But whatever for? I have devoted my career to the study of the skunk's olfactory system: it is one of nature's most fascinating puzzles. It is an exquisitely sensitive organ that has evolved to tolerate the sulphurous musk that it uses to repel would-be attackers. ...

GILBERT: But Ernest, lets be honest, it's an appalling creature. Perfectly appalling. You're never going to get anywhere with the skunk. Not in this funding climate. Vicious little creatures with a hideous stench. Look at the polar bear, for instance. Noble. Majestic. It lords over the arctic tundra with power and panache. 

Why don't you study ... the Galago? Galago's are all the rage right now. There were three Galago Science papers in the last three months! Galago's are just phenomenally sexy right row.

ERNEST: What do I know about Galagos? Nothing! Well, I do know this: their olfactory systems are utterly pedestrian. There is simply no there there. Galago, do you really mean it?

GILBERT: I do Ernest. I do. You may take my career advice, or not. Perhaps you view me as some sort of pompous avuncular brute that is overstepping his bounds. I don't mind. But Ernest, I do very much want you to succeed, is all. Do look in to it. Charming little creatures, Galagos, with those large, flashing eyes!  I think you'll thrive with the Galago, I really do.  You're a quick study I understand. Take the plunge. Bury yourself in the library for a few weeks, you'll emerge a Galago expert, I know it!

ERNEST: Do you think so? OK, I will. I'll do it, I'll consider it very seriously at least. I do want to succeed. If I need to switch fields I will.

GILBERT: That's the spirit!

ERNEST. Thank you, Gilbert, this has been very helpful. I'm glad I knocked on your door.

GILBERT: Oh, any time.

ERNEST: Shall I see you at the Faculty Club some time?

GILBERT: Of course! Um .. and Ernest. About Dr. Finch and you know ... the footnote. Please do let us keep that between us. Shall we? It was a bit of an unguarded moment. To be perfectly honest, I have never told a soul about that. I hope you understand...

ERNEST: Of course, I will take it to the grave!

GILBERT: Wonderful!

ERNEST: Bye now!

Friday, August 15, 2014

Guilty Brains

In a well-known paper on the role of neuroscience in the court, law professor of Stephen J. Morse opens with the following paragraph:
Brains do not commit crimes; people commit crimes. This conclusion should be self-evident, but, infected and inflamed by stunning advances in our understanding of the brain, advocates all too often make moral and legal claims that the new neuroscience does not entail and cannot sustain. Particular brain findings are thought to lead inevitably to moral or legal conclusions. Brains are blamed for offenses; agency and responsibility disappear from the legal landscape.

         From: Brain Overclaim Syndrome and Criminal Responsibility: A Diagnostic Note
         Public Law and Legal Theory Research Paper Series Research Paper No. #06-35 

Professor Morse is of course punning on the famous line often used in defence of gun rights in America, namely, "Guns don't kill people, people do". This guns rights slogan has the virtue of at least being literally true. No, guns don't kill people; guns just make it enormously easier to do so. Guns are exceptionally efficient facilitators of death. Of course, as an argument in favor of gun rights, it's fatuous. For instance, you never hear anyone say: Atomic bombs don't annihilate populations, people do. Or, how about: weaponized Anthrax doesn't kill people, people do.

But lets return to Morse's line about brains. "Brains don't commit crimes, people do". I confess, I'm a neuroscientist and not a legal scholar, but something seems amiss about this one. Is there kind of logical fallacy lurking about in that line? If the fallacy doesn't jump out at you, maybe the following mini-vignettes will help clarify what I'm talking about.

What is a person? Maybe there is a legal definition, but lets forget that for a moment. Lets say for now that we know a person when we see one. Below are the stories of Joe, Mike, Jim, Jake, and Jack.

"Hey, look at that person over there. Yeah, the guy riding the bike. Nice person. Friendly fellow. His name's Joe." Joe has a head, he's got limbs, a body, he walks and talks, has a social security number, and he typically wears clothes in public. He holds a steady job. He's a citizen of country X.

Now look over there. It's Mike. Mike was in the war. Mike is in a wheelchair these days. He has a head, a body, but is missing some limbs. Everybody agrees Mike's a good guy. Mike is a good person.

Here's someone really interesting. A modern marvel of medicine. It's Jim. Jim has a head, he has limbs, and a body, but several years ago his heart failed him. His heart just stopped working. But he was lucky. He underwent a successful heart transplant surgery. Jim doesn't have his own heart anymore. Jim has Jake's heart. Jake was a good person too.  Jake was a good person, but Jake was a little odd. Jake, you might say, was nuts. Jake even believed that he was Jesus Christ, sometimes. Jake had a good heart, though. And now Jim has Jake's heart. But even though Jim has Jake's heart, Jim doesn't think he's Jesus Christ. Jim is just like Jim always was, except his ticker is in tip-top shape.

Jack is a bit of a sad case. Let me tell you his story. Jack was driving out by Corcoran State Prison one night and got in a bad accident. His body and limbs were unscathed in the crash, but his brain was all smashed up. Jack was in dire need of a new brain, he needed a brain transplant. Remarkably, doctors in the emergency room were able to find a fresh brain for Jack. But as a result of an extraordinary series of mix-ups, caused by inept record-keeping and carelessness on the part of medical staff, Jack didn't get the brain he was supposed to get (the brain of a 65 year old female, named Gwen) -- oh no. Jack didn't get that brain, Jack got Charles Manson's brain.

When "Jack" was released from the hospital, "Jack" felt a little sluggish, as one might expect after a brain transplant, but he could walk and talk and eat and drink and generally felt pretty good. Jack didn't feel himself, though. And Jack wasn't acting like himself, either. To the people who knew and loved Jack, Jack wasn't Jack anymore. For instance, when Jack's wife of 30 years, Nancy, welcomed him home for the first time after the brain operation, Jack stared at her with the eyes of a maniac and remarked to her: "I'm nobody. I'm a tramp, a bum, a hobo. I'm a boxcar and a jug of wine. And a straight razor ... if you get too close to me." Needless to say, this frightened Nancy.

By the time the error was detected at the hospital, Jack had already gone on a crime spree involving a series of unspeakably gruesome acts of depravity. What had gotten in to Jack? Everybody wondered whether it was the brain transplant that had caused this terrifying change in his behavior. Eventually, the police caught up with Jack and he was taken in on numerous charges including murder and kidnapping.

Meanwhile, the neurosurgeon that had performed the brain transplant convinced the authorities to let him perform another operation on Jack, to take out Manson's brain and replace it with the healthy female brain. Jack returned to the hospital and left several weeks later, in evident good health and spirits, equipped with a 65-year old female's brain, and expressing a newfound appreciation of Oprah Winfrey, knitting, and flower pattern dresses. Unfortunately, a judge's order sent Jack back to jail to await trial.

Jack was unhappy in jail and was growing depressed in dark solitary cell. He thought often of his husband, Martin, and how much he would love to return to his garden or just sit in the rocking chair and knit a sweater on a lazy Sunday. The public defender assigned to the case assured Jack that he had a plan. He told Jack:

-- "I know how to win this case. You didn't commit those crimes. It wasn't you. It was Charlie's brain".

-- "But they have witnesses.", said Jack. "I don't remember any of it. They say it was me, though. They all saw me. Blood was on my hands. They have my DNA. Everything points to me. I guess I did it. I'm doomed."

-- "Jack, that wasn't you!"

-- "My name isn't Jack, It's Gwendolyn. Call me Gwen, please!"

Jack sat silently in the courtroom as the trial went on, day after day, another witness describing in gory detail his horrific and senseless acts. Jack often welled up with tears as he listened to this disturbing litany, not remembering any of it, but increasingly resigned to the overwhelming probability of his guilt.

But Jack's lawyer had something extraordinary in store for everyone, an unprecedented legal gambit that he was sure would turn the tide. He called Jack to the stand. Jack testified that he didn't remember any of the crimes, that he had had never seen any of the victims whose pictures, one after the other, were presented to him.

-- "Ladies and gentleman of the jury. There is a reason that Jack doesn't remember any of this, that Jack doesn't recognize any of these faces. It's because Jack didn't commit these crimes. Jack's no murderer. It wasn't Jack, at all ...", pausing for effect: "Ladies and gentleman it was Charles Manson's brain!!!! The person who should be on trial, is resting quietly, awash in formaldehyde, in a 6-litre mason jar."

Everyone in the courtroom gasped. The prosecution objected vigorously: "There is no evidence whatsoever of Manson's brain's involvement, nothing. This is a last ditch effort to derail these grave proceedings by turning this trial into a bizarre farce!" The worldwide news media began covering the trial, referring to the bizarre ordeal as, simply, Mansonstein.

But Jack's lawyer was not done.

-- "Your Honor, I now call to the stand my final witness: Charles Manson's brain!"

-- "Objection!! Your Honor, the witness has not been announced, this is highly irregular -- brains do not commit crimes, people do! "

-- "Objection overruled, I will allow the witness. I am curious to see what Charles Manson's brain has to say."

At that point, Jack's neurosurgeon entered the courtroom carrying a semi-transparent glass jar with a human brain submerged in a yellow-tinged liquid. The surgeon carefully approached the stand, deposited the jar on the seat of the witness chair, and hooked up electrodes that were attached to the surface of the brain to an large electronic device that was itself attached to a pair of speakers."

Jack's lawyer began his questioning. "Mr. Manson, er ... Mr. Manson's brain, where were you the night of the 23rd of August?"

Manson's brain (heard through speakers): "You can't prove anything. There's nothing to prove. Every man judges himself. He knows what he is. You know what you are, as I know what I am, we all know what we are. That cat, Jack, knows what he knows, he's a real deal killing machine, I been locked up in this septic tank, my brain on ice."

Public Defender: "Have you ever seen the inside of Jack's skull?"

Manson's Brain: "Sure I been in there. Had a real good time, caught up with some old friends and played nasty tricks on people. Jack's skull treated me real nice! We had a good ole party and then we parted ways."

Public Defender: "So you committed the gruesome acts of violence attributed to Jack's person?"

Manson's Brain: "Yeah, I did done that, those things. Laddaddada!! I'm your Huckleberry, now get me out of this god-forsaken brain tank and let my spirit free again!!"

The courtroom is stunned. There is a hushed silence and then murmuring and then a isolated shouts and then a gathering chorus: "Free Jack! Free Jack! Jack is innocent, Jack is innocent!"

And the curtains close.

Tuesday, March 19, 2013

Reaction Time Experiments: Functional Neuroimaging on the Cheap

I my last post I discussed Max Coltheart's claim that functional neuroimaging has nothing to say when it comes to deciding between two psychological theories. I concluded that, really, you just have to concede the point -- but on very narrow grounds. Yes, if two theories do not make a prediction about a functional neuroimaging measure, then it is of course trivially true that fMRI cannot adjudicate between them. This is nothing specific to brain imaging. One can say, generally, that for any dependent measure to be useful in deciding between two scientific hypotheses, the hypotheses must make predictions about outcomes on that variable. I further concluded that there is no special reason why psychological theories cannot make predictions about functional neuroimaging data. Here I want to elaborate on that point, because, clearly, at least a few people believe that there is a reason to exclude functional neuroimaging data from having a say in psychological theory-testing.

In a recent talk at the Rotman Research Institute in Toronto, Russ Poldrack made the not wholly tongue-in-cheek remark that when it comes to testing psychological theories, you can think of functional neuroimaging as "like a really expensive reaction time experiment". This formulation works for me. And you know what? I like it even better when you flip it around, like this: A reaction time (RT) experiment is like a really cheap functional neuroimaging study. 

Hear me out. The logic of an RT experiment is simple. When a subject responds more slowly in one condition than another, we say that this condition required more "cognitive processing". More cognitive processing is more work. Who carries out that work? I think B.F. Skinner might even admit (if pressed) that it's the brain that carries out that work. Thus, RT is a measure of brain work -- RT is a measure of brain activity. It is no coincidence that the dominant analytic paradigm in functional neuroimaging over past 30 years -- "subtraction logic" -- was pilfered outright from the Donders/Sternberg approach to psychological experiments using RT.

It must be said on behalf of RT: pretty darn good temporal resolution, terrible spatial resolution. Indeed, with RT, you only get one voxel. (Even EEG guys scoff at the spatial resolution of RT-imaging experiments). Well, no, it's not a fancy technique. No glossy brochures, no booth at SFN, no sales divisionIt doesn't involve measuring brain waves, magnetic fields, electron spins, or anything like that. Nevertheless, make no mistake, RT is a neuroscience technique. And although RT experiments aren't really ever presented in the form of "images", they perfectly well could be. After all, EEG was around awhile before its untidy squiggles were repackaged as pretty color interpolated brain maps. Want to get your RT-Imaging experiment published in Neuroimage? How about something like this: statistical parametric mapping on RT data (SPM-RT). Homage to the square.

   Figure 1. SPM-RT Image, Lexical Decision: Frequency Contrast (High > Low) p < .01, uncorrected.

So if you present your RT "contrasts" (your t-tests, your ANOVAs, your regressions) in Josef Albers hues, then, yes, you're doing a very cost-effective version of brain imaging. (This is good news if you're a cognitive psychologist angling for that "cognitive neuroscience" faculty job: tout all your good work in one-voxel statistical parametric mapping of RT data; talk up your expertise in "RT-imaging"). In fact, you can probably even jerry-rig SPM to analyze your RT data and display it in that iron-hot color scale in the SPM glass brain. (Don't forget to turn off temporal smoothing and convolution with the HRF.) You too, devotee of RT methodology, can take advantage of the seductive allure of brain imaging.

But, but, but, but .... wait a second, you say! "RT is a behavioral measure, and fMRI is a brain measure. They're different!" This is something like a category error, I say. RT is a measure of elapsed time. It has zero scientific significance in and of itself. Its significance rests entirely in the interpretation given to it, the inferences made with it. And those inferences, as I have already mentioned, are about "mental effort", "cognitive processing", which are mere synonyms for "brain work", "brain activity". As a matter of fact, fMRI is only a little bit "closer to the metal" -- the measure is blood oxygenation and the inference is about neural activity in this or that region.

Adrien Owen and colleagues have shown that patients in a vegetative state who otherwise have no way of communicating with the outside world, can nevertheless participate in simple psychological experiments while undergoing fMRI scanning. To answer "yes", the patient imagines that he or she is playing tennis, and a particular network of brain areas lights up. Thus, the patient communicates his or her intentions by "thinking" in a certain way. Is this a behavior? I don't see why not. It just so happens that this behavior is witnessed by an expensive MRI scanner, rather than a cheap "button box". The point being that the distinction between brain and behavior isn't so cut-and-dried.

Lets return to the original question. Can functional neuroimaging data constrain psychological theory? Well, it remains the case that if a theory doesn't make a prediction about a particular outcome measure, then it's hard to see how that measure is going to be of much help testing your theory. But if you accept my argument that RT, the workhorse dependent variable of experimental psychology for the last 50 years, is itself a brain measure, then we see that the whole argument is something of a mirage, a false dichotomy, a hot-iron herring. On the bright side, does this mean we can finally merge cognitive neuroscience and cognitive psychology? Can we have a new field, a new annual meeting? I propose Cognitive Neuropsychognomics. Organizers, founders, wherever you are, I have only one request: hold the annual meeting mid-February in Kauai or somewhere else suitably tropical.

Tuesday, July 17, 2012

A trick question: What has functional neuroimaging told us about the mind?

I'm not actually going to try and answer the question posed in the title, which is taken from Coltheart's (2006) legendary critique of functional neuroimaging in a special issue of the journal Cortex. To summarize, Coltheart concluded that, no, functional neuroimaging hadn't told us anything about the mind so far; and he challenged others to prove him wrong. Others have taken the bait and made heroic and important efforts to meet Coltheart's challenge. Rather, I'm simply going to question the question. Because it's a tricky question. Indeed, it's a trick question.

This may seem obvious and elementary, but to answer Coltheart's question one first has to know what his question means. And the critical word in his question that we need to define is "mind". What has functional neuroimaging told us, he asks, about the mind.  As good reductionists, we might say: "wait, the mind is the brain, they denote the same object". The morning star is the evening star. The two are synonymous. So, substituting, "brain" for "mind", we rephrase the question as follows: "What has functional neuroimaging told us about the brain".  And then the answer is trivial, because novel information about the brain gotten from functional neuroimaging answers the challenge. Case closed.

If only it were so easy. In fact, when Coltheart uses the word "mind" he's not talking about the "brain". He's talking about something else. Is the mind a thing? Or is it an idea? Can we touch it? Can we define it?  Although Coltheart uses the word "mind" 11 times in his essay, he never actually provides a definition. I'm not going to try and define it, either.

If we look elsewhere in the paper for clues about what is meant by "the mind", however, we find that Coltheart is really concerned with psychological theories and the ability to adjudicate between them. But what are psychological theories about? 

From the first paragraph of the Introduction (emphasis added):

There are numerous different reasons for doing [functional neuroimaging]. I will consider only one of these reasons, namely, to try to learn more about cognition itself.

And then:

Although there exists a huge volume of recent literature reporting the results of cognitive neuroimaging studies, there are surprisingly few papers which have evaluated this technique as a way of studying cognition itself.

OK. We can infer that psychological theories are about cognition itself. And we can further infer that "cognition itself" is separate and conceptually distinct from the "brain". And so what is the "mind"? It's cognition itself. It's not the brain. It's apart from the brain -- it's itself.

Another hint comes further down on page 1 (emphasis in original):

My paper, like Henson’s, is concerned solely with the impact of functional neuroimaging on the evaluation of theories that are expressed solely at the psychological level.

So the mind is akin to cognition itself, and cognition itself is described solely at the psychological level. In other words, don't mix up the brain with cognition itself. Stay at the psychological level. Any reference to the brain in a pure psychological theory is verboten. That would be mixing levels. Mixing metaphors with molecules.

The question, then, is whether functional neuroimaging can adjudicate between competing psychological theories that are about cognition itself. And what sort of predictions do these (pure) psychological theories actually make? They make predictions about behavior. Coltheart uses as an example two theories of reading that posit serial or parallel processing, respectively. For instance, in serial processing:

When a word contains an irregular grapheme-phoneme correspondence, the later in that word that correspondence is the less the word’s reading-aloud latency will be affected by its irregularity.

Here, the dependent variable is a measure of response time, or latency, and whether it depends on spelling irregularity.  In all of Coltheart's examples of the predictions made by psychological theories the dependent variable is always a behavioral measure (i.e. reaction time, accuracy, etc.) and never a brain measure.

But that follows perfectly from Coltheart's stipulations. Theories are expressed at the psychological level. They don't make reference to the brain. And because they don't make reference to the brain, they don't make predictions about the brain.  And because they don't make predictions about the brain, ipso facto, functional neuroimaging cannot adjudicate between said theories.

Coltheart was right!

But Coltheart's conclusion is not an empirical one, based on an evaluation of the functional neuroimaging literature. It is simply axiomatic. He defines a psychological theory as that which does not refer to the brain ("expressed solely at the psychological level") and which makes predictions about variables (reaction time, accuracy) that cannot be measured by functional brain imaging. So we know, a priori, that functional neuroimaging cannot tell us anything about these particular psychological theories. And all the articles in the special issue of Cortex that attempted to meet Coltheart's challenge were doomed to failure, a priori, on the basis of a simple logical deduction.

Coltheart was right, but it was a trick question.

Suppose that we loosen up Coltheart's definition of psychological theories to allow for those that make contact with the brain? And if such theories make predictions about states of affairs in the brain, then, guess what, all of sudden functional neuroimaging can adjudicate between two competing psychological theories that make different predictions about brain activation.

And is there any reason a psychological theory, other than for reasons of ideological purity, should not make contact with brain? Or is that some sort of contradiction? Can psychology be mixed with neuroscience? Isn't that what's called ..... cognitive neuroscience?

My answer is, of course, that "psychological theories" can certainly make reference to the brain. Indeed, such theories can be fundamentally neuroscientific. They may borrow concepts and terminology from multiple traditions of inquiry, including cognitive psychology, neurology, neuroscience, psychiatry, neuroanatomy, genetics, physiology, sociology, economics, and so on.  Buchsbaum & D'Esposito (2008) made a similar point in a book chapter a few years ago and I'll quote it before a brief conclusion:

A hypothetical philosopher of metaphysics might ask the question: ‘What has physics told us about metaphysics?’ to which he might answer that because metaphysics is the science of the non-physical, physics by definition has nothing to say about metaphysics. Unlike metaphysics and physics, however, most would agree that the study of the mind and the study of the brain are fundamentally related if not, indeed, one and the same endeavour. There is therefore absolutely no reason why psychological theories should not refer to and make explicit predictions about brain function, nor is there any reason to think such theories would, upon making contact with neuroscience, somehow cease to be ‘psychological’. 

To conclude, in 2006 Coltheart asked whether functional neuroimaging had told us anything about the mind. He concluded "no". There have been many earnest  and technically innovative efforts over the years to persuade he and other skeptics otherwise. Cognitive ontologies, Bayesian probabilistic reverse inference, forward inference, reverse inference, structure-function association, etc. etc. etc. All of this stuff is fantastic and welcome and is enormously useful to cognitive neuroscience. But none of it answers Coltheart's challenge, in the way it was framed. Because it's impossible. The game was rigged.

So here's my answer: we simply must concede the point. No, functional neuroimaging does not and cannot adjudicate between theories expressed solely at the psychological level that make no predictions about the brain. How could it? It was a trick question all along.

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.

Wednesday, September 1, 2010

More work needed

Over at Talking Brains there is an ongoing debate about whether language researchers in cognitive neuroscience are making enough progress. Fedorenko and Kanwisher think that "more work is needed", and that the answer is functional localizers. And they want to help. It's all very magnanimous.

Surely, though, there was never a greater scientific truism than the statement "more work is needed"! According to Karl Popper, more work is always needed, forever, in perpetuity. The scientific process is an inherently Sisyphean enterprise. We're doomed to be forever wrong, with probability = 1.

But of course Fedorenko and Kanwisher are right: more work is needed in the cognitive neuroscience of language. Nevertheless, I welcome you to read their remarks, because it seemed to me that there was also the implication that in two particular areas of study, namely theory-of-mind and the ventral visual stream, there is perhaps a somewhat less urgent need for more work:

"Several regions in the ventral visual stream have been shown to be exquisitely specialized for processing visual stimuli of a particular class (see e.g., Kanwisher, 2010, PNAS, for a recent overview). Furthermore, Saxe and colleagues have shown that a region in the right temporo-parietal junction selectively responds to stimuli that require us to think about what another person is thinking (e.g., Saxe & Powell, 2006, Psych Sci, and many other papers; see the publications section on the SaxeLab’s website: "

Surely if there were anything that was almost as good as scientifically true, verified, incontrovertible, consensus-worthy, etc. -- it would be that the fusiform face area (FFA in the fusiform gyrus) and the theory-of-mind area (TPJ in the right temporo-parietal junction) are 100% functionally specialized. Here, try this out. Next time you're at a neuroscience conference, out to dinner with a diverse assortment of your cleverest colleagues, stand up and say loudly and earnestly that you know with as much certainty as you know anything in this world that the right TPJ functions to "let one know what others are thinking" and that it only functions to "let one know what others are thinking". Add that it has been "demonstrated beyond any doubt". Then finish off the thought by saying: "No more work needed. It's a wrap". I promise that everyone will nod in vigorous -- in violent and perhaps even hysterical -- agreement.

OK, one caveat. Make sure Professor Jason Mitchell is not in attendance. Because he authored a paper in 2008 published in Cerebral Cortex entitled:

Activity in the right temporo-parietal junction is not selective for theory-of-mind

He also wrote this (2009, Philos Trans Royal Society):

"Intriguingly, the same pattern of medial frontal, temporo-parietal and medial parietal activity consistently accompanies a number of disparate tasks that, at first blush, appear to share little in common with mentalizing. Most notably, these regions are engaged by attempts to prospectively imagine the future or to retrospectively remember the past (Addis et al. 2007; Buckner & Carroll 2007; Schacter et al. 2007; Spreng et al. in press). For example, Addis et al. asked participants alternately to imagine their future self experiencing a specific event (cued by an object, such as ‘dress’) or to recall an actual event that occurred in their past. Both prospection and episodic memory engaged a highly overlapping network of regions that included MPFC, bilateral TPJ and medial parietal cortex. In addition, the same network has also been argued to play a role in spatial navigation (Buckner & Carroll 2007; Spreng et al. in press)."

Could it be that the TPJ does a whole bunch of things, indeed -- that the TPJ is a veritable Johannes Factotum, a cognitive dilettante flitting about from task to task, engaged in all manner of cognitive processes, and lending its functional activation about with a cavalier and unsophisticated disregard for the tenets of domain specificity? It seems that there is considerable evidence that this may be the case.

More from Professor Mitchell, same 2009 review:

"The fact that prospection, episodic memory, spatial navigation and mentalizing each draws on the same set of brain regions suggests that each likewise draws on a common set of cognitive processes. What cognitive challenge might these four disparate tasks share? One answer to this question is that each requires perceivers to conjure up a world other than the one that they currently inhabit: prospection obliges perceivers to imagine possible future scenarios; episodic memory relies on the reconstruction of bygone events; and spatial navigation often includes simulations of possible routes between locations. In other words, prospection and episodic memory can be conceived of as forms of mental time travel, and spatial navigation as a form of mental teleportation, all of which depend critically on the ability to project oneself outside of the here and now, imagining times or locations other than the one currently being experienced (Suddendorf & Corballis 2007)."

OK, I should also warn that you might also want to make sure that Drs Grit Hein and Robert Knight are not in attendance when you announce that the TPJ is the theory-of-mind region and that the TPJ is only the theory-of-mind region. Because they wrote a paper entitled: "Superior Temporal Sulcus, It's my area or is it?" in the Journal of Cognitive Neuroscience (2008). Here's an interesting quote:

"Activity in the 'ToM regions' in posterior STS, intersecting the parietal lobe, also correlated with differential effects in attentional reorienting. In line with our findings, this argues against distinct functional subregions in the STS and adjacent cortices and is more in favor of the assumption that the same STS region can serve different cognitive functions, as a flexible component in networks with other brain regions. There is abundant evidence for this proposition from neuroanatomical studies revealing bidirectional connections of the STS region with a variety of brain structures, such as the ventral and medial frontal cortex, lateral prefrontal and premotor areas, the parietal cortex, and mesial temporal regions (Seltzer & Pandya, 1989a, 1994)."

In line with the network assumption, four of the five
studies in the ‘‘ ToM’’ category (Kobayashi et al., 2007; Voellm et al., 2006; Takahashi et al., 2004; Gallagher et al., 2000) report medial prefrontal activity together with STS activation, whereas STS activity in speech pro cessing was more accompanied by inferior frontal activation (Uppenkamp, Johnsrude, Norris, Marslen-Wilson, & Patterson, 2006; Rimol, Specht, Weis, Savoy, & Hugdahl, 2005). This might imply that the STS serves ToM when coactivated with medial prefrontal regions, while being
involved in speech processing when coactivated with the inferior frontal cortex."

Let me conclude by saying I'm a huge fan of cognitive neuroscience researchers advancing strong theories about the function(s) of a brain area. I have written previously that that the way forward is to embed our function terms in our structural ones -- to link them up. I have written with Mark D'Esposito a most thorough and plaintive hymn on the (quixotic?) quest for structure-function unity in phonological working memory ("The Search for the Phonological Store: From Loop to Convolution").

The "Fusiform Face Area" is a wonderful example of the merging of structure and function terms -- they are joined in a single moniker: FFA. Could the proposed link be wrong? Indeed it could. The function word "face" is just renting the space between "fusiform" and "area", it can always be cleaved, excised, extracted from that position if the evidence warrants. Until that time, however, more work is needed.