Brain Scanning - Just the Tip of the Iceberg?

Neuroimaging studies may be giving us a misleading picture of the brain, according to two big papers just out.

By big, I don't just mean important. Both studies made use of a much larger set of data than is usual in neuroimaging studies. Thyreau et al scanned 1,326 people. For comparison, a lot of fMRI studies have more like n=13. Gonzalez-Castillo et al, on the other hand, only had 3 people - but each one was scanned while performing the same task 500 times over.

Both studies found that pretty much the whole brain "lit up" when people are doing simple tasks. In one case it was seeing videos of people's faces, in the other it was deciding whether stimuli on the screen were letters or numbers.

With all that data, the authors could detect effects too small to be noticed in most fMRI experiments, and it turned out that pretty much everywhere was activated. The signal was stronger in some areas than others, but it wasn't limited to particular "blobs".

So conventional fMRI experiments may just be showing us the tip of the iceberg of brain activity. In a small study, only the strongest activations pass the statistical threshold to show up as blobs, but that doesn't mean the rest of the brain is inactive. It just means it's less active. The idea that only small parts of the brain are 'involved' in any particular task may be a statistical artefact.

In fact, I wonder if the whole idea of treating statistically significant blobs as different from nearly-significant areas is itself a form of the error of interacting effects?

As if that wasn't enough, Gonzalez-Castillo further show that there are lots of activations in the brain - even to very simple stimuli - that might go undetected in conventional studies, because they don't follow the time-course predicted by the usual models.

Have a look -

This shows the average neural activation from various regions of the brain during a letter-number task. The two areas I've highlighted in red are the primary visual cortex, and they do follow the expected 'boxcar' pattern - the brain is active when the stimuli are on the screen, inactive when they're not. But you can see that all kinds of other brain areas are also responding to the stimuli - just in different ways.

For example, the left primary motor cortex was activated during the task. That area controls the right hand, and that makes sense, as people responded by pressing buttons with the right hand. But interestingly, the same area on the other side of the brain was deactivated at exactly the same time, even though people weren't doing anything with their left hand.

These papers illustrate the fact that conventional fMRI is a blunt instrument that often only tells us about the most straightforward events that happen in the brain. A bit like how we only hear the shouts and screams from through our neighbor's walls, not their normal conversations, which aren't loud enough to reach our ears.

That's the bad news, but every blob has a silver lining. fMRI is clearly more powerful than most neuroscientists have realized, and this holds out hope for cracking some of the trickiest questions. As Gonzalez-Castillo et al put it

This result helps narrow the gap between thousands of fMRI manuscripts showing limited activation in response to tasks and cognition theories that defend that cognition—understood as the process of “configuring the way in which sensory information becomes linked to adaptive responses and meaningful experiences”—can only result from the distributed collaboration of primary sensory, upstream and downstream unimodal, heteromodal, paralimbic, and limbic regions... [we were able to] switch from a regime where activity detection relates primary to sensory processing to a more sensitive regime, where activity detection includes also cognitive processes with subtler BOLD signatures.

Link: See also the interesting discussion here: Surely, God loves the .06 (blob) nearly as much as the .05.


Thyreau, B., Schwartz, Y., Thirion, B., Frouin, V., Loth, E., Vollstädt-Klein, S., Paus, T., Artiges, E., Conrod, P., Schumann, G., Whelan, R., and Poline, J. (2012). Very large fMRI study using the IMAGEN database: Sensitivity–specificity and population effect modeling in relation to the underlying anatomy NeuroImage DOI: 10.1016/j.neuroimage.2012.02.083

Gonzalez-Castillo, J., Saad, Z., Handwerker, D., Inati, S., Brenowitz, N., and Bandettini, P. (2012). Whole-brain, time-locked activation with simple tasks revealed using massive averaging and model-free analysis Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1121049109

Mystery Joker Parodies Neuroscience

Someone has created a hilarious spoof paper poking fun at neuropsychoanalysis (but all of fMRI takes some hits too): A Triple Dissociation of Neural Systems Supporting ID, EGO, and SUPEREGO.

Featuring gems such as

• Authors "Steven Z. Fisher and Stephen T. Student" with contact details "mother@amaliastate.edu".
• "Twenty-four healthy participants (all 19-year-old white, male undergraduates who sat near each other in an Introductory Psychology course and were raised in upper middle class suburban New
  England neighborhoods) were scanned but 17 were excluded for not following instructions or falling asleep in the scanner."
• "If you’re like us, you’ve probably been thinking that Social Neuroscience, Neuroeconomics, and Developmental Social Cognitive Affective Clinical Neuroscience are just not cutting edge enough
  anymore. Do not despair. This study represents the first of what is likely to be a productive and active new field of Psychoanalytic Neuroscience."

It really is very funny, but it's also deadly accurate in its highlighting serious problems that plague a certain genre of neuroimaging papers. Who made it? The PDF appeared on Dropbox a couple of weeks ago and, while a few people have Tweeted about it, no-one has claimed ownership, yet.

For the record, it wasn't me.

Voodoo Neuroscience Revisited

Two years ago, neuroscientists were shaken by the appearance of a draft paper showing that half of the published work in a particular field had fallen prey to a major statistical error.

Originally called "Voodoo Correlations in Social Neuroscience", it ended up with the less snappy name of Puzzlingly high correlations in fMRI studies of emotion, personality, and social cognition. I prefer the old title.

The error in question is now known variously as the "circular analysis problem", "non-independence problem" or "double-dipping" although I still call it the "voodoo problem". In a nutshell it arises whenever you take a large set of data, search for data points which are statistically significantly different from some baseline (null hypothesis), and then go on to perform further statistics only on those significant data points.

The problem is that when you picked out the statistically significant observations, you selected the data points that were especially "good", so if you then do some more analyses only on those data, you are almost guaranteed to find something "good". To avoid this you need to make sure that your second analysis is truly independent of your first one.

Anyway, Vul and Pashler, the main authors of the original voodoo article, have just written a short piece in NeuroImage offering some reflections on the paper and the aftermath. They don't make any major new arguments but it's a good read. Particularly fun is their explanation of what inspired them to look into the voodoo problem:

In early 2005 a speaker in our department reported that BOLD activity in a small region of the brain can account for the great majority of the variance in speed with which subjects walk out of the experiment several hours later (this finding was never published as far as we know). The implications of this result struck us as puzzling, to say the least: Are walking speeds really so reliable that most of their variability can be predicted? Does a focal cortical region determine walking speeds? Are walking speeds largely predetermined hours in advance? These implications all struck us as far-fetched...

But they reveal that it was one paper in particular that set them off voodoo-hunting

Our interest in probing the matter was further whetted by an episode occurring a short while later: Grill-Spector et al. (2006) reported that individual voxels in face selective regions have a variety of stable stimulus preferences; in a critical commentary, Baker et al. (2007) found that the analysis used to ascertain this fact implicitly built these conclusions into the method, such that the same analysis applied to noise data (voxels from the nasal cavity) revealed a similar variety of stable preferences. It occurred to us that a similar circularity might underlie the puzzlingly high correlations.

To their credit, Grill-Spector et al quickly accepted Baker et al's criticism and admitted that some of their original conclusions had been wrong.

Vul, E., and Pashler, H. (2012). Voodoo and circularity errors NeuroImage DOI: 10.1016/j.neuroimage.2012.01.027

Neuroskeptic In The Papers

Two more academic papers have appeared that refer to this blog:

The Openness of Illusions is a philosophy piece about the epistemological implications of optical illusions. It cites my post about a paper dealing with the spooky Hollow Face Illusion. Long-time readers will remember this, but most of you probably won't, so here it is again; it truly is weird:

In my view, an even better demonstration of the same effect is the incredible magic dragon:

You can make your own dragon by printing it out from this helpful page. It takes like 5 minutes to make and it'll provide hours of philosophical fun.

Meanwhile, Stereotypes and stereotyping: What's the brain got to do with it? takes a neuro-skeptical look at the psychology and neuroscience of prejudice. It flatters me with a mention:

It should go without saying that activity in the brain does not indicate in any way whether a mental act is hard-wired (Beck, 2010). It is equally absurd to argue that the amygdala is on anyone’s team or feels occasionally upset. Alas, non-experts should not be expected to spot such fundamental flaws in reasoning without help.

Thus scientists using neuroscientific methods to study phenomena of social relevance are not only expected to be particularly critical towards over-interpreting their own findings, but also to monitor the ways in which their and other researchers’ data are reported in the media. Courageous attempts to counter overblown neuroscience-based claims in non-scientific outlets have so far resulted in numerous critical blogs (e.g., http://www.talkingbrains.org; http://neuroskeptic.blogspot.com) as well as in the publication of counterstatements in popular magazines (e.g., Aron et al., 2007).

How Realistic is fMRI?

How representative are fMRI experiments? Is "the brain" that we investigate with fMRI the same brain that we use outside the MRI scanner?

A new paper from Bernhard Hommel and colleagues of Leiden in the Netherlands offers some important caveats. They looked to see what effect playing some recorded MRI scanner sounds had on people's ability to perform some simple cognitive tasks, while sitting outside the scanner.

MRI is notoriously noisy. When you have an MRI scan you have to wear earplugs to protect against the sound but they only block out some of it. Opinions differ on whether the sound is pleasant or not. Personally I find the repetitive tick-tock rather soothing now, but then I've heard it many times over the years. First-timers can find it quite overwhelming.

Anyway, Hommel et al found that while scanner noise had no overall effects on reaction time or accuracy, it actually improved performance on three measures of "cognitive control".

For instance in a task in which participants had to respond to the colour of a circle by pressing the left or the right arrow key, they were slower to react when the circle appeared on the "wrong" side of the screen, i.e. on the left when the correct answer was the right arrow. This slowing of responses caused by a stimulus-response clash is called the Simon effect.

The results showed that the Simon effect was reduced by noise. The same thing happened in two other studies: noise meant better performance.

All of the noise effects were modest and the sample sizes were also quite small (14-18 per task, with everyone studied twice, noisy vs silent) but this paper joins a number of others raising questions about the representativeness of fMRI, with evidence that fMRI activates the brain and maybe even improves mood (although I doubt that last one).

The authors' interpretation is that the noise made people pay more attention to the tasks, to compensate for the distraction, and that this means that fMRI studies may be biased in their measurements of cognitive control:

Generalizing from fMRI findings to behavioral observations and vice versa seems to be more problematic than commonly thought, at least as far as control  processes are concerned. In a sense, then, investigating cognitive processes by means of  fMRI... is inevitably facing Heisenberg’s (1927) uncertainty principle, according to which the act of measurement can change what is being measured.

To my mind the biggest weakness of this is that it only looked at noise. While scanners are noisy, that's not the only distracting thing about them: during an fMRI study you also have to lie down, in a small confined tube, and your only way to see the "screen" on which experimental stimuli are shown is indirectly via a small mirror which often doesn't give a good view.

So ironically, I'm not sure how realistic this study is...


Hommel, B., Fischer, R., Colzato, L., van den Wildenberg, W. and Cellini, C. (2011). The effect of fMRI (noise) on cognitive control. Journal of Experimental Psychology: Human Perception and Performance DOI: 10.1037/a0026353

Was Evita Lobotomized?

Eva Peron, or Evita, is perhaps the most famous woman in Latin American history. As the wife of Argentinian leader Juan Peron she was immensely popular. But she died at the age of just 33 from cervical cancer, after a two year struggle with the disease.

A new paper makes the startling claim that Eva Peron may have received a prefrontal lobotomy in the months before her death. The lobotomy is best known as a treatment for mental disorders such as schizophrenia, but according to Nijensohn et al, Peron was given the operation as a kind of pain relief.

The claim was first made in 2005 by Dr George Udvarhelyi, who worked as a neurosurgeon in Argentina before moving to John Hopkins in Baltimore. After his retirement, Udvarhelyi told the Baltimore Sun that he'd performed the operation.

The authors of this paper checked out the claims against his unpublished memoirs. It turns out that they've just written Udvarhelyi's biography, and managed to slip in a plug for their book. Indeed, this paper could be seen as a plug. But anyway.

The early 1950s were the golden age of lobotomy and it does seem plausible that if she had one, it would have been kept secret. But it seems that the only direct evidence is Udvarhelyi's testimony. The authors point to various facts that could be seen as consistent with it, like this memoir by a close friend:

“The illness continued to advance. I visited her one afternoon andwas shown a notebook belonging to her brother Juancito. There was a drawing of Evita with her head criss-crossed by scissors. The sinister image suggested that she was either crazy or brain damaged. I found her very thin, quiet, and deeply introverted”

But to be honest this is pretty weak. The authors also admit that in interviews with scholarly experts on Peron's illness, they were all surprised by the idea.

They then point to postmortem X-rays of Peron's skull which were made public in 1955 to prove that her corpse hadn't been burned (long story). These, they suggest, show evidence of the kind of burr holes that were used to insert the lobotomy tools -

And they say that a photo of her shortly before her death shows an "indentation at the coronal level" -

Hmm. Not sure what to make of those. Ultimately though, the authors admit that the only way to know for sure would be to exhume Evita and study her skull, but this is unlikely to happen any time soon.

Nijensohn DE, Savastano LE, Kaplan AD, & Laws ER Jr (2011). New Evidence of Prefrontal Lobotomy in the Last Months of the Illness of Eva Perón. World neurosurgery PMID: 22079825

Susan Greenfield's Dopamine Disaster

It's Susan Greenfield again.

Continuing her campaign warning of the dangers of modern technology in terms of their effects on the vulnerable brains of the young, the British neuroscientist and Baroness has written another article. This is the latest of many. None of them have been in peer reviewed academic journals.

This one's behind the Great Times Paywall so I can't link to it, but it's called Are video games taking away our identities?

The first part of the article is hard to argue against. Either you'll agree with it or you won't. Personally, videogames as Greenfield describes them bear little resemblance to any games that I've played recently. Similarly for her account of the Internet. But maybe this rings true for some:

Screen images do not depend for their impact on seeing one thing in terms of anything else. Their premium lies invariably in their raw sensory content... we are perhaps heading towards a much weaker sense of identity by engaging in a world where we are the passive recipient of senses and where there is no fixed narrative of past and future but an atomised thrill of the moment. One could even suggest that the constant self-centred readout on Twitter belies a more childlike insecurity, an existential crisis.

Greenfield then moves into discussing the brain, and this is where the science comes in. This is her "home turf" - she's Professor of physiology at Oxford. Yet it's a shambles.

There is one alarm bell ringing, which suggests that increasing 2D screen existence may be having undesirable effects: it is the threefold increase over the past decade in prescriptions for drugs for attention deficit hyperactivity disorder.

While this could be due to changes in doctors’ prescribing procedures, or indeed to a greater recognition and medicalisation of attentional problems, a third possibility could indeed be that if the young brain is exposed from the outset to a world of fast action-reaction, of instant new screen images flashing up with each press of a key, then such rapid interchange might lead to a shorter attention span.

The human condition can be basically divided into two alternating modes, first described by Euripedes... the rational “bread force”, characterised by a strong cognitive take on the world — a personalised past, present and future, in turn related to an active prefrontal cortex and lower levels of the brain chemical dopamine; and the “wine force”, more the state of young children or those adults indulging in “letting themselves go”, in situations perhaps involving wine, women and song, where a strong sensory environment demands less reflection, more passive reaction.

...An increase in physiological arousal can be linked to excessive release of dopamine. Could the screen experience be tilting this ancient balance in favour of the more infantile, senses-driven brain state?

Greenfield says that high dopamine and low prefrontal cortex activity is associated with irrationality and a deficit in attention. Video games are causing a flood of dopamine and causing ADHD. That would make sense, if ADHD was caused by too much dopamine, and if drugs for ADHD reduced dopamine release.

The problem is that it's the exact opposite. Drugs for ADHD increase dopamine release and ADHD is widely believed (although it's controversial) to be caused by a dopamine deficit.

Greenfield then says "We know too that dopamine suppresses the activity of neurons in the prefrontal cortex", but this is a serious oversimplification. Dopamine has complex effects on target neurons. It can inhibit firing, but it can also excite it. It all depends on the conditions. Here's what the authors of an influential scientific review said in 2004: "It is agreed by most researchers is that dopamine is a neuromodulator and is clearly not an excitatory or inhibitory neurotransmitter"

Some say that dopamine helps to "tune" the prefrontal by increasing the signal to noise ratio - more signal, less noise. Here's one of the most cited papers about dopamine and the PFC: Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey.

Remember that drugs for ADHD like Ritalin, which are sometimes used illicitly by students without that disorder to help them focus and concentrate, cause dopamine release. If Greenfield were right, it would be the exact opposite.

...[other] people characterised by an underactive prefrontal cortex are those with schizophrenia, this time not due to physical damage but rather a chemical imbalance, in particular an excessive amount of the transmitter dopamine. In schizophrenia, like children, the patient is easily distracted, cannot interpret proverbs, is not strong on metaphor but takes the world literally; it is a vibrant world that can implode on, and overwhelm, the fragile firewall of the schizophrenic mindset.

This again is a serious simplification. Actually, you don't need to be a neuroscientist to work that out. Just recall the earlier bit: Greenfield has said that ADHD is caused by too much dopamine leading to an underactive prefrontal cortex. Now she says that schizophrenia is the same. So why are the symptoms of ADHD completely different from schizophrenia?

Why is it, in fact, that Ritalin and similar dopamine releasing drugs help with ADHD, but can make schizophrenia worse?

As a neuroscientist, I can tell you that we don't really know what's going on with dopamine in ADHD or schizophrenia. There's decent evidence that dopamine is involved in schizophrenia, but not in any straightforward sense. Schizophrenia is now believed to be linked to reduced dopamine in the prefrontal cortex, and too much in other areas.

As for ADHD, remember: the leading theory is that it's about too little dopamine. Not too much.

The only disease that we know certainly is associated with too little dopamine is Parkinson's. Contrary to Greenfield's theory, people with Parkinson's often have cognitive and mood problems as well as the better known difficulties with movements. They're not super intelligent, prefrontal-cortex-wielding geniuses.

I appreciate that an opinion piece in the Times is never going to be a rigorously argued scientific paper, but the fact that Greenfield's article contains several claims which are the exact opposite of the truth (or at least of current scientific thinking) calls her credibility into serious question.

You Use Your Partner To Phone And Play Angry Birds. Literally.

WITH lots of weddings expected on Tuesday, people in love across the world are getting ready for their latest fix.

But should we really characterize the intense devotion shown by people in love, as love? A recent experiment that I carried out using neuroimaging technology suggests that love-related terms like “romance” and “soulmates” aren’t scientifically accurate - not compared to a word we use to describe our relationships with our smartphones. That word is “owning an iPhone.”

As a branding consultant, why am I even writing this article for the NYT? Never mind. Earlier this year, I carried out an fMRI experiment to find out whether iPhones were really, truly addictive, no less so than alcohol, cocaine, shopping or video games (sic)... wait, are those last two actually addictive? Whatever, let's just say they are.

In conjunction with the San Diego-based firm MindSign Neuromarketing (kerching! Wait, did I write that, or just think it?), I enlisted eight men and eight women between the ages of 18 and 25. Our 16 subjects were exposed separately to audio and to video of a wife or husband.

In each instance, the results showed activation in both the audio and visual cortices of the subjects’ brains. In other words, when they were exposed to the video, our subjects’ brains didn’t just see their partner, they “heard” them, too. This powerful cross-sensory phenomenon is known as "the brain storing information about people and objects, and retrieving it in response to related stimuli", or "memory" to use the technical term.

But most striking of all was the flurry of activation in the insular cortex of the brain, which has also been associated with seeing an iPhone. The subjects’ brains responded to the sound of their partner as they would respond to the presence or proximity of a top of the range smartphone (with free WiFi in thousands of locations!)

In short, the subjects didn’t demonstrate the classic brain-based signs of addiction when they were shown pictures of their lovers. Instead, they made calls and played Angry Birds on them.

---

The silliness of equating insula activation on fMRI with love and using this to argue that we love our iPhones as a recent crap OpEd in the New York Times did, has been excellently covered over at [Citation Needed], Neurocritic and many others. I'm sure you've heard plenty about this story already.

But let's set aside the fact that loads of other things, by no means limited to disgust and drug addiction, are known to involve the insula in fMRI. Let's assume (as the NYT piece did) that the only two things that had ever been shown to activate the insula were seeing an iPhone and seeing someone you love.

This study still wouldn't show that people love their phones. You could equally well turn the whole thing on its head and argue that it shows that we think of people we love as something to make phone calls with. Hey, the brain activity is the same as when you look at an iPhone.

This might strike you as implausible, but given the fMRI data alone, you have no grounds for saying one interpretation is more or less plausible than the other.

There are countless other interpretations, each equally plausible given the imaging data. Maybe the insula is only about love, and the activation to the iPhone is due to conditioned association (you call people you love on it). Maybe it's about objects you see every day, which includes your phone and people you love. Maybe...

The only reason to prefer any particular interpretation would be because you have evidence from outside neuroimaging - from other areas of neuroscience or psychology. So if you discovered that insula lesions cause people to be unable to fall in love (they don't, as far as I know) then you could make a case for the love interpretation. But only then.

Neuroimaging, on its own, can't tell us anything about the brain. It's like a peek under the hood of your car. If you already know how a car works, you can look under the hood and work out what's going on, and what's gone wrong. But only if you have that prior knowledge. Otherwise, it's just a big set of metal pipes.

Neuroscience Fails Stats 101?

According to a new paper, a full half of neuroscience papers that try to do a (very simple) statistical comparison are getting it wrong: Erroneous analyses of interactions in neuroscience: a problem of significance.

Here's the problem. Suppose you want to know whether a certain 'treatment' has an affect on a certain variable. The treatment could be a drug, an environmental change, a genetic variant, whatever. The target population could be animals, humans, brain cells, or anything else.

So you give the treatment to some targets and give a control treatment to others. You measure the outcome variable. You use a t-test of significance to see whether the effect is large enough that it wouldn't have happened by chance. You find that it was significant.

That's fine. Then you try a different treatment, and it doesn't cause a significant effect against the control. Does that mean the first treatment was more powerful than the second?

No. It just doesn't. The only way to find that out would be to compare the two treatments directly - and that would be very easy to do, because you have all the data to hand. If you just compare the two treatments to control you might end up with this scenario:

Both treatments are very similar but one (B) is slightly better so it's significantly different from control, while A isn't. But they're basically the same. It's probably just fluke that B did slightly better than A. If you compared A and B directly you'd find they were not significantly different.

An analogy: Passing a significance test is like winning a prize. You can only do it if you're much better than the average. But that doesn't mean you're much better than everyone who didn't win the prize, because some of them will have almost been good enough.

Usain Bolt is the fastest man in the world (when he's not false-starting himself out of races). Much faster than me. But he's not much faster than the second fastest man in the world.




Nieuwenhuis S, Forstmann BU, & Wagenmakers EJ (2011). Erroneous analyses of interactions in neuroscience: a problem of significance. Nature neuroscience, 14 (9), 1105-7 PMID: 21878926