Monday, December 27, 2010

Why are the letters "z" and "x" so popular in drug names?



Freelance medical and science writer Rob Stepney noticed the rapid growth of "x" and "z"-named products included in the British National Formulary (BNF). So for the Christmas 2010 issue of BMJ (Stepney, 2010), he investigated this phenomenon:
Of 1436 products added to the BNF between 1986 and 2005, more than a fifth had names that began with z or x or contained a prominent x or z within them. In 1986, only 19 branded drugs began with one of these letters. Over the next two decades, the number of brands beginning with a z increased by more than 400% (to 63) and those beginning with an x increased by 130% (to 16). In the same period, the overall content of the BNF grew by only 80%.
Why did it happen? He first asks whether use of the voiced fricative “zuh” sound might be special in some way, but he quickly dismisses this possibility, along with the popularity of z in the Middle East.

Instead, he speculates that x and z might have been perceived as making products stand out in a crowd:
Reflecting their infrequent occurrence in English words, x and z count for 8 and 10 points in Scrabble, the highest values (along with j and q) in the game. So names that contain them are likely to seem special and be memorable. “If you meet them in running text, they stand out,” is the way one industry insider explained. Generally, they are also easy to pronounce.
In my view, however, the rush to uniqueness resulted in an overcrowded field. The market became saturated with X and Z brand names, which can cause confusion.


Fig 1 (Stepney, 2010). Number of drugs with a brand name beginning with z or x listed in March edition of BNF for each year. New formulations of existing brands and zinc related compounds have been excluded.

For instance, the August 9, 2007 newsletter from the Institute for Safe Medication Practices discusses Progress with preventing name confusion errors and links to a document on the most problematic look-alike and sound-alike drug names of 2006-2007 (PDF). These include:
ZYPREXA (olanzapine) and ZYRTEC (cetirizine)

Name similarity has resulted in frequent mixups between Zyrtec, an antihistamine, and Zyprexa, an antipsychotic. Patients who receive Zyprexa in error have reported dizziness, sometimes leading to a related injury from a fall. Patients on Zyprexa for a mental illness have relapsed when given Zyrtec in error.
Other frequently confused Z/X pairs:
Zantac – Xanax
Zantac – Zyrtec
Zestril – Zyprexa
Zestril – Zetia
Zocor – Zyrtec
At any rate, here's Stepney's (2010) conclusion:
I suggest that this phenomenon arose because of the fast rate at which new products were being introduced, the fact that the difference between many “me too” drugs was more apparent than real, the immense rewards that were seen to accrue from innovative marketing, and the fact that the ploys available for use in the naming of drugs are so restricted.
A full list of the drugs mentioned in the article can be viewed here.

Reference

Stepney, R. (2010). A dose by any other name would not sell as sweet. BMJ, 341:c6895 DOI: 10.1136/bmj.c6895

Sunday, December 26, 2010

2009 Lie of the Year Redux: Palin's so-called Death Panels



In 2009, a straw man was introduced into the U.S. health care debate. Death panels invoked the specter of rationing medical procedures provided for the sick and the elderly. In the name of cost cutting, blared the phony rhetoric on talk radio and Sarah Palin's Facebook page, the Obama administration would sanction euthanasia for elders and the terminally ill under provisions of the health care bill. This would save on expensive treatments that prolong patients' lives but increase the deficit, claimed the conservative crew. However, these scare tactics were an outright lie.

A year ago, Palin's "death panel" charge was named Lie of the Year, as covered here by the Wall Street Journal:
Former Alaska GOP Gov. Sarah Palin’s Facebook allegation that the Democrats’ health-care overhaul would include “death panels” to decide whether seniors and disabled people were worthy of care was named “Lie of the Year” by fact-checkers at Politifact.com.
PolitiFact.com is the 2009 Pulitzer Prize-winning, non-partisan project of the St. Petersberg Times newspaper. Its Truth-O-MeterTM carefully evaluates the statements of political figures, pundits, and organizations and finds them to be TRUE, MOSTLY TRUE, HALF TRUE, BARELY TRUE, FALSE, or PANTS ON FIRE [as defined here].

They don't exactly give Barack Obama a free pass:


PANTS ON FIRE = The statement is not accurate and makes a ridiculous claim.

So the crowning of Palin's so-called death panels as lie of the year was not a politically motivated act.
PolitiFact's Lie of the Year: 'Death panels'

By Angie Drobnic Holan
Published on Friday, December 18th, 2009 at 5:15 p.m.


Of all the falsehoods and distortions in the political discourse this year, one stood out from the rest.

"Death panels."

The claim set political debate afire when it was made in August, raising issues from the role of government in health care to the bounds of acceptable political discussion. In a nod to the way technology has transformed politics, the statement wasn't made in an interview or a television ad. Sarah Palin posted it on her Facebook page.

Her assertion — that the government would set up boards to determine whether seniors and the disabled were worthy of care — spread through newscasts, talk shows, blogs and town hall meetings. Opponents of health care legislation said it revealed the real goals of the Democratic proposals. Advocates for health reform said it showed the depths to which their opponents would sink. Still others scratched their heads and said, "Death panels? Really?"

The editors of PolitiFact.com, the fact-checking Web site of the St. Petersburg Times, have chosen it as our inaugural "Lie of the Year."

Why is this story relevant again now?? It's because of a new article in the New York Times:
Obama Returns to End-of-Life Plan That Caused Stir

By ROBERT PEAR
Published: December 25, 2010


WASHINGTON — When a proposal to encourage end-of-life planning touched off a political storm over “death panels,” Democrats dropped it from legislation to overhaul the health care system. But the Obama administration will achieve the same goal by regulation, starting Jan. 1.

Under the new policy, outlined in a Medicare regulation, the government will pay doctors who advise patients on options for end-of-life care, which may include advance directives to forgo aggressive life-sustaining treatment.
One of the issues that has most riled the conservative commentariat is the secrecy advocated by some Democrats, such as Oregon Representative Earl Blumenauer:
After learning of the administration’s decision, Mr. Blumenauer’s office celebrated “a quiet victory,” but urged supporters not to crow about it.

“While we are very happy with the result, we won’t be shouting it from the rooftops because we aren’t out of the woods yet,” Mr. Blumenauer’s office said in an e-mail in early November to people working with him on the issue. “This regulation could be modified or reversed, especially if Republican leaders try to use this small provision to perpetuate the ‘death panel’ myth.”
I don't agree with this strategy at all. It's bound to backfire, and it already has. Instead, the logical way to counteract the ‘death panel’ myth is with evidence to the contrary. But this doesn't work with those who are already convinced otherwise (e.g, the tea party, Palin fans, etc.). Because of pre-existing cognitive biases, no amount of scientific evidence, or quotation of the actual provisions of the legislation/regulation, will change their minds.

So why bother, you say? What's the point? As a scientist, I'm not going to sit idly by while a vast swath of the American populace tries to influence personal health care decisions with their ignorance. The NYT cited a peer-reviewed study that supports the benefits of end-of-life planning: The impact of advance care planning on end of life care in elderly patients: randomised controlled trial (Detering et al., 2010; PDF). They also linked to a letter to the editor of the Journal of the American Geriatrics Society that reviewed the literature on advanced directives (Fischer et al., 2010; PDF) and concluded that ADVANCE DIRECTIVE DISCUSSIONS DO NOT LEAD TO DEATH.

Yet, the conservative pundits are trying to convince everyone that the opposite is true, without presenting a shred of evidence. Previously, I wrote about how a study in the New England Journal of Medicine (Temel et al., 2010) showed that the Limbaugh/Palin "death panels" extend the lives of terminally ill patients. This paper demonstrated that the introduction of palliative care shortly after the diagnosis of metastatic lung cancer not only improved the patients' quality of life, but also extended median survival from 8.9 months to 11.6 months:
The NEJM study enrolled 151 patients with newly diagnosed metastatic non–small-cell lung cancer. Seventy-four received standard care and 77 patients received palliative care, which included meetings with a member of the palliative care team (board-certified palliative care physicians and advanced-practice nurses). The first meeting was within 3 weeks of enrollment, and subsequent meetings were held on a monthly basis, with additional sessions at the discretion of the patient and the clinical treatment team. Patients assigned to standard care did not meet with the palliative care team (unless requested). All patients continued to receive standard oncology care for the duration of the study.

These meetings are the so-called "death panels" that would have been covered by Medicare...
Don't believe the rhetoric. The true death panels are those who want to deny health care to low-income Americans. Do they plan to pay all medical care for the uninsured out of their own pockets? If not, then who will, besides the government? Oops, looks like the anti-Obamacare crowd has just condemned them to die.

Tuesday, December 21, 2010

Neuroradiology as Art

Crucifixion, by Francis Bacon (1933).
Crucifixion (1933) (oil on canvas) was subsequently purchased by Sir Michael Sadler (who, other than friends or relations, was the first to buy a painting), and who also commissioned a second version, Crucifixion (1933) (chalk, gouache and pencil), and sent Bacon an x-ray photograph of his own skull, with a request that he paint a portrait from it. Bacon duly incorporated the x-ray directly into The Crucifixion (1933).
A paper by an interdisciplinary team of Serbian radiologists, anatomists, artists, and pathologists examined how neuroradiological images have been used as a form of artistic expression (Marinković et al., 2010). They started by describing skull x-rays incorporated into the paintings of Francis Bacon and Diego Rivera, then gave examples of contemporary artists who transform computerized tomography (CT) and magnetic resonance images (MRI) into art. These works include Wooden Brain (The 3D MRI Cubes) by Neil Fraser and "Art and Science #1" by Marjorie Taylor, which can be seen at the The Museum of Scientifically Accurate Fabric Brain Art.

I would add to the list any number of works by Damien Hirst, including this self-portrait:


...which he incorporated into this album cover for See the Light by The Hours.



Marinković and colleagues (2010) mentioned the commercialization of neuroradiology and colorized pictures of the brain by companies such as shutterstock, where you can subscribe for $249 a month and download stock photos of a "female doctor examining a brain cat scan" and "colorful brain model isolated on dark background" (much like this one).

The authors also surveyed 12,673 artworks in books and Google images. They found that neuroradiological images were used in 29 works (1.01%) created by 31 artists (1.58% of 1,964 total).

They wished to make their own contributions to this collection, and they did so with three pieces presented in the paper. In one of these, they
...performed an x-ray of four post mortem hemispheres following the injuction of a radiopaque substance into their sulci and insertion of the copper wires around the corpus callosum and along the calcarine and parieto-occipital sulci. The radiograph of one of the hemispheres was then superimposed in Phototshop with the photograph of the subsequently made cast of the cerebral arteries.

Radiological Image, by Marinković et al. (2010).

Finally, they...
...made an inverse image of a colorized brain in a front view. this image was then superimposed with a photograph of illuminated optic fibers in the background.

Cognitive Radiation, by Marinković et al. (2010).


Anatomy and art intersect in a number of places, at the Mütter Museum in Philadelphia, the Morbid Anatomy website, the Bioephemera website by Jessica Parker, and Gunther von Hagens' BODY WORLDS (the Bioethics of which is discussed here), among many others.

Portraits of the Mind: Visualizing the Brain from Antiquity to the 21st Century by Carl E. Schoonover is a popular new book that's currently out of stock at Amazon.

Neuroradiology, and especially the development of beautiful colorized diffusion tensor images, has captured the minds of artists, designers, and the public.

From the Human Connectome Project, an effort to map the white matter connectivity of the human brain.

Reference

Marinkovic, S., Stošic-Opincal, T., Štrbac, M., Tomic, I., Tomic, O., & Djordjevic, D. (2010). Neuroradiology and Art: A Review and Personal Contribution The Tohoku Journal of Experimental Medicine, 222 (4), 297-302. DOI: 10.1620/tjem.222.297

"I think one of the things is that, if you are going to be a painter, you have got to decide that you are not going to be afraid of making a fool of yourself.

I think another thing is to be able to find subjects which really absorb you to try and do.

I feel that with out a subject you automatically go back into decoration because you haven't got the subject which is always eating into you to bring it back - and the greatest art always returns you to the vulnerability of the human situation".

-Francis Bacon

Tuesday, December 14, 2010

“Bob the Builder” Goggles in Ophthalmology



Case Report: novel treatment initiated by the patient to treat her symptoms of ocular neuromyotonia, or spontaneous spasms of the extraocular muscles.

As part of the Christmas 2010 issue of BMJ, Weston et al. (2010) reported the case of a 68 yr old woman with intermittent diplopia, or double vision. A cataract on her left eye was removed, which improved her vision.
Unfortunately her symptoms continued. Her diplopia was elicited during orthoptic review, showing a left exotropia [a form of strabismus where the eyes are deviated outward], with updrift, measuring 40 prism dioptres. There was limitation of adduction and depression of the left eye. Imaging showed no structural lesion. The episodes increased in frequency to 50-100 times per day. However, she found one day, while playing with her grandson, that wearing a pair of his tight “Bob the Builder” goggles prevented the episodes from occurring (Figure 1, above).
For those who don't know, Bob the Builder is a character on a children's show in the UK. He works as a building contractor.


The patient's newly found treatment was a success, and she sported Bob the Builder goggles on a regular basis:
As a result she took to wearing the goggles daily around the house, particularly to watch the television. She also tried other types of goggles, including swimming goggles, but these were not as effective. She was diagnosed with idiopathic ocular neuromyotonia affecting left lateral rectus and left superior rectus muscles. Symptom control was achieved with carbamazepine after a trial of gabapentin failed.

In the same Christmas Cheer issue of BMJ is this callipygian coverage of a "newly discovered" reflexology of the buttocks (McLachlan, 2010). The author submitted a phony query letter to “The Jerusalem Conference on Integrative Medicine.”
I write to ask if you would be interested in a presentation on my recent work on integrative medicine. I am an embryologist by background, with an extensive publication record, in journals including Nature and the Proceedings of the Royal Society, and have written an award winning text book on medical embryology. Recently, as a result of my developmental studies on human embryos, I have discovered a new version of reflexology, which identifies a homunculus represented in the human body, over the area of the buttocks. The homunculus is inverted, such that the head is represented in the inferior position, the left buttock corresponds to the right hand side of the body, and the lateral aspect is represented medially. As with reflexology, the “map” responds to needling, as in acupuncture, and to gentle suction, such as cupping. In my studies, responses are stronger and of more therapeutic value than those of auricular or conventional reflexology. In some cases, the map can be used for diagnostic purposes.



This was a complete hoax, of course, but it's worth reading the rest of the article and some of the ensuing media/blog coverage (e.g., Be Honest. Does this Study Make My Butt Look Big? and Pulling reflexology out of one's nether regions).

References

McLachlan JC (2010). Integrative medicine and the point of credulity. BMJ 341:c6979.

Weston, K., Bush, K., Afshar, F., & Rowley, S. (2010). Can he fix it? Yes, he can! BMJ, 341 (dec08 3) DOI: 10.1136/bmj.c6645

Saturday, December 11, 2010

Perspectives on Psychological Science: Blogs Don't Exist

The Seductive Allure of Neuroscience Explanations


The previous post, Voodoo Correlations: Two Years Later, was a retrospective on the neuroimaging methods paper that was widely discussed in the blogosphere before it was considered "officially" published (Vul et al., 2009). The article, a controversial critique of the statistical analyses used by fMRI investigators in social neuroscience, made its initial appearance on Ed Vul's website once it was accepted by Perspectives in Psychological Sciences. This caused considerable consternation among the criticized authors and the journal editor (Ed Diener).

Now, as part of the November 2010 issue of the journal (Diener's last as editor), six invited articles on Neuroimaging: Voodoo, New Phrenology, or Scientific Breakthrough? appear in a Special Section on fMRI (Diener, 2010). I was pleased to see that one of the articles addressed The Appeal of the Brain in the Popular Press (Beck, 2010), since this has been a major theme of my blog for almost five years. However, I was disappointed that the word "blog" was not mentioned at all in Beck's article.

This should have come as no surprise, given the journal's response to bloggers in May 2009. The Editor's Introduction is worth a mention for the issues it raises about peer review and publication in these modern times.
PREPUBLICATION DISSEMINATION

As soon as I accepted the Vul et al. article, I heard from researchers about it. People around the globe saw the article on the Internet, and replies soon appeared as well. Although my plan was to publish the article with commentary, the appearance of the article on the Internet meant that researchers read the article without the accompanying commentaries and replies that I had planned to publish with it.

In some fields such as economics, it is standard practice to widely disseminate articles before they are published, whereas in much of psychology this has been discouraged. An argument in favor of dissemination is that it speeds scientific communication in a fast-paced world where journal publication is often woefully slow. An argument against dissemination of articles before publication is that readers do not have the opportunity to simultaneously see commentary and replies. ... In the Internet age, the issue of prepublication distribution becomes all the more important because an article can reach thousands of readers in a few hours. Given the ability of the Internet to communicate so broadly and quickly, we need greater discussion of this issue.
In reply, I wrote:
Bloggers have discussed this specific issue months ago. For example, as noted in Mind Hacks,
The paper was accepted by a peer-reviewed journal before it was released to the public. The idea that something actually has to appear in print before anyone is allowed to discuss it seems to be a little outdated (in fact, was this ever the case?).
And The Neurocritic opined that...
[The aggrieved authors] are not keeping up with the way that scientific discourse is evolving. Citing "in press" articles in the normal academic channels is a frequent event; why should bloggers, some of whom are read more widely than the authors' original papers, refrain from such a practice? Is it the "read more widely" part?

-from The paper formerly known as "Voodoo Correlations in Social Neuroscience", by The Neurocritic

Diener originally solicited six commentaries on the Vul et al. paper for the May 2009 issue of the journal. Ironically, authors on two of the papers have serious blogs:

Statistical Modeling, Causal Inference, and Social Science is a blog written by Andrew Gelman, a Professor of Statistics and Political Science at Columbia. He was one of the first to blog about the paper in Suspiciously high correlations in brain imaging studies, with a more detailed post a month later (More on the so-called voodoo correlations in neuroscience). Lindquist and Gelman (2009) applauded the discussion engendered by "pre-publication dissemination":
Their article has in a short time given rise to a spirited debate about key statistical issues at the heart of most functional neuroimaging studies. The debate provides a useful opportunity to discuss core statistical issues in neuroimaging and ultimately provides a chance for the field to grow and move forward.

[citation needed] is the blog kept by Tal Yarkoni, a Post-Doc at the University of Colorado Boulder. He happens to be an expert in statistics for fMRI analysis, and another one of the authors invited to submit a paper for the Vul, Harris, Winkielman, and Pashler festschrift/verdammung (Yarkoni, 2009):
In this article, I argue that Vul et al.'s primary conclusion is correct, but for different reasons than they suggest. I demonstrate that the primary cause of grossly inflated correlations in whole-brain fMRI analyses is not nonindependence, but the pernicious combination of small sample sizes and stringent alpha-correction levels. Far from defusing Vul et al.'s conclusions, the simulations presented suggest that the level of inflation may be even worse than Vul et al.'s empirical analysis would suggest.
His blog started in October 2009, after the commentaries were published.


The Appeal of the Brain in the Popular Press

That brings us back to the article by Diane Beck, an Assistant Professor in Psychology and Cognitive Neuroscience at the University of Illinois Urbana-Champaign. She examines the distorted media coverage of neuroimaging studies, and possible reasons for it (Beck, 2010):
Since the advent of human neuroimaging, and of ... fMRI in particular, the popular press has shown an increasing interest in brain-related findings. In this article, I explore possible reasons behind this interest, including recent data suggesting that people find brain images and neuroscience language more convincing than results that make no reference to the brain (McCabe & Castel, 2008; Weisberg, Keil, Goodstein, Rawson, & Gray, 2008). I suggest that part of the allure of these data are the deceptively simply messages they afford, as well as general, but sometimes misguided, confidence in biological data. In addition to cataloging some misunderstandings by the press and public, I highlight the responsibilities of the research scientist in carefully conveying their work to the general public.
While reading through the examples of poor media coverage, imagine the shock of recognition if you were to realize that you have written several trenchant blog posts criticizing these very articles. Yet all this work (and the writings of many others) is rendered invisible to the mainstream of the Association for Psychological Science.

Why is blogging so non-existent in these circles? There's a large thriving community of science blogs. Go to ResearchBlogging.org and look under Psychology, for starters. An excellent example of a psychology blog written by a senior investigator is BishopBlog by Professor Dorothy Bishop, who studies children's communication impairments at Oxford. Two of my favorite posts are The difference between p < .05 and a screening test and Science journal editors: a taxonomy.

As for Beck's hit list and The Seductive Allure of Neuroscience Explanations (Weisberg et al., 2008), we have:

(1) Men see bikini-clad women as objects, psychologists say
In other words, the choice of tasks or conditions that the researcher will contrast is absolutely critical to obtaining activity, as well as any inference that can be made about this activity. By omitting this fact from a press article, one gets the impression that participants are asked to do a single task in the scanner, such as view pictures of women in bikinis, and voilà, a set of areas light up (Landau, 2009)...
Here's Spanner or Sex Object? by The Neurocritic:
OK, the abstract doesn't specifically mention the tool/bikini experiment, so we have to rely on newspaper articles and quotes from the first author. Judging from the first 4 paragraphs of the Guardian article, Fiske's conclusions rely on the logical fallacy of reverse inference - one cannot directly infer the participants' cognitive or emotional state from the observed pattern of brain activity in neuroimaging experiments. How do we know that the "sex object" neural response was related to tool use? Did the experiment require the subjects to use tools? Did it explicitly ask them to anticipate using tools? How about watching others use tools?

(2) Greene JD, Sommerville RB, Nystrom LE, Darley JM, Cohen JD. (2001). An fMRI investigation of emotional engagement in moral judgment. Science 293:2105-8.
What does it mean to say that moral decisions are associated with activity in regions implicated in emotional processing (Greene et al. 2001)? What exactly is meant by moral decisions or emotional processing? The only way to really understand these statements is to also know what are not moral decisions, and how emotional processing is being defined.
Here's Everybody's a Neurocritic!
In that paper, the authors
reported that the medial frontal gyrus and other brain regions linked to emotion become more active when people contemplate "personal" moral dilemmas--such as shoving the man onto the trolley tracks or removing a man's organs against his will to save five transplant recipients--compared with when they weigh impersonal moral dilemmas--such as flipping a switch to save the workers or declaring bogus business expenses on a tax return.
Besides the medial frontal gyrus [BA 9/10, which did not replicate in Experiement 2], what were these other brain regions linked to emotion? Did they include the insula? No, they did not. They included the posterior cingulate gyrus (which has some grounding in reality) and the L and R angular gyri (which does not).

(3) A Neuroscientific Look at Speaking in Tongues

...In the press article, the author describes a study that used single photon emission computed tomography to compare regional cerebral blood flow in women speaking in tongues to cerebral blood flow in the same women singing gospel music (Newberg, Wintering, Morgan, & Waldman, 2006). Although glossolalia and singing both involve verbal utterances and evoke religious meaning in practioners, the women described a lack of voluntary control over their vocalizations only during glossolalia. The study found decreased activity in the prefrontal cortex during glossolalia, a result that the study’s authors describe as consistent with the women’s descriptions of a lack of intentional control over their utterances. The press article does not explicitly endorse this conclusion but instead chooses to quote Andrew Newberg, the lead author on the study: “The amazing thing was how the images supported people’s interpretation of what was happening. The way they describe it, and what they believe, is that God is talking through them” (Carey, 2006). ... The study’s result, however, is neither amazing nor does it support any particular cause of glossolalia. Decreased activity in the prefrontal cortex could be due to any number of reasons...
Glossolalia from The Neurocritic still gets comments from those who feel they speak in tongues, probably because it appears on the first page of a Google search on the topic.

And The New York Times Is Speaking In Tongues:
As I mentioned, oh, just the other day, (1) the authors did not correct for multiple comparisons, (2) the spatial resolution of SPECT is not that great, and (3) the rCBF reductions in right dorsolateral prefrontal cortex and (especially) the left caudate were their most significant findings.

(4) Different brain responses found in homosexual, heterosexual men [original link from the article was broken]
...the Associated Press (Schmid, 2005) reported on a PET study showing that when homosexual men sniffed a derivative of testosterone, their hypothalamus responded more like that of heterosexual women than heterosexual men (Savic, Berglund, & Lindstrom, 2005). The Associated Press rightly stated that “the findings clearly show a biological involvement in sexual orientation.” However, they then make an erroneous jump from describing homosexuality as being biological to being innate, primarily in the form of a quote from Dr. Sandra Witelson: “It is one more piece of evidence … that is showing that sexual orientation is not all learned” (Schmid, 2005). A difference in the brain in no way indicates that the behavior under study is not learned...
See Sweat, Urine, and Sexual Orientation and The PNAS Word from 2006. [I got tired of waiting for the embargo to lift, so these aren't as critical as I might have liked.]

You get the idea. But in the end, it's all for naught because Diener (2009) has spoken:
I believe that the debate can itself stimulate useful discussions about scientific practices and communication. Further discussion of the issues should now take place in journals that are focused on imaging and neuroscience, so that the readers there can judge and benefit from the ensuing discussions.

References

Beck, D. (2010). The Appeal of the Brain in the Popular Press. Perspectives on Psychological Science, 5 (6), 762-766 DOI: 10.1177/1745691610388779

Diener E (2009). Editor's Introduction to Vul et al. (2009) and Comments. Perspectives on Psychological Science 4:272-273,

Diener E (2010). Neuroimaging: Voodoo, New Phrenology, or Scientific Breakthrough? Introduction to Special Section on fMRI. Perspectives on Psychological Science 5:714-715.

Lindquist MA, Gelman A (2009). Correlations and Multiple Comparisons in Functional Imaging: A Statistical Perspective (Commentary on Vul et al., 2009). Perspectives on Psychological Science 4:310-313.

Vul E, Harris C, Winkielman P, Pashler H (2009). Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition. Perspectives on Psychological Science 4:274-290.

Weisberg DS, Keil FC, Goodstein J, Rawson E, Gray JR. (2008). The seductive allure of neuroscience explanations. J Cogn Neurosci. 20:470-7.

Yarkoni T. (2009). Big Correlations in Little Studies: Inflated fMRI Correlations Reflect Low Statistical Power—Commentary on Vul et al. Perspectives on Psychological Science 4:294-298.


The Seductive Allure of Neuroscience Blogs

Wednesday, December 8, 2010

Voodoo Correlations: Two Years Later



The end of 2008 brought us the tabloid headline, Scan Scandal Hits Social Neuroscience. As initially reported by Mind Hacks, a new "bombshell of a paper" (Vul et al., 2009) questioned the implausibly high correlations observed in some fMRI studies in Social Neuroscience. A new look at the analytic methods revealed that over half of the sampled papers used faulty techniques to obtain their results.

-from Voodoo Correlations in Social Neuroscience, by The Neurocritic

The paper by Vul, Harris, Winkielman, and Pashler made its initial appearance on Ed Vul's website once it was accepted for publication by Perspectives in Psychological Sciences. Originally titled "Voodoo Correlations in Social Neuroscience", it was eventually renamed the more globally palatable "Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition" at the request of the editor (after much consternation from the criticized authors). This paper sparked intense debate in the field of functional neuroimaging, much of which occurred in the blogosphere (at least initially).1




Are blogs good or bad for the enterprise of scientific peer review? At present, the system relies on anonymous referees to provide "unbiased" opinions of a paper's (or grant's) merits. For today, the discussion will focus on peer review of papers in scientific journals.

-from The Voodoo of Peer Review, by The Neurocritic
Many of the aggrieved researchers in the neuroimaging community were appalled that bloggers were discussing Vul's accepted paper before it was "properly" published (and before they had time to comment themselves). But two research groups quickly issued replies:
Two rebuttals were released online shortly thereafter: one by Jabbi et al. (PDF) and an invited reply by Lieberman et al. (PDF).

What's the problem here? It's that bloggers were writing about it! That authors and anonymous commenters somehow sullied their ideological purity by entering the free-wheeling, fast-moving world of the blogosphere. But in the modern era, why wait 5 months for a paper to be "officially" published before you're allowed to discuss it? And despite what the critics of Voodoo say, Vul et al.'s paper was not plastered all over the popular press (unlike many of the Voodoo findings themselves)...

The only other mainstream media exposure has been from Sharon Begley of Newsweek, who covered the issue in her blog (i.e., The 'Voodoo' Science of Brain Imaging and More on Brain Voodoo) and in one of her magazine columns. But many are dubious. According to Seed [That Voodoo That Scientists Do]:

Two groups of neuroimaging scientists, shocked by the speed with which this paper was being publicly disseminated, wrote rebuttals and posted them in the comments section of several blogs, including Begley's. Vul followed up in kind, linking to a rebuttal of the rebuttals in the comment sections of several blogs. This kind of scientific discourse — which typically takes place in the front matter of scholarly journals or over the course of several conferences — developed at a breakneck pace, months before the findings were officially published, and among the usual chaos of blog comments: inane banter, tangents, and valid opinions from the greater public.
The usual chaos of blog comments? Hello?? How about anonymous referees for journals? Are they never ever guilty of reviews filled with inane banter and tangents? We've all had exposure -- whether from our bosses, advisors, or colleagues or through our own experience -- to rude and nasty and ill-informed reviewers. And many journal editors do not rein them in. The Neurocritic has been a proponent of completely open peer review, where the identity of the authors and the reviewers is known (see Anonymous Peer Review Means Never Having to Say You're Sorry, Peer Review Trial and Debate at Nature, and Double-Blind Bind). That way, Dr. Nasty can't hide behind the shield of anonymity when making those dumb-ass comments.

-from The Voodoo of Peer Review, by The Neurocritic

This issue is relevant again today because of the fallout over the infamous arsenic paper (Wolfe-Simon et al., 2010), which claimed it had isolated a bacterium that can substitute arsenic for phosphorus. Publication of the paper was preceded by a Sphinxlike press release: "NASA will hold a news conference at 2 p.m. EST on Thursday, Dec. 2, to discuss an astrobiology finding that will impact the search for evidence of extraterrestrial life." After the paper appeared online in Science, negative reactions from qualified and prominent scientists were swift. One of the most visible (and withering) critiques was written by Dr. Rosie Redfield, a microbiologist at the University of British Columbia:

Arsenic-associated bacteria (NASA's claims)

Here's a detailed review of the new paper from NASA claiming to have isolated a bacterium that substitutes arsenic for phosphorus on its macromolecules and metabolites. ... Basically, it doesn't present ANY convincing evidence that arsenic has been incorporated into DNA (or any other biological molecule).

. . .

Bottom line: Lots of flim-flam, but very little reliable information. The mass spec measurements may be very well done (I lack expertise here), but their value is severely compromised by the poor quality of the inputs. If this data was presented by a PhD student at their committee meeting, I'd send them back to the bench to do more cleanup and controls.
CBC News covered the critical backlash and NASA's reply, which was anti-blog:

NASA's arsenic microbe science slammed

. . .

Debate shouldn't be in media: NASA

When NASA spokesman Dwayne Brown was asked about public criticisms of the paper in the blogosphere, he noted that the article was peer-reviewed and published in one of the most prestigious scientific journals. He added that Wolfe-Simon will not be responding to individual criticisms, as the agency doesn't feel it is appropriate to debate the science using the media and bloggers. Instead, it believes that should be done in scientific publications.

Redfield said the reason she posted the review on her blog is partly because scientific publications such as Science — and the debates therein — are typically behind a paywall and inaccessible to the public.

"I blog openly…to bring this stuff more into the open where everybody can see it," she said.

Redfield has now posted a draft of her official letter to Science.

For full coverage of the matter, I recommend Is That Arsenic-Loving Bug — Formerly an Alien — a Dog? and The Wrong Stuff: NASA Dismisses Arsenic Critique Because Critical Priest Not Standing on Altar by David Dobbs, "This Paper Should Not Have Been Published" by Carl Zimmer, and An arsenic bacteria postmortem: NASA responds, tries to pit blogs vs. “credible media organizations” by Ivan Oransky (for starters).


Returning now to Voodoo Correlations... In the November 2010 issue of Perspectives in Psychological Sciences (online December 7, 2010), outgoing editor Ed Diener has assembled an fMRI Special Section looking back at those heady days and forward into the future:


Neuroimaging: Voodoo, New Phrenology, or Scientific Breakthrough? Introduction to Special Section on fMRI

Ed Diener

In response to the widespread interest following the publication of Vul et al (2009), Perspectives Editor Ed Diener invited researchers to contribute articles for a special section on fMRI, discussing the promises and issues facing neuroimaging.


Mistreating Psychology in the Decades of the Brain

Gregory A. Miller

Scientists tend to consider psychology-biology relationships in two distinct ways: by assuming that psychological phenomena can be fully explained in terms of biological events and by treating them as if they exist in separate realms. These approaches hold up scientific progress and have important implications for clinical practice and policy decisions (e.g., allocating research funds).


Brain Imaging, Cognitive Processes, and Brain Networks

Brian D. Gonsalves and Neal J. Cohen

The growth of neuroimaging research has led to reflection on what those techniques can actually tell us about cognitive processes. When used in combination with other cognitive neuroscience methods, neuroimaging has promise for making important advancements. For example, neuroimaging studies on memory have raised questions not only about the regions involved with memory but also about component cognitive processes (e.g., the role of different attention subsystems in memory retrieval), and this has resulted in more theorizing about the interactions of memory and attention.


Mapping Mental Function to Brain Structure: How Can Cognitive Neuroimaging Succeed?

Russell A. Poldrack

To understand the anatomy of mental functions, researchers may to need to move away from commonly used brain mapping strategies and begin searching for selective associations. This will require more emphasis on the structure of cognitive processes, which may be achieved through development of formal ontologies (e.g., the Cognitive Atlas) that will describe the "parts" and processes of the mind. Using these ontologies in combination with large-scale data mining approaches may more directly relate mental processes and brain function.


The Appeal of the Brain in the Popular Press

Diane M. Beck

Why do people like the brain so much? Brain-related articles in the press, especially ones about fMRI research, tend to be very popular with the general public, but many of these articles may result in misinterpretations of the science. Part of the popularity may be attributed to their deceptively simple message: Perform an action and a certain area lights up. In addition, people are more confident in "biological" images than in the behavioral phenomena on which the images are based. In order to maintain trust with the public, scientists have a responsibility to provide the press with descriptions of research and interpretations of results research that are clear, relevant, and scientifically accurate.


Frontiers in Human Neuroscience: The Golden Triangle and Beyond

Jean Decety and John Cacioppo

The development of neuroimaging has created an opportunity to address old questions about brain function and behavior in new ways and also to uncover new questions. The knowledge that emerges from neuroimaging studies is more likely to be beneficial when combined with techniques and analyses that break down complex constructs into structures and processes, measures that gauge neural events across different times, and animal studies.


Bridging Psychological and Biological Science: The Good, Bad, and Ugly

Arthur P. Shimamura

The advent of functional neuroimaging has brought both praise and criticism to the field of psychological science. Although most studies relying on fMRI are correlative, they do offer some clues about the biology underlying psychological processes. However, it is not sufficient to show which area of the brain is involved in a particular cognitive process; rather theories need to address "how?" questions (e.g., How does the hippocampus contribute to remembering?) in order to best bridge psychological and biological science.



Footnote

1 Also see Mind Hacks, BPS Research Digest, and Neuroskeptic.

References

Vul E, Harris C, Winkielman P, Pashler H (2009). Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition. Perspectives on Psychological Science 4(3), 274-290.

Wolfe-Simon F, Blum JS, Kulp TR, Gordon GW, Hoeft SE, Pett-Ridge J, Stolz JF, Webb SM, Weber PK, Davies PC, Anbar AD, & Oremland RS (2010). A Bacterium That Can Grow by Using Arsenic Instead of Phosphorus. Science.


Thanks to Sandra of Channel N for alerting me to the special issue.

Sunday, December 5, 2010

The Neuroscience of Kitchen Cabinetry



Neurokitchen Design is the latest fad among the rich and famous, according to a poorly researched article in the Wall Street Journal:
A Kitchen to Comfort Your Soul

Combining psychology and neuroscience, Johnny Grey is an interior designer with a special recipe

By TARA LOADER WILKINSON

'You can tell a lot about a person from their kitchen," says Johnny Grey, an award-winning interior designer specializing in "happy kitchens," a design philosophy that focuses on bringing emotional, physical and psychological well-being into kitchen planning.

. . .

Mr. Grey ... takes an unusual approach to interior design. He and his team spend up to 80 hours with clients, understanding what makes them tick, often going round for dinner and even staying over at their home. His aim? To create a domestic utopia tailored to their personality, using the principles of neuroscience, or the scientific study of the nervous system, to answer their emotional needs and subliminal desires, as well as building a seamlessly practical kitchen. It appears to work.
However, Mr. Grey does not have an EEG lab to record the brain waves of his clients, as depicted in the image above. Nor does he have access to an MRI scanner, to my knowledge. For Mr. Grey to actually use the principles of neuroscience to design customized kitchens for his clients, he would need a method that records brain activity, whether it's electrical (EEG) or hemodynamic (fMRI).

Is Neurokitchen Design the latest manifestation of explanatory neurophilia (Trout, 2008)?
Credibility is a cherished currency in science, but its cues can be counterfeit. A novel series of experiments by Weisberg and her colleagues [2008] show that non-expert consumers of behavioral explanations assign greater standing to explanations that contain neuroscientific details, even if these details provide no additional explanatory value. Here, we discuss the part that this ‘placebic’ information might play in producing a potentially misleading sense of intellectual fluency and, consequently, an unreliable sense of understanding.
Even though it's likely that Grey's [pseudo]neuroscientific analysis provides no additional explanatory value, clients will pay more for a "scientifically designed" kitchen.


A kitchen is a place where you prepare and clean up

But it's so more than that now...
"A kitchen is no longer just for cooking. Often, the only time a couple will spend together awake, is in the kitchen," says the British architect [Grey], whose clients include Apple co-founder Steve Jobs, British singer Sting and millionaire publisher Felix Dennis.
Isn't that nice! But as far as I can tell, the WSJ gets a number of details wrong in this paragraph, which nonetheless has the best quote of all:
John Ziesel [Zeisel], a San Diego-based neuroscientist [sociologist] at the Salk Institute [I could find no listing for him there], meanwhile, is researching what he refers to as measurement-based design, which shows how spaces can shape our behavior. He uses everything from hormone studies, brain scans and targeted psychological experiments to foster his research. "A kitchen is a space loaded with emotional and behavioral cues," he says. "Neuroscience can help us understand what goes on behind the shiny surfaces and layout of kitchen cabinetry."
Although they might seem to make strange bedfellows, the idea that neuroscience research can inform building design is not new. The Academy of Neuroscience for Architecture (ANFA) was founded in 2003.



The Salk Institute in La Jolla, California, that architectural monument to science overlooking the Pacific Ocean, is indeed a focal point for ANFA. Jonas Salk himself enlisted architect Louis Kahn to design a research campus with lab space that would promote collaboration and creativity. The AFNA Board of Directors includes an impressive list of neuroscientists: Tom Albright, Michael Arbib, and Fred Gage to name but a few. Salk scientists Gage, Albright, and Terrence Sejnowski were on the original Advisory Board in 2003.

In April 2004 the Dana Foundation presented a manifesto of sorts from ANFA founding president John P. Eberhard and freelance writer Brenda Patoine:
Architecture with the Brain in Mind

A soaring cathedral, a brightly lit classroom, a dim maze of hospital corridors: Most of us associate certain emotions, energy levels, and even mental states with the various spaces in which we spend our lives. What underlies these responses? How important are they? Architects and neuroscientists now beginning to grapple with those questions are coming up with discoveries that have important implications for how we design spaces as diverse as neonatal care units, schools, and residences for people with Alzheimer’s disease. The benefits of collaboration between brain science and architecture are sure to increase, writes architect John Eberhard, founding president of the new Academy of Neuroscience for Architecture. Some research even suggests that certain designed environments encourage the proliferation of new brain cells.
Five years later, the Institution of Engineering and Technology was more circumspect in its analysis of the trend:
Architecture and neuroscience

Empirical evidence demonstrating how buildings affect the function and structure of our brains is still thin on the ground. Fred Gage, a neuroscientist at the Salk Institute in La Jolla, California, says that, while architects have plenty of intuitions, the key will be to construct experiments to test the influence of the spatial environment on the brain. Despite the founding of the Academy of Neuroscience for Architecture (ANFA) in San Diego in 2003 - of which Gage is a director and past-president - “we have not yet accomplished as much as we aspired to,” he says. However, neuroscience has taught us much about how our brains construct our sense of place and how certain environments might stimulate the growth of new neurons.

Fortunately, the Architects for Functional Neurogenesis special interest group seems to have escaped unscathed.

NEXT UP: How hippocampal place cells have influenced Frank Gehry.

Reference

Trout, J. (2008). Seduction without cause: uncovering explanatory neurophilia. Trends in Cognitive Sciences, 12 (8), 281-282 DOI: 10.1016/j.tics.2008.05.004


WSJ link via @minikerri.

Credit also goes to the Human Pain Research Group for their lovely EEG figure.




You may be dreaming
You may be bleeding
You may be in this box

A kitchen is a place where you prepare
And clean up
Clean up
Clean up
Clean up

Saturday, November 27, 2010

Seizures Triggered by Strawberry Syrup


Fig 1A (modified from Blauwblomme et al., 2010). Top: coronal and lateral representation of the stereotaxic implantation scheme. Bottom: reflex seizure showing ictal onset in the right insula and secondary spreading in the hippocampus.

Reflex epilepsy is a rare neurological condition in which seizures are triggered by a specific type of sensory input (Xue & Ritaccio, 2006). The most common reflex seizures are induced by light, but other reported triggers have included reading, Mah-Jong, music, the voice of a specific television performer,1 bathing, orgasm, and eating.

The present case involved a 28 year old woman who had refractory partial seizures triggered by eating, which were preceded by an unpleasant taste in her mouth. Strawberry syrup ingestion was noted to be the easiest way to induce seizures. Nine years earlier, she had surgery to remove a vascular malformation from the right frontal operculum/insular cortex. This region contains gustatory cortex encoding for taste. Because of the uncontrolled nature of her seizures, the surgical team implanted intracranial electrodes to determine the focus of abnormal EEG activity.
Two reflex seizures to strawberry syrup intake were recorded, which started with loss of consciousness, followed by facial flushing, oro-alimentary automatisms, repeated swallowing and sialorrhoea [excessive salivation], and ended with postictal confusion and amnesia. From a visual analysis of SEEG (Fig. 1A), seizures began in the anterior inferior portion of the insula with a high-amplitude spike followed by a low-voltage high-frequency discharge with secondary spreading to the hippocampus and then to the temporal neocortex.
In the early ictal state, fast gamma band activity (30-120 Hz) showed increased power in the anterior inferior portion of the insula, accompanied by decreased power in the hippocampus.

Functional MRI was also performed during strawberry syrup intake to map gustatory cortex, and another session recorded simultaneous resting state fMRI/EEG activity.


Fig. 1C (modified from Blauwblomme et al., 2010). Overlay of fMRI and SEEG results. Left: crosshairs on the dorsolateral fronto-parietal region. Right: crosshairs on the anterior insula.

The authors reported three major findings from the fMRI/EEG mapping (see Fig 1C):
  1. The dorsolateral anterior parietal cortex showed pre-ictal γ [gamma] power decrease (red) and belonged to the fMRI gustatory network (yellow). In the vicinity, the dorsolateral posterior frontal cortex showed preictal γ power increase (magenta) and interictal fMRI/EEG activations (green).

  2. Early ictal γ power increase (cyan) showed up in the inferior/middle part of the anterior insula, which also responded to taste fMRI (yellow). A preictal increase in γ power (magenta) was observed in the upper part of the anterior insula.

  3. Hippocampus showed early ictal decrease in γ activity (blue).


The surgical team identified the specific region of the insula that was the problematic seizure focus (the middle short gyrus in cyan), and removed it. Two years later, the patient remains seizure-free, and presumably can enjoy strawberry syrup once again.


Footnote

1 The identity of said performer was revealed to be Mary Hart, host of Entertainment Tonight. From Science News (Vol. 140, No. 3, p. 45):
...the woman had seizures only while watching "Entertainment Tonight."

Systematic testing ruled out all but one of the cast members -- cohost Mary Hart, whose voice pattern consistently caused the seizures. [Dr. Venkat] Ramani prescribed anticonvulsant drugs and advised the patient not to watch the program. In the two years since, she has remained "relatively seizure free," he reports.

References

Blauwblomme, T., Kahane, P., Minotti, L., Grouiller, F., Krainik, A., Vercueil, L., Chabardes, S., Hoffmann, D., & David, O. (2010). Multimodal imaging reveals the role of γ activity in eating-reflex seizures. Journal of Neurology, Neurosurgery & Psychiatry DOI: 10.1136/jnnp.2010.212696

Xue LY, Ritaccio AL. (2006). Reflex seizures and reflex epilepsy. Am J Electroneurodiagnostic Technol. 46:39-48.