Tuesday, February 26, 2008

I Laughed, I Cried, I Bought Gatorade

Advertisers, neuroscientists combine forces to produce outlandish headlines:
Advertisers, neuroscientists trace source of emotions in brain

Tuesday, February 19, 2008

GAINESVILLE, Fla. — First came direct marketing, then focus groups. Now, advertisers, with the help of neuroscientists, are closing in on the holy grail: mind reading.

At least, that’s what is suggested in a paper published today in the journal Human Brain Mapping authored by a group of professors in advertising and communication and neuroscience at the University of Florida [Morris et al., 2008].

Not only outlandish headlines, the holy grail of "mind reading" is within the grasp of their PR department. Perhaps they should consult Shinkareva et al. (2008)...

The Florida press release continues:

The seven researchers [Morris, Klahr, Shen, Villegas, Wright, He, Liu] used sophisticated brain-scanning technology to record how subjects’ brains responded to television advertisements, while simultaneously collecting the subjects’ reported impressions of the ads. By comparing the two resulting data sets, they say, they pinned down specific locations in the brain as the seat of many familiar emotions that ripple throughout it. The feat is another step toward gauging how people feel directly through functional magnetic resonance imaging, or fMRI, and other brain-scanning technology — without relying on what they claim to be feeling, the researchers say.

“We are getting to the heart of the matter by really showing this process in the brain, and how it works,” said Jon Morris, a professor of advertising and communications and lead author of the article. “We feel that this can be used to find out what people really feel about something, whether an advertisement or any other stimulus.”

It remains to be seen, however, whether someone's fMRI results will be able to predict their future purchasing behavior, and if so, whether this predictive power will be superior to traditional (and much cheaper) marketing methods.1

OK, so what did the experiment entail? The study used a three-dimensional self-report technique to examine subjects' emotional response to TV commercials in the scanner. The specific dimensions were pleasure-displeasure, arousal-calm, and dominance-submissiveness (PAD), but emotional responses were assessed through "nonverbal" responses, not the verbal labels. Now here's where things get a bit methodologically fuzzy, so I'll just quote the authors (and ask any experts to comment pro or con):
The self-report data was derived from responses to the Advertisement Self-Assessment Manikins (AdSAM®) scale2 (Morris et al., 2005). This scale provides a nonverbal, cross-cultural, visual measure of emotional response that measures the dimensions of pleasure, arousal, and dominance, and we therefore suggest is a better tool than a verbal technique that requires respondents to cognitively translate their reactions into words before reporting their feelings.3 Thus, we postulate that this methodology, grounded in psychological literature since the 1950s, should be the basis of emotional detection in the brain.
What commercials were shown? Ads for Evian, Coke, and Gatorade, plus two public service announcements (Be a Hero and Anti-Fur). How were they chosen?
The five commercials presented were all broadcasted [sic] more than 10 years ago to avoid the likelihood of the participants having previously seen them on television.
Huh, that's interesting, because the date on the Gatorade "23 vs. 39" video at YouTube says 12/23/02, and the commercial aired during the 2003 Superbowl. Last I checked, it's not 2013, and Michael Jordan was not 39 in 1992.

Here's a description of the Gatorade commercial (Morris et al., 2008):
The fourth commercial was for the sports drink Gatorade. It showcases special effects of a 23-year-old Michael Jordan, in a Chicago Bulls uniform, playing the modern-day Michael Jordan in a one-on-one grudge match. A 1987 version of Jordan's head was digitally placed on the torso of an actual performance double playing against the real 39-year-old Jordan. The two engage in the one-on-one basketball, which shows the older-but-wiser Jordan schooling his younger, more energetic self.
On the other hand, the Mean Joe Green Coke commercial is ancient (October 1979).
It shows a young boy offering his Coke bottle outside the locker room after a football game to Mean Joe Greene of the Pittsburgh Steelers. At first Mean Joe Green politely declines but then changes his mind, accepts the Coke bottle, and passes his jersey to the young boy as a return gift.
How did the consumers, er, study participants rate the commercials?

Figure 1 (Morris et al., 2008). Each of the five commercials is represented by a different color (Teacher = blue, Evian = yellow, Coke = red, Gatorade = green, Anti-Fur = brown). Figure 1a illustrates that the Anti-Fur commercial is significantly lower than the other four commercials for the mean Pleasure scores. Figure 1b illustrates that that the Gatorade and Anti-Fur commercials combined are significantly higher than the Teacher and Coke commercials combined on mean Arousal scores.

And how about reading the minds of consumers? Quite frankly, we're not talking about fine-grained distinctions here:
The AdSAM pleasure scores of four stimuli (Teacher, Evian, Coke, and Gatorade) were significantly higher than that of the Anti-Fur commercial (see Fig. 1). The disturbing content of the Anti-Fur Commercial that included a scene showering blood most likely contributed to this intense unpleasant emotion. When the imaging data of the first four commercials were contrasted to those of the Anti-Fur commercial, significant differences were identified in brain regions that are known to be associated with emotional valence. These regions included the bilateral IFG [inferior frontal gyrus, BA47] and the bilateral MTG [middle temporal gyrus, BA21] which have been found to be associated with emotional responses. [NOTE: really? the MTG as a bastion of emotional responses?]
It might be overkill to show Figure 2, with its zany-looking hemodynamic response functions spanning 30 sec (the commercials were either 30 sec or 1 min long), or to belabor certain choices in data analysis:
A statistical threshold was set to P less than 0.052 corrected with a minimum cluster size of 150 voxels when comparing the BOLD signal between the tasks. [NOTE: p less than .052? why?]
Or you can check out activations in the ventricles on page 6 of this PDF.

Even NeuroscienceMarketing.com is skeptical:
At least as reported, the conclusions seem less than startling:

Where the researchers compared the AdSAM data on pleasure-displeasure and excitement-calm to the fMRI data, they found simultaneous spikes in four different and highly localized areas of the brain. According to the article, the findings suggest “that human emotions are multidimensional, and that self-report techniques … correspond to a specific task but different functional regions of the brain.”

At first glance, this statement seems on a par with “Hillary Clinton was found to cause negative reactions in some subjects” in terms of being blandly obvious.4


1 Although any number of neuromarketing companies would have you believe this is the case.

2 Is this an example of Subneuromarketing?® (SK)

3 This approach appears to be diametrically opposed to affect labeling.

4 See also this now-classic Neurocritic quote (about the infamous This Is Your Brain on Politics Op-Ed):
Did we really need fMRI to tell us that Mrs. Clinton should try to soften the negative responses of swing voters?

Morris JD, Klahr NJ, Shen F, Villegas J, Wright P, He G, Liu Y. (2008). Mapping a multidimensional emotion in response to television commercials. Human Brain Mapping DOI: 10.1002/hbm.20544

Unlike previous emotional studies using functional neuroimaging that have focused on either locating discrete emotions in the brain or linking emotional response to an external behavior, this study investigated brain regions in order to validate a three-dimensional construct - namely pleasure, arousal, and dominance (PAD) of emotion induced by marketing communication. Emotional responses to five television commercials were measured with Advertisement Self-Assessment Manikins (AdSAM(R)) for PAD and with functional magnetic resonance imaging (fMRI) to identify corresponding patterns of brain activation. We found significant differences in the AdSAM scores on the pleasure and arousal rating scales among the stimuli. Using the AdSAM response as a model for the fMRI image analysis, we showed bilateral activations in the inferior frontal gyri and middle temporal gyri associated with the difference on the pleasure dimension, and activations in the right superior temporal gyrus and right middle frontal gyrus associated with the difference on the arousal dimension. These findings suggest a dimensional approach of constructing emotional changes in the brain and provide a better understanding of human behavior in response to advertising stimuli.

Morris JD, Woo C, Singh AJ (2005): Elaboration likelihood model: A missing intrinsic emotional implication. J Target Meas Anal Market 14: 79-98.

Shinkareva SV, Mason RA, Malave VL, Wang W, Mitchell TM, Just MA. (2008). Using fMRI Brain Activation to Identify Cognitive States Associated with Perception of Tools and Dwellings. PLoS ONE. Jan 2;3(1):e1394.

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Sunday, February 24, 2008

Stem Cells for Peter's McStroke

Fig 3 (Daadi et al., 2008). Dispersion, engraftment and differentiation of the hNSCs [human neural stem cells] in stroke-lesioned animals.
Stem cells helped repair stroke damage in rats, early Stanford study shows


— Neural cells derived from human embryonic stem cells helped repair stroke-related damage in the brains of rats and led to improvements in their physical abilities after a stroke, according to a new study by researchers at the Stanford University School of Medicine.

This study, published in the Feb. 20 issue of the journal Public Library of Science-ONE, marks the first time researchers have used human embryonic stem cells to generate neural cells that grow well in the lab, improve a rat’s physical abilities and consistently don’t form tumors when transplanted.

Though the authors caution that the study is small and that more work is needed to determine whether a similar approach would work in humans, they said they believe it shows the potential for using stem cell therapies in treating strokes.
In the Family Guy episode entitled McStroke, Peter Griffin rescues a man from a burning building -- the fast food restaurant McBurgertown. It turns out the man is the the owner of McBurgertown, who then
offers Peter a lifetime supply of burgers as thanks for his heroism. Peter accepts this offer... However, after eating 30 burgers in one sitting, he suffers a severe stroke and is hospitalized. The entire left side of his body is paralyzed, forcing him to limp around on one leg, with his arm hanging lifelessly on his side and part of his face severely hanging over.1 This lifestyle proves to be difficult for Peter for the next three months, and he blames McBurgertown for his problems. Wondering if there is anything that can be done to return to his regular regime, he decides to give stem cell research a try and, after a mere 5 minutes, Peter returns completely fine.
"Why are we not funding this?!" he asks after walking out of the stem cell research facility, completely restored.


1 Although politically incorrect (as usual), the cartoon does a reasonable job at trying to portray hemiplegia, paralysis of one half of the body (although the Picasso-esque rendition of his facial droop is a bit much).


Daadi MM, Maag AL, Steinberg GK. (2008). Adherent self-renewable human embryonic stem cell-derived neural stem cell line: functional engraftment in experimental stroke model. PLoS ONE Feb 20; 3(2):e1644.

BACKGROUND: Human embryonic stem cells (hESCs) offer a virtually unlimited source of neural cells for structural repair in neurological disorders, such as stroke. Neural cells can be derived from hESCs either by direct enrichment, or by isolating specific growth factor-responsive and expandable populations of human neural stem cells (hNSCs). Studies have indicated that the direct enrichment method generates a heterogeneous population of cells that may contain residual undifferentiated stem cells that could lead to tumor formation in vivo. METHODS/PRINCIPAL FINDINGS: We isolated an expandable and homogenous population of hNSCs (named SD56) from hESCs using a defined media supplemented with epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and leukemia inhibitory growth factor (LIF). These hNSCs grew as an adherent monolayer culture. They were fully neuralized and uniformly expressed molecular features of NSCs, including nestin, vimentin and radial glial markers. These hNSCs did not express the pluripotency markers Oct4 or Nanog, nor did they express markers for the mesoderm or endoderm lineages. The self-renewal property of the hNSCs was characterized by a predominant symmetrical mode of cell division. The SD56 hNSCs differentiated into neurons, astrocytes and oligodendrocytes throughout multiple passages in vitro, as well as after transplantation. Together, these criteria confirm the definitive NSC identity of the SD56 cell line. Importantly, they exhibited no chromosome abnormalities and did not form tumors after implantation into rat ischemic brains and into naïve nude rat brains and flanks. Furthermore, hNSCs isolated under these conditions migrated toward the ischemia-injured adult brain parenchyma and improved the independent use of the stroke-impaired forelimb two months post-transplantation. CONCLUSIONS/SIGNIFICANCE: The SD56 human neural stem cells derived under the reported conditions are stable, do not form tumors in vivo and enable functional recovery after stroke. These properties indicate that this hNSC line may offer a renewable, homogenous source of neural cells that will be valuable for basic and translational research.

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Thursday, February 21, 2008

Hey Girl, You're Really Bad at Math!

Right? Girls are bad at math, aren't they? Former Harvard president Larry Summers seem to think so...

According to Wikipedia,
Stereotype threat is the fear that one's behavior will confirm an existing stereotype of a group with which one identifies. This fear may lead to an impairment of performance.

. . .

Stereotype threat has also been found to apply to sex differences in mathematical achievement. A common stereotype is that men have stronger abilities in mathematics than women. When women believed sex differences could be revealed by a mathematics test, the men performed better. If the test was presented as gender fair, the sexes performed equally well (Spencer, Steele, & Quinn, 1999).
[For more info, see Combating Stereotype Threat in the Wild].


So let's do a neuroimaging study (Krendl et al., 2008) with...
right-handed female undergraduates at Dartmouth College (N = 28; 14 control subjects) [who] were highly identified with math, as determined by their response to the following question: "It is important to me that I am good at math." A response of 4 or higher on a 7-point Likert scale was required for participation.
...to see what parts of the brain "light up" during stereotype threat.1 The participants were tricked into thinking the study measured "the neural mechanisms engaged in cognitive tasks that require both speed and accuracy." Half of them experienced a "threatening" condition, the other half a control condition.

How was stereotype threat induced? Why, it's our old friend the IAT (Implicit Association Test)!
In the threat condition, participants were told they were going to complete a task that would assess their "math attitudes" because "research has shown gender differences in math ability and performance." These instructions served as the primary threat induction, as previous research has suggested that reminding women of gender stereotypes in math ability activates stereotype threat (e.g., O'Brien & Crandall, 2003...). However, because this study was the first attempt to induce stereotype threat while participants were in the scanner, the second categorization task we administered in this condition was the math/arts IAT (Nosek, Banaji, & Greenwald, 2002b), in which participants categorized words as being related to math, arts, males, or females. We intended for this task to further reinforce the salience of gender stereotypes regarding math ability, and indeed, pilot testing revealed that administering this IAT was sufficient to induce the stereotype-threat effect.
The non-threatening condition was the
liberal/conservative IAT, which involved categorizing words as being related to liberals, conservatives, unpleasant, or pleasant (Nosek, Banaji, & Greenwald, 2002a). Thus, control participants received no reminder of gender stereotypes regarding math ability.
Both groups of women started out with the neutral flower/insect IAT2 followed by a set of simple difficult math problems (Time 1). Then the threat/control conditions were followed another set of more difficult math problems (Time 2). The threat manipulation did, indeed, have detrimental effects on performance [but only at p=07], as shown in the figure.

[NOTE: but why did the control group perform significantly better at Time 2, when the problems were much more difficult, than at Time 1?] CORRIGENDUM: practice effects, the problems at Time 1 and Time 2 were both difficult.

What were the fMRI results? In brief, an analysis of brain regions that were more active at Time 2 than at Time 1
...showed that the control participants recruited more left-lateralized activation in the inferior prefrontal cortex (Brodmann's area, BA 47), left inferior parietal cortex (BA 40), and bilateral angular gyrus (BA 39) over time. By contrast, the threatened participants revealed greater activity in the ventral anterior cingulate cortex (vACC; BA 32/10 [NOTE: no one would call BA10 the vACC ]) on the second test than on the first (Fig. 2).
What does it all mean? From philidendron:
MC overheard two of her students discussing math class last week.

Girl 1: "Damn girl. I thought you dug math."

Girl 2: "Hell no. Girl? (tongue-click) Hell no. Hell times hell to the hell-powered no! Damn!"


1 Why?? you may ask.
In order to effectively override the stereotype-threat phenomenon, it is vital to understand clearly the core processes that underlie it. In pursuing this goal, researchers may benefit from using neuroimaging to identify brain regions engaged during stereotype threat.
2 In the flower/insect IAT,
The categories are presented in congruent blocks (i.e., "flowers" and "pleasant" paired together) and incongruent blocks (i.e., "insects" and "pleasant" paired together). Categories that were paired together were presented on the same side of the screen, and participants were required to use the same response key to categorize stimuli belonging to these categories (e.g., when "flowers" and "pleasant" were paired, participants pressed the same key to categorize the word tulip as a flower and to categorize the word rainbow as pleasant); implicit bias was measured by calculating the difference in response times between the congruent and incongruent blocks.

Krendl AC, Richeson JA, Kelley WM, Heatherton TF. (2008). The Negative Consequences of Threat: A Functional Magnetic Resonance Imaging Investigation of the Neural Mechanisms Underlying Women's Underperformance in Math. Psychological Science, 19(2), 168-175. DOI: 10.1111/j.1467-9280.2008.02063.x

This study used fMRI to identify the neural structures associated with women's underperformance on math tasks. Although women in a control condition recruited neural networks that are associated with mathematical learning (i.e., angular gyrus, left parietal and prefrontal cortex), women who were reminded of gender stereotypes about math ability did not recruit these regions, and instead revealed heightened activation in a neural region associated with social and emotional processing (ventral anterior cingulate cortex).

Links to Math Girl episodes are on the website of Dr. Veselin Jungic in the Department of Mathematics at Simon Fraser University.

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Sunday, February 17, 2008

The Sexual Allure of Chanel No. 5

Does olfactory stimulation influence sexual responsiveness in humans? More specifically, does the scent of a woman's perfume produce sexual arousal in men? If so, what are the neural correlates of this response? The answers, of course, are of great interest to the manufacturers of perfumes and fragrances, a $5 billion retail industry.

A group of Korean researchers (Huh et al., 2008) conducted a small fMRI study in 8 male subjects to examine these questions. What was the arousing fragrance, need you ask?1 According to MTV3.fi [as far as I can tell, since the article is in Finnish], it appears that the researchers used iconic perfume Chanel No. 5 as their olfactory stimulus:

Osa naisista käyttää hajuvettä oman itsensä vuoksi. On yksinkertaisesti miellyttävää tuoksua hyvälle. Toisaalta tietoisuus siitä, että on hyvätuoksuinen, lisää itsetuntoa. Hajusteilla pyritään tekemään myös positiivinen vaikutus vastakkaiseen sukupuoleen. Onko hajusteilla kuitenkaan moista voimaa, vai onko niiden teho lähinnä plasebon luokkaa? Vaikuttavatko hajusteet ainoastaan käyttäjänsä mielikuviin, vai onko niillä todellista tehoa? Moisiin kysymyksiin halusivat saada selon muun muassa korealaisen Chonnamin yliopiston tutkijat Joon Huh ja Kwangsung Park.

Tutkimukseen osallistui kahdeksan 20–35-vuotiasta miestä. He haistoivat kaksi kertaa 30 sekunnin ajan naisten hajuvettä. Haisteluiden välillä oli 30 sekunnin mittainen tauko. Haistelusessioiden jälkeen koehenkilöiden aivoista otettiin magneettikuvat, jotta nähtäisiin, mitkä aivojen kohdat reagoivat hajuveden haistamiseen. Magneettikuvauksen jälkeen miesten tuli listata mielipiteensä hajuveden voimakkuudesta ja siitä, miten hajuvesi vaikutti heihin seksuaalisesti. Testissä käytetty hajuvesi oli muuten Chanel No. 5 joten nyt näemme, onko esimerkiksi Marilyn Monroen suosimasta tuoksusta mihinkään.

The fMRI study used a block design of alternating 30 sec intervals of olfactory stimulation and rest (Huh et al., 2008) . After the scanning session, subjects rated their perceived sexual arousal and the odor's intensity. Two of the eight subjects reported "strong" sexual arousal, three reported "moderate" sexual arousal, and three were presumably not aroused while smelling Chanel No. 5. The imaging results demonstrated that
The common brain areas activated in response to the odor stimulus in all eight subjects included the insula, the inferior and middle frontal gyrus, and the hypothalamus. The median [sic] cingulate gyrus, thalamus, angular gyrus, lingual gyrus, and cerebellar cortex were activated in subjects who had moderate or strong sexual arousal response.

Huh, so why were portions of the parietal and occipital lobes activated by an olfactory stimulus? I don't know the authors' interpretation, but one speculation for the latter is that the perfume might have triggered some visual associations, perhaps with an ad campaign or a specific person.

However, these results are very preliminary, given the small number of subjects (and the paltry numbers at each level of sexual arousal).

Who funded this research? IDK yet. But interestingly, Korea is a leader in olfactory branding:
Presidential Candidate Lures In Voters with Great Korea Perfume

In Korea, presidential front-runner Lee Myung Bak must have a keen nose and believe in the powers of olfaction like no other since his campaign staff has decided to implement a very unusual strategy for "branding" the candidate's image. Drawing on marketing experience and department-stores' olfactory branding of which Korea is an early practitioner, the idea has been taken a step further by attempting to associate feelings of "hope, victory, passion" with a perfume called Great Korea that was secretly sprayed at public gatherings and will be again sprayed when voters enter the polling booths. ...

The semi-covert operation called "The Perfume of the President" has a Big-Brother flavor to it and seemed not long ago to be safely relegated to the realm of science-fiction but its has been conducted for real since the beginnings of the presidential campaign and will be ultimately tested on December 19, 2007 when voters make their ways to the voting urns. Lee Myung-Bak has already a 30-point advance in the polls.
Maybe the next fMRI study will examine the brain activity elicited by Great Korea perfume...


1 I didn't have access to the entire article in the Journal of Sexual Medicine and was therefore reliant on other sources.


Huh J, Park K, Hwang IS, Jung SI, Kim H-J, Chung T-W, Jeong G-W. (2008). Brain activation areas of sexual arousal with olfactory stimulation in men: A preliminary study using functional MRI. J Sex Med., in press.

Introduction. There have been extensive studies evaluating the functional neuroanatomy of the brain during visual sexual stimulation. However, little data exist concerning the role of olfactory stimulation in human sexuality.
Aim. This preliminary study intended to elucidate the brain areas responding to an olfactory sexual stimulus using functional magnetic resonance imaging (fMRI).
Methods. Eight healthy right-handed heterosexual male volunteers (20–35 years of age), having normal olfaction and no brain diseases, were recruited. During fMRI, a women's perfume was given as an olfactory sexual stimulant in an alternating block design with a 30-second stimulation period followed by a 30-second rest. After the fMRI sessions, the participants provided ratings for both the odorant's intensity and perceived arousal.
Main Outcome Measures. The study subjects rated the odorant stimulation and perceived sexual arousal response by Likert-type rating scales. Brain activation maps were made by blood oxygenation level-dependent (BOLD)-based fMRI with an echo-planar imaging pulse sequence.
Results. Two out of eight subjects experienced "strong" sexual arousal, and three subjects experienced "moderate" arousal during olfactory stimulation, resulting in a mean score of 2.25 on a 4-point scale. The common brain areas activated in response to the odor stimulus in all eight subjects included the insula, the inferior and middle frontal gyrus, and the hypothalamus. The median cingulate gyrus, thalamus, angular gyrus, lingual gyrus, and cerebellar cortex were activated in subjects who had moderate or strong sexual arousal response.
Conclusion. Olfactory stimulation with women's perfume produces the activation of specific brain areas in men. The brain areas activated differed according to the degree of perceived sexual arousal response. Further studies are needed to elucidate brain activation response according to the different kinds and intensities of olfactory stimulation.

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Thursday, February 14, 2008

For the Perez Hilton of Academic Neuroscience Podcast Gossip,

see Neurology podcasts - the shocking truth.

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Sunday, February 10, 2008

I'm Too Sexy For My Brain Too Sexy For My Brain

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A Health Club for Your Brain

I’m too sexy for my car too sexy for my car
Too sexy by far
And I’m too sexy for my hat
Too sexy for my hat what do you think about that

I'm Too Sexy
---Right Said Fred

...and speaking of sexy, click here for vB™'s Valentine's Day specials!

-via a savvy anonymous tipster

I’m a model you know what I mean
And I do my little turn on the catwalk
Yeah on the catwalk on the catwalk yeah
I do my little turn on the catwalk

I'm Too Sexy
---Right Said Fred

The Vanishing Point - Artem Emelianov (R) represents the new breed of anorexic male models.

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Thursday, February 07, 2008

Double-Blind Bind

An editorial on peer review was published today in Nature, and the text is reprinted in their Peer-to-Peer blog. The editors are soliciting comments and suggestions, and so far the count is up to 25 48.
Working double-blind

Should there be author anonymity in peer review?

Double-blind peer review, in which both authors and referees are anonymous, is apparently much revered, if not much practised. The Publishing Research Consortium (PRC) has assessed attitudes towards peer review among 3,000 academics in an international survey across the sciences and humanities. ...71% have confidence in double-blind peer review and 56% prefer it to other forms of review. Support is highest with those who have experienced it (the humanities and social sciences) or where it is perceived to do the most good (among female authors). The least enthusiastic group is editors. So is it time for editors, and those at Nature in particular, to reconsider their position?

If referees know the authors' identities, it may leave the latter vulnerable to biases about them or their previous work, their gender, their nationality or their being new to an area of research. But the PRC survey supports the contention of Nature and others that identifying authors stimulates referees to ask appropriate questions (for example, differentiating between a muddy technical explanation and poor experimental technique). Knowing author identities also makes it easier to compare the new manuscript with the authors' previously published work, to ensure that a true advance is being reported. And knowing rather than guessing the identities of authors encourages reviewers to raise potential conflicts of interest to the editors.
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 and Peer Review Trial and Debate at Nature).

Commenter Nina Papavasiliou puts forth another interesting proposal:
Is double blind (or even open) review a cure-all? Not necessarily, and there are definitely good reasons to argue for/against both options (including but not limited to the reasons you mention). But here's another thought, that comes from being on NIH review panels: What if review is changed by having each reviewer identity and their comments blogged to one another before a decision on the paper is reached? That will a) stop reviewers from making silly comments (from asking for ridiculous experiments to killing the paper with a couple of unsubstantiated lines like "I see nothing new here" - as they will not be hiding behind anonymity in their reviewer group) and b) may even increase the quality of papers (as reviewers could, in real time, convince one another and reach consensus prior to a decision).
She also describes the disadvantages of being a junior investigator, one who would benefit from double-blind review.

Peer review can be more or less biased depending on field. I "live" in a field where it is indeed extremely biased but not against sex - rather there is direct bias (both by editors and also by reviewers) against junior faculty combined with a relatively free ride for senior faculty. Of course, this is anecdotal, but a study on the issue broken down by field will, I think, be far more informative.

Many junior faculty in my field have direct experience of this bias in peer review. How else would you call it when a paper with a set of data but junior authors is rejected by the journal (e.g. Nature) without review, when the IDENTICAL results (authored by very senior authors) are reviewed by the same Editor and published with much fanfare? (This has happened to me twice, and if you are interested I can substantiate with exact publications, dates etc).

CLARIFICATION: Dr. Papavasiliou doesn't think that being female is as great a disadvantage in her field as seniority. However, a recent paper showed that in another field (ecology and evolutionary biology), double-blind review benefits women to a significant extent (Budden et al., 2008 -- read a good summary here).


Budden A, Tregenza T, Aarssen L, Koricheva J, Leimu R, Lortie C. (2008). Women, Science and Writing. Trends in Ecology & Evolution 23:4-6.

Editorial. Working double-blind. Nature 451; 605-606; 2008.

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Remembering Hypothalamic DBS

In an ever-lengthening list of recently reported "miracle cures" for Alzheimer's disease [see also perispinal etanercept and the magic NIRS helmet], do we have
Hope for Alzheimer's? Deep Brain Stimulation
Electrical Currents in the Brain May Help Patients Locate Lost Memories

ABC News Correspondent
Jan. 30, 2008

Researchers report what they say is a world first: By implanting a device in a man's brain, they have improved his memory. The discovery, published today in the Journal of Neurology [uh, no it's in the Annals of Neurology -- the "Journal of Neurology" doesn't exist], raises the possibility of using this technique to treat Alzheimer's patients.

Surgeons made this accidental discovery while a 50-year-old-male patient was undergoing "deep brain stimulation," as part of an experimental treatment for obesity.

With the patient under local anesthesia, but fully awake, surgeons traveled into the deepest recesses of the brain, moving gingerly at a quarter of an inch an hour, listening to electrical "pulses," as millions of brain cells communicated with each other.

. . .

Surgeons treating the obese patient hoped that adding electrical signals to his brain would regulate his appetite.

But amazingly, in the midst of the operation, something completely unexpected happened. The patient suddenly reported a flood of intricately detailed memories from an incident decades ago.
Yes, you say. So what, that was a week ago (Hamani et al., 2008) -- time to move on to the next miracle cure. However, most of the points I want to make here haven't been made in other posts on the topic.

(1) This is the first time that DBS of the hypothalmus has been performed on a human to treat obesity. In recent animal studies, the specific target nuclei have been the lateral hypothalamus in rats (Sani et al., 2007) and the ventromedial hypothalamus in monkeys (Laćan et al., 2008).
Hypothalamic stimulation was proposed based on experimental studies of appetite control in rodents, dogs, and nonhuman primates (Stenger et al., 1991; Brown et al., 1984; Takaki et al., 1992), and the experience, albeit limited, of hypothalamotomy for obesity in humans (Quaade et al., 1974; Quaade, 1974).
(2) The memory-enhancing effects were thought to result from stimulation of the fornix, not the hypothalamus. The fornix is a fiber bundle that connects the hippocampus to the mammillary bodies and septal nuclei.

But first, a brief case history:
A 50-year-old man with a life-long history of obesity (420 pounds/190.5 kg; body mass index, 55.1 kg/m) did not respond to multiple treatments, including dietary regimens, psychological interventions, group therapies, and medications. Medical comorbidities included type II diabetes, hypertension, and obstructive sleep apnea. He refused gastric bypass and bariatric surgery believing that he would continue to eat excessively despite these interventions. Given his resistance to treatment, the concern with the long-term health consequences of morbid obesity, and our group's long-standing interest in functional neurosurgery and DBS, he was referred to consider the possibility of a neurosurgical treatment.
We know he experienced...
"déjà vu" with stimulation of the first contact tested (contact 4: 3.0 volts, 60-microsecond pulse width, and 130Hz). He reported the sudden perception of being in a park with friends, a familiar scene to him. He felt he was younger, around 20 years old. He recognized his epoch-appropriate girlfriend among the people.
...which held up under double-blind conditions. He also showed improved performance on standardized neuropsychological tests of memory.

(3) However, there were adverse effects at some of the stimulation sites:
At certain contacts, at intensities of 5 volts or greater, he experienced stimulation dose-dependent adverse effects, including feeling an unpleasant generalized warming sensation that was followed by facial hyperemia and sweating. There were no overt associated changes in the monitored vital signs (blood pressure, heart rate, and electrocardiogram). In addition, when stimulation was rapidly increased from 0 to 5 volts at the most ventral contacts, in closest proximity to the optic tracts, the patient transiently saw flashes of light in the contralateral visual field consistent with current spread to the ipsilateral optic tract.
(4) Because of his weight, the patient could not have MRI or PET scans, but he could (and did) have CT and EEG.

Supplementary Figure (Hamani et al., 2008). Location of DBS electrodes in the hypothalamus. Post-operative CT image at the level of contacts 0 and 4. (A) Electrode locations mapped onto a brain atlas 9 shown in coronal (B) and axial planes (C). The electrode contacts that most readily induced déjà vu experiences with stimulation (0,1 and 4,5) were in close proximity to the fornix (arrows). Red circles - Right electrode contacts 0 and 1. Blue circles - Left electrode contacts 4 and 5. Cm- corpus mammilare; Dm- nucleus dorsomedialis; Fx- fornix; Hpth- hypothalamus...

(5) But most importantly, did DBS help the patient lose weight?
There were no reproducible changes in his subjective sensation of hunger with stimulation on a self-rated 1 to 10 scale with these settings.
So was the procedure helpful at all in treating the patient's obesity? Did he lose any weight? One has to go to the Supplementary Materials to find the answer (which is no, he didn't lose weight...or at least, he gained back all 26.5 lbs):
Change in weight was the primary measure used to evaluate the effectiveness of hypothalamic stimulation on obesity. There was no weight change in the first 6 months of DBS using subliminal monopolar stimulation at high frequency (130 Hz)... Because of the important relationship between stimulation frequency and clinical benefit in other conditions, we then tried stimulation at a lower frequency, 50 Hz... With this new setting, the patient lost 12 kg over 5 months with no clear change in diet or exercise habits. He reported reduced food cravings and a decreased tendency to binge with stimulation. In the last 4 months however, the patient purposely turned the stimulator off some evenings using the hand held controller because he had a desire to eat and he felt it might help him sleep. With the stimulator turned off, nighttime binging activity returned as before surgery and he regained the weight he had lost. Fifteen months after stimulation, his weight was 192 Kg [a net gain of 1.5 kg].
But his California Verbal Learning Test scores were significantly improved!


Hamani C, McAndrews MP, Cohn M, Oh M, Zumsteg D, Shapiro CM, Wennberg RA, Lozano AM. (2008). Memory enhancement induced by hypothalamic/fornix deep brain stimulation. Annals of Neurology, 63(1), 119-123. DOI: 10.1002/ana.21295

Bilateral hypothalamic deep brain stimulation was performed to treat a patient with morbid obesity. We observed, quite unexpectedly, that stimulation evoked detailed autobiographical memories. Associative memory tasks conducted in a double-blinded "on" versus "off" manner demonstrated that stimulation increased recollection but not familiarity-based recognition, indicating a functional engagement of the hippocampus. Electroencephalographic source localization showed that hypothalamic deep brain stimulation drove activity in mesial temporal lobe structures. This shows that hypothalamic stimulation in this patient modulates limbic activity and improves certain memory functions.

Laćan G, De Salles AA, Gorgulho AA, Krahl SE, Frighetto L, Behnke EJ, Melega WP. (2008). Modulation of food intake following deep brain stimulation of the ventromedial hypothalamus in the vervet monkey. J Neurosurg. 108:336-42.

Sani S, Jobe K, Smith A, Kordower JH, Bakay RA. (2007). Deep brain stimulation for treatment of obesity in rats. J Neurosurg. 107:809-13.

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Tuesday, February 05, 2008

So shave your face with some mace in the dark

The Failure Of Man
Details the failure of man in every dispensation.

from Dispensational Charts
by Clarence Larkin

The books and charts by Clarence Larkin have been extremely helpful to Christians since they were first published over 75 years ago. They have passed into the public domain and we are making some of the charts available here as an aid to Bible study. Larkin's charts are well thought out and Scriptually sound. Some of the more detailed are books in themselves. They reveal Larkin's vast knowledge of the Scriptures and phenomenal grasp of prophecy.

Kill the headlights and put it in neutral
Stock car flamin’ with a loser and the cruise control
Baby’s in reno with the vitamin d
Got a couple of couches, sleep on the love-seat


"Anonymous" protest on February 10.

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Monday, February 04, 2008

30 is the new 70

44 is the age of depression, say researchers

By Richard Alleyne

The biggest lows of our lives are experienced in middle age, according to new research that concludes that Britons are at their most depressed aged 44.

Scientists believe that although we are closer to death as pensioners and powerless in youth, it is the "reality check" years of our 40s that are the most depressing.
I'm not writing about that article, which was based on a finding to appear in the journal, Social Science & Medicine (available online as a preprint on David G. Blanchflower's website). Instead, this post is about another downhill slide that does not recover as one ages.

A new imaging paper applied the technique of deformation field morphometry 1 to the MR images from a group of male subjects 18-51 years to quantify the effects of aging on neuroanatomical regions of interest (Pieperhoff et al., 2008). Although this paper is notable for technical reasons, it isn't the first to demonstrate how much your brain deteriorates by the age of 30 (e.g., Gur et al., 2002; Fotenos et al., 2005). In fact, the latter authors noted that
Whole-brain volume differences were detected by age 30.

Figure 2 of Pieperhoff et al., 2008. Horizontal sections of the reference brain with statistical maps, showing the t values of age-related volume decline and increase. t values were calculated by a two-sided t test for a linear regression in the voxels of the LVR [local volume ratio] maps, depending on age. The statistical map is thresholded according to a significance level of p less than .01.

The latest findings, in brief:
Age-related volume declines in circumscribed brain regions are detected, which are part of functionally defined systems, i.e., the sensorimotor system, encompassing the cerebellum, thalamus, somatosensory and motor cortices, and the prefrontal system, encompassing the anterior cingulate as well as the lateral and basomedial frontal cortices. Regions belonging to other functional systems, such as the auditory system or the visual system, did not show such age–volume relationships.
The ventricles showed a pronounced widening. Remarkably, these volume differences occur at a relatively early period of the human life span.
So maybe the hippies were right when they said, "don't trust anyone over 30"...


1 According to the authors:
Deformation field morphometry (DFM) is a highly automatized technique based on the nonlinear transformation (i.e., registration) of individual three-dimensional (3D) magnetic resonance (MR) images to a reference image. Each "source" MR image is warped to a reference image such that the differences between them are minimized, yielding a deformation field. The analysis of deformation fields enables quantification of the shape of human brains at the voxel level. Thus, this technique has the potential to detect local structural differences between brains. Various algorithms based on substantially different mathematical approaches have been proposed for DFM. The accuracy of the registrations may differ significantly between currently used algorithms (Crivello et al., 2002). In the present study, we applied an algorithm that is based on an elastic, nonlinear deformation of the source MR images (Hömke, 2006).

Fotenos AF, Snyder AZ, Girton LE, Morris JC, Buckner RL. (2005). Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD. Neurology 64:1032-9.

Gur RC, Gunning-Dixon FM, Turetsky BI, Bilker WB, Gur RE. (2002). Brain region and sex differences in age association with brain volume: a quantitative MRI study of healthy young adults.
Am J Geriatr Psychiatry 10:72-80.

Pieperhoff P, Homke L, Schneider F, Habel U, Shah NJ, Zilles K, Amunts K. (2008). Deformation Field Morphometry Reveals Age-Related Structural Differences between the Brains of Adults up to 51 Years. Journal of Neuroscience, 28(4), 828-842. DOI: 10.1523/JNEUROSCI.3732-07.2008

Age-related differences in the anatomical structure of the brains from 51 healthy male subjects (age: 18-51 years) were analyzed by deformation field morphometry in a cross-sectional study. The magnetic resonance images of the brains were nonlinearly registered onto the image of a reference brain: the registration algorithm simulated an elastic deformation of each brain (source brain) so that the voxelwise intensity differences with the reference brain were minimized. A three-dimensional deformation field was calculated for each source brain that encoded the anatomical differences between the source brain and the reference brain. Maps of voxelwise volume differences between each subject's brain and the reference brain were analyzed. They showed age-related differences in anatomically defined regions of interest. Major volume decreases were found in the white matter and nuclei of the cerebellum, as well as in the ventral thalamic nuclei and the somatosensory and motor cortices, including the underlying white matter. These findings suggest that aging between the second and sixth decade predominantly affects subcortical nuclei and cortical areas of the sensorimotor system, forming the cortico-rubro-cerebello-thalamo-cortical pathway. Additionally, a pronounced age-related decline in volume was observed in the rostral anterior cingulate, orbitofrontal, and lateral prefrontal cortices. Almost no differences were observed in the occipital and temporal lobes. The ventricles showed a pronounced widening. Remarkably, these volume differences occur at a relatively early period of the human life span. It may be speculated that these structural differences accompany or precede differences in sensorimotor functions and behavior.


Blanchflower DG, Oswald AJ (in press). Is Well-being U-Shaped over the Life Cycle?
Social Science & Medicine, 2008.

We present evidence that psychological well-being is U-shaped through life. A difficulty with research on this issue is that there are likely to be omitted cohort effects (earlier generations may have been born in, say, particularly good or bad times). First, using data on 500,000 randomly sampled Americans and West Europeans, the paper designs a test that can control for cohort effects. Holding other factors constant, we show that a typical individual’s happiness reaches its minimum -- on both sides of the Atlantic and for both males and females -- in middle age. Second, evidence is provided for the existence of a similar U-shape through the life-course in East European, Latin American and Asian nations. Third, a U-shape in age is found in separate well-being regression equations in 72 developed and developing nations. Fourth, using measures that are closer to psychiatric scores, we document a comparable well-being curve across the life cycle in two other data sets: (i) in GHQ-N6 mental health levels among a sample of 16,000 Europeans, and (ii) in reported depression and anxiety levels among 1 million U.K. citizens. Fifth, we discuss some apparent exceptions, particularly in developing nations, to the U-shape. Sixth, we note that American male birth-cohorts seem to have become progressively less content with their lives. Our paper’s results are based on regression equations in which other influences, such as demographic variables and income, are held constant.

Figure 1 of Blanchflower & Oswald, in press. The incidence of self-reported depression in the UK Labour Force Survey. Here the data are pooled for men and women across the period 2004Q2-2007Q1. The sample is for those aged 16-70. There are approximately one million observations (n=972,464), and the estimates are weighted using the person weights so are nationally representative.

Figure 3 of Fotenos et al., 2005. Cross-sectional and longitudinal plots of whole-brain volume, normalized for head size. (A) Cross-sectional plot of normalized whole-brain volume (nWBV) across the adult lifespan. The line represents the best-fit polynomial regression of all nondemented individuals and is referred to as the cross-sectional, nondemented aging curve.

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Friday, February 01, 2008

Millions Like Stars In My Hands, Daggers In My Heart, Wage War

Iraq Conflict Has Killed A Million Iraqis: Survey

LONDON - More than one million Iraqis have died as a result of the conflict in their country since the U.S.-led invasion in 2003, according to research conducted by one of Britain’s leading polling groups.

The survey, conducted by Opinion Research Business (ORB) with 2,414 adults in face-to-face interviews, found that 20 percent of people had had at least one death in their household as a result of the conflict, rather than natural causes.

The last complete census in Iraq conducted in 1997 found 4.05 million households in the country, a figure ORB used to calculate that approximately 1.03 million people had died as a result of the war, the researchers found.

The margin of error in the survey, conducted in August and September 2007, was 1.7 percent, giving a range of deaths of 946,258 to 1.12 million.
. . .

Published on Thursday, January 31, 2008 by Reuters

And to follow up the grim post about PTSD and violence is an outstanding summary of the mental health crisis plaguing the Army. In Mental Health and the Rapidly Breaking Army, Mike Dunford describes of series of articles in the Washington Post about the rapid rise in suicide attempts/self-injuries and in particular, the sad case of US Army 1st Lt. Elizabeth Whiteside:
In the note that she wrote before swallowing whatever pills she had around her, she said that she was "very disappointed in the Army". It's hard to find any reason for her not to be disappointed. The Army's treatment of her has been absolutely abysmal. Unfortunately, the same can be said for many other soldiers and veterans. Although the Army has been working to improve mental health care, the system is not where it needs to be, and faces no shortage of hurdles along the way.

Around me the grass was burning. I crouched down and waited. The sheet of fire retreated.

I will carve my own heart and serve myself to God

-Single Gun Theory, Angels Over Teheran

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