Friday, December 28, 2007

"Tabloid Language" in Nature Neuroscience

Disco Drosophila

By now, everyone has read about the so-called "homosexual" (actually bisexual) fruit flies (Grosjean et al., 2007):1
Study finds gay gene in fruit flies

SUMMARY: Scientists have found that a gene can turn on and off homosexual impulses in fruit flies.

Researchers in Chicago have discovered a gene that identifies homosexuality in fruit flies, which can be turned on and off with drugs. David Featherstone, a biologist at the University of Illinois, said that while humans have a similar gene, it has yet to be determined whether that gene has any effect on same-sex attractions in humans.
It's not surprising that the popular press used tabloid terminology to sell the story. But how many of you have seen the highly critical News and Views article by Joel D. Levine in the January 2008 issue of Nature Neuroscience? He calls Grosjean et al. on the carpet for using sensationalistic language, which the editors and reviewers apparently allowed into the final version of the manuscript.
Glia and romance

Drosophila courtship is a complex behavior. A new study shows that glia modulate neurotransmission to influence male preference, but the authors should have resisted the temptation to describe their results in tabloid language.

...In the current issue, Grosjean et al. describe an unexpected role for glial cells in the initiation of male courtship behavior. A mutation that reduces expression of a glial amino-acid transporter causes male flies to court other males with the same probability as females. The authors accordingly named this transporter genderblind. The courtship behavior associated with the genderblind mutation is certainly different from control behavior, but is it really homosexual?
. . .

The study by Grosjean et al. makes an important contribution by calling attention to a neuro-glial element in the circuitry that governs courtship behavior. Furthermore, this study initiates the search for the glutamatergic neurons involved in the processing of courtship pheromones.

Apart from its merits, however, this paper has a serious language problem. Throughout, the authors use the term homosexual to describe the behavior of a male mutant that courts both males and females with equal probability. If anything, these flies might be bisexual, but the data are also consistent with the possibility that genderblind mutants would court anything painted with 7-tricosene...
. . .

...bizarre misapplication of fruit fly research spilling into the public and political arena may well be fostered by scientists' increased use of tabloid language. Yes, the business of science requires communicating effectively, raising money, and indeed a form of advertising, but the language in scientific papers must stick to the facts. My argument is not at all about political correctness. The misuse of a term like homosexual in this and other cases is simply inaccurate, unnecessary, and, in the end, bad for the scientific business.
You have to give the editors some credit, though, for publishing Levine's critique, although it would've been more fun if they let flyingkumquat write the rejoinder instead:
I have had enough of the "OMG You Can Turn Fruit Flies Gay and Then Straight Again" silliness.

Some fishes can change their sex. I don't see people saying, "OMG Fishes Can Change Their Sex, Maybe We Can Too!"

Perhaps a new section of the journal can be called Dish and Bitch...


Footnote

1 For an excellent summary of courtship in the genderblind mutant, see Bisexual flies and the neurochemistry of behavior. See also Wait for it...Wait for it...It's Teh Gay Gene!


References

Grosjean Y, Grillet M, Augustin H, Ferveur J-F, Featherstone DE. (2007). A glial amino-acid transporter controls synapse strength and homosexual courtship in Drosophila. Nature Neurosci. 11:54-61.

Levine JD (2008). Glia and romance. Nature Neurosci. 11:8-10.

Wednesday, December 26, 2007

NIH and Physical Sciences Budgets Take a Hit


Sledge hammer hits large mass resting on person.
From:
UCB Physics Lecture Demonstrations.

News
Budget blow to US science

Physics takes a hit despite earlier promises.

by Eric Hand

. . .

The spending bill marks the end of the annual budget wrangling in Congress (see Nature 449, 962; 2007). It includes spending for all government departments other than defence, which has already been approved. The final numbers for fiscal year 2008 include what amounts to a 0.5% increase for the National Institutes of Health (NIH), less than one-sixth of the rise that Congress had sought in an earlier, unsuccessful bill. Within the physical sciences, programmes in high-energy physics and fusion are hit particularly hard. "This is probably the worst budget for science that anyone can remember," says Michael Lubell, a spokesman at the American Physical Society in Washington DC. "It absolutely devastates and probably wipes out American high-energy physics."

Nature 451:2-3 (2007).

CERN - the European Organization for Nuclear Research

Saturday, December 22, 2007

Sneezing etiquette and the efficacy of masks


Fig 1 (Granville-Chapman & Dunn, 2007). Sneeze without a surgical mask: lateral view.

More fun from the Christmas issue of the British Medical Journal.
Mixed messages
Excuse me!
J Granville-Chapman and R L Dunn review the etiquette of sneezing in surgical masks

Sneezing etiquette and the efficacy of masks in the operating theatre remain a subject of debate. Standard teaching dictates that one must face the wound when sneezing, so that droplets escape backwards, via the sides of the mask. A literature search found no clear demonstration of this principle.

We therefore tested the hypothesis that one should face the wound when sneezing into a surgical mask in theatre.

Fig 3 (Granville-Chapman & Dunn, 2007). Sneeze with a surgical mask: lateral view.

The verdict?
Our photographs show that the most important visible escape of spray comes from below the mask on to the surgeon’s chest. We therefore recommend that surgeons should follow their instincts when sneezing during operations.
Reference

Granville-Chapman J, Dunn RL. (2007). Excuse me! BMJ 335:1293.

Friday, December 21, 2007

Sex, aggression, and humour: responses to unicycling


Juggling unicyclist and UTSA graduate Ian Bexar Maurer-Stothert

'Tis the season for the British Medical Journal's satire issue to lighten the holiday mood. Last year's gems included 2007 Ig Nobel Prize winner, Sword Swallowing and Its Side Effects (Witcombe & Meyer, 2006) and Phenotypic differences between male physicians, surgeons and film stars: comparative study by Trilla and colleagues (aka, Are Surgeons Taller And Better Looking Than Other Doctors?).

This year, Sam Shuster compared men and women’s responses to the sight of a unicyclist:
After retiring from a busy university department in Newcastle upon Tyne, and with the time and the need for more than the usual consultancies, I was able follow some of my more extreme inclinations. As a cyclist, I had occasionally thought of using more or fewer wheels, but it was only when choosing a grandson’s gift that I got seriously lost in contemplation of a gleaming chrome unicycle. My wife said "buy the bloody" thing, which I did on the whim of the moment. After months of practice at home, I graduated to back streets, a small paved park, and finally town roads. I couldn’t avoid being noticed; in turn, I couldn’t avoid observing the form that notice took. Because at the time there were no other unicyclists in the area, such sightings would have been exceptional, yet I soon found that the responses to them were stereotyped and predictable. I realised that this indicated an underlying biological phenomenon and set about its study.

This is not Dr. Shuster, but rather a participant in the July 29, 2005 Critical Mass ride in Vancouver. One might imagine that he received a particularly hostile reception from stranded heterosexual male motorists 15-35 years of age.

After compiling the comments of over 400 people, Dr. Shuster reported the following:
Almost 50% of those encountered, more often men than women, responded verbally. The sex difference in the type of response was striking. Around 95% of responses from women praised, encouraged, or showed concern, and women made few comic or snide remarks. In contrast, only 25% of the comments made by men indicated praise, appreciation, or neutrality, whereas 75% were attempts at comedy, often snide and proffered combatively as a put-down.
Some of the choice comments included:
Inquisitive 5-12 year olds:
"Why do you use only one wheel?"

Aggressive boys:
"Do you want to knock him over?" "Yes I bet I could do it"

Women:
"Wonderful . . . I am impressed"
"Clever, clever"
"You are an Olympic champion"

Men:
"Couldn’t you afford the other wheel?"
"Where’s the other bits then?"
"You must like living dangerously"

Elderly men
Two men walking together asked seriously, not as a joke, "Are you practising for a circus then?" and "Does it crush your bollocks mate?"
And what about sex and aggression? Was there any relationship with testosterone levels?

From about 11-13 years, boys began to develop an aggressive response, which continued throughout the school years. They tried to put me off balance by suddenly shouting, jumping out of hiding, kicking a football, throwing stones, or riding a bicycle at me; a few asked for a ride in addition to aggressive behaviour.

A further change in male behaviour was seen during the late teens—aggression decreased, but they tried to make disparaging "jokes," which were sometimes incorporated into mocking songs. This change continued, and finally evolved into adult male humour with its concealed aggression.

The female response was subdued during puberty and late teens, with apparent indifference or minimal approval, such as a tentative smile. It then evolved to the laudatory and concerned adult female response.
Estimated changes in serum testosterone concentrations in males with age
Particularly interesting for the evolution of humour was the way the initial aggressive intent channelled the verbal response into a contrived but more subtle and sophisticated joke, in which aggression is concealed by wit. This shows how the aggression that leads to humour eventually becomes separated from it as wit, jokes, and other comic forms, which then take on an independent life of their own.

These observations lead to the conclusion that humour evolves from androgen primed aggression.
So now you know. And how might you respond to the unexpected sight of a unicyclist?

Reference

Shuster S. (2007). Sex, aggression, and humour: responses to unicycling. BMJ 335:1320-1322.

Sunday, December 16, 2007

Truth may be beauty, and beauty truth,

in more than a metaphorical sense, and false propositions may actually disgust us (Harris et al., 2007).
When old age shall this generation waste,
Thou shalt remain, in midst of other woe
Than ours, a friend to man, to whom thou say'st,
"Beauty is truth, truth beauty," - that is all
Ye know on earth, and all ye need to know.

-- John Keats, Ode on a Grecian Urn

It's easy for the urn to say that, of course, because it doesn't have to bear the bruised ego caused by truthful remarks such as "that's a terrible hairstyle for you" or "wow, you look so poorly endowed in those Speedos" or the classic, "those jeans make you look fat!"

Blogging on Peer-Reviewed ResearchThe latest neuroimaging study in the Annals of Neurology (Harris et al., 2007) didn't really set out to prove Keats, but to determine
The difference between believing and disbelieving a proposition is one of the most potent regulators of human behavior and emotion. When one accepts a statement as true, it becomes the basis for further thought and action; rejected as false, it remains a string of words. The purpose of this study was to differentiate belief, disbelief, and uncertainty at the level of the brain.
The authors expected activation in the prefrontal cortex (PFC) to exert "top-down" control to bias behavior based on beliefs. Participants read statements designed to be clearly true, clearly false, or undecidable. These statements were from a number of different categories:

Mathematical: (2 + 6) + 8 = 16

Geographical: Wisconsin is on the West Coast of the United States.

Semantic: “Gigantic” means “huge.”

Factual: The Dow Jones Industrial Average rose 1.2% last Tuesday.

Autobiographical: You had eggs for breakfast on December 8, 1999.

Ethical: It is bad to take pleasure at another's suffering.

Religious: There is probably no actual Creator God.

That last one might be a bad example... how about "Jesus spoke 2,467 words in the New Testament" instead? Anyway, results from the True Statement minus False Statement contrast is shown bellow:

Figure 1A (from Harris et al., 2007). Ventromedial prefrontal cortex (VMPFC) regions showing positive blood oxygen level dependent (BOLD) signal for judgments of truth (belief) minus judgments of falsity (disbelief) across the seven stimulus categories.

Here we see activation in the VMPFC, which was the only area that showed greater activity for True versus False. HOWEVER, this was due to greater DEactivation during False Statements than during True Statements (when each was compared to an "implicit baseline" condition which wasn't described). The authors suggested that since this emotional processing area often shows decreases in BOLD signal during cognitive tasks, uh, hmmm... I'm not sure what they're getting at here:
The involvement of the VMPFC in belief processing suggests an anatomic link between the purely cognitive aspects of belief and emotion/reward. Even judging the truth and falsity of emotionally neutral propositions activated [NOTE: is less deactivation the same as activation?] brain regions that are strongly connected to the limbic system. It is not clear from these data whether emotional engagement enters directly into the assessment of propositional validity or whether it is a secondary consequence of the cognitive process, but the fact that ethical belief showed a similar pattern of activation to mathematical belief suggests that the physiological difference between belief and disbelief can be independent of a proposition's content and affective associations.
OK. What about the opposite contrast, False Statement minus True Statement?

Figure 2 (from Harris et al., 2007). Axial image shows increased BOLD signal in the inferior frontal gyrus (primarily the left), the right middle frontal gyrus, and the anterior insula (bilateral) when judgments of falsity (disbelief) are compared with judgments of truth (belief) across all stimulus categories. Sagittal image shows increased signal in the superior parietal lobule, the cingulate cortex, and superior frontal gyrus within the same contrast.

Not too surprisingly, the authors wanted to interpret the insula activation as a reflection of disgust at reading false statements. However, most of the false statements don't seem particularly disgusting:
Wisconsin is on the West Coast of the United States.
Devious means friendly.
Oh the horror. Additionally, they noted the similarity in frontal lobe activations for the False Statements here and "no" responses in prior studies of the Sternberg working memory task (e.g., saying "no" when the letter R was not in the study set of T J S Q). Honestly, can we really say anything about conventional notions of "belief" and "disbelief" from the Sternberg task? [I do not "believe" that R was in the study set]. Then we have the mystery activity:
...the rejection condition (disbelief) also showed increased signal in medial regions of superior parietal lobule, bilaterally. This is an area that has strong connectivity with the medial PFC, though its recruitment in the present task is not readily explained based on prior studies.
And what of uncertainty? Uncertainty was associated with greater activity in the anterior cingulate than either of the other two conditions. Also not surprisingly, the authors connected this result to response conflict, such as that observed in the Stroop effect. They concluded with a lovely philosophical discussion...
The human brain is a prolific generator of beliefs. Indeed, personhood is largely the result of the capacity of a brain to evaluate new statements of propositional truth in light of countless others that it already accepts. By recourse to intuitions of truth and falsity, logical necessity and contradiction, human beings are able to knit together private visions of the world that largely cohere. The results of our study suggest that belief, disbelief, and uncertainty are mediated primarily by regions in the medial PFC, the anterior insula, the superior parietal lobule, and the caudate. The acceptance and rejection of propositional truth-claims appear to be governed, in part, by the same regions that judge the pleasantness of tastes and odors.
...although it seems they are overstepping the bounds of their actual data.
He, who knows how to distinguish between true and false, must have an adequate idea of true and false.

-- Spinoza, from Ethics, Part II: On the Nature and Origin of the Mind

Reference

Harris S, Sheth SA, Cohen MS. (2007). Functional neuroimaging of belief, disbelief, and uncertainty. Ann Neurol. Dec 10; [Epub ahead of print].

OBJECTIVE: The difference between believing and disbelieving a proposition is one of the most potent regulators of human behavior and emotion. When one accepts a statement as true, it becomes the basis for further thought and action; rejected as false, it remains a string of words. The purpose of this study was to differentiate belief, disbelief, and uncertainty at the level of the brain. METHODS: We used functional magnetic resonance imaging (fMRI) to study the brains of 14 adults while they judged written statements to be "true" (belief), "false" (disbelief), or "undecidable" (uncertainty). To characterize belief, disbelief, and uncertainty in a content-independent manner, we included statements from a wide range of categories: autobiographical, mathematical, geographical, religious, ethical, semantic, and factual. RESULTS: The states of belief, disbelief, and uncertainty differentially activated distinct regions of the prefrontal and parietal cortices, as well as the basal ganglia. INTERPRETATION: Belief and disbelief differ from uncertainty in that both provide information that can subsequently inform behavior and emotion. The mechanism underlying this difference appears to involve the anterior cingulate cortex and the caudate. Although many areas of higher cognition are likely involved in assessing the truth-value of linguistic propositions, the final acceptance of a statement as "true" or its rejection as "false" appears to rely on more primitive, hedonic processing in the medial prefrontal cortex and the anterior insula. Truth may be beauty, and beauty truth, in more than a metaphorical sense, and false propositions may actually disgust us.

ADDENDUM #1: Until reading What Your Brain Looks Like on Faith (by David Van Biema), The Neurocritic did not know that the first author of the Harris et al. article is Sam Harris, the well-known nonfiction writer (The End of Faith and Letter to A Christian Nation) and highly-discussed atheist. [Oops!! He also happens to be a neuroscience graduate student at UCLA.]

ADDENDUM #2: Vaughan at Mind Hacks has posted The problem of believing in belief. He focuses on the philosophical definition of belief and whether the Harris et al. study really tells us anything about it:
...from what we know about belief it's not clear that this study tells us much more about belief rather than what happens when people respond to questions.
Yes. And deciding if the answer is Yes/No/Don't Know draws on different types of knowledge -- semantic memory, autobiographical memory, calculation -- which are heavily dependent on regions outside of PFC (e.g., temporal lobe, left inferior parietal cortex), and which do not have identical neural substrates. Although Harris would like to say there is no difference between beliefs about ethics and beliefs about mathematical equations, the experimental design is underpowered to detect such differences (which is why I didn't bother mentioning it in the first place).

Friday, December 14, 2007

Human or Alien?

To find out, now you too can take the latest Implicit Association Test (IAT)!

Human or Alien?


Mixing Memory has posted a hilarious summary of a satirical IAT paper, I See Dead People (Taking the Implicit Association Test). The paper bemoans the shocking decline in participants available to take the IAT. After describing the results of Study 1, the IAT in unborn babies,
...Bones and Johnson found another untapped population to study with the IAT: dead people. They point out that the work of people like M. Night Shyamalan has called into question the validity of people's self-report about whether they're alive or dead. An implicit measure of life or death is therefore important for both methodological and practical reasons.
For a good laugh, read the rest of the summary and the original paper by "Bones & Johnson" 2007.

Reference

Bones, A.K., & Johnson, N.R. (2007). Measuring the immeasurable: Or "Could Abraham Lincoln Take the Implicit Association Test?" Perspectives on Psychological Science, 2(4), 406-411.

With the Association for Psychological Science's new ethical standards requiring that all research studies include an Implicit Association Test (IAT), forecasters predict that the population of new participants available to take IATs will expire by the year 2023. Shrill, doomsday proposals from IAT experts involve rationing the precious pool of remaining IAT novices or other naive strategies. These solutions demonstrate rigid, scientific thinking, with a distinct lack of the creative flair that makes psychology stand apart from the real sciences. Building on our prior experience of adapting the IAT for measuring infant cognition and rooting out aliens among us, we demonstrate that new pools of participant resources—the unborn and passed on—are available, if we take the time to develop the methods to exploit them. Two studies illustrate some of the methodological challenges and opportunities that must be met in order to make better use of the new populations to keep the IAT juggernaut on its path of global (and interstellar) domination.

Monday, December 10, 2007

Human Rights Day


Human Rights Day 2007 marks the start of a year-long commemoration of the 60th anniversary of the Universal Declaration of Human Rights.
The Universal Declaration of Human Rights: 1948-2008

It is our duty to ensure that these rights are a living reality -- that they are known, understood and enjoyed by everyone, everywhere. It is often those who most need their human rights protected, who also need to be informed that the Declaration exists -- and that it exists for them.

-- Secretary-General Ban Ki-moon
It is especially hideous today to note the following article in the Washington Post:
[Four U.S. Congress Members] Briefed on Waterboarding in 2002

In Meetings, Spy Panels' Chiefs Did Not Protest, Officials Say

By Joby Warrick and Dan Eggen
Washington Post Staff Writers
Sunday, December 9, 2007


In September 2002, four members of Congress met in secret for a first look at a unique CIA program designed to wring vital information from reticent terrorism suspects in U.S. custody. For more than an hour, the bipartisan group, which included current House Speaker Nancy Pelosi (D-Calif.), was given a virtual tour of the CIA's overseas detention sites and the harsh techniques interrogators had devised to try to make their prisoners talk.

Among the techniques described, said two officials present, was waterboarding, a practice that years later would be condemned as torture by Democrats and some Republicans on Capitol Hill. But on that day, no objections were raised. Instead, at least two lawmakers in the room asked the CIA to push harder, two U.S. officials said.

. . .

With one known exception, no formal objections were raised by the lawmakers briefed about the harsh methods during the two years in which waterboarding was employed, from 2002 to 2003, said Democrats and Republicans with direct knowledge of the matter. The lawmakers who held oversight roles during the period included Pelosi and Rep. Jane Harman (D-Calif.) and Sens. Bob Graham (D-Fla.) and John D. Rockefeller IV (D-W.Va.), as well as Rep. Porter J. Goss (R-Fla.) and Sen. Pat Roberts (R-Kan).

Individual lawmakers' recollections of the early briefings varied dramatically, but officials present during the meetings described the reaction as mostly quiet acquiescence, if not outright support. "Among those being briefed, there was a pretty full understanding of what the CIA was doing," said Goss, who chaired the House intelligence committee from 1997 to 2004 and then served as CIA director from 2004 to 2006. "And the reaction in the room was not just approval, but encouragement."
However, in 2004, a quiet hero emerged from a most unlikely place -- from within the Bush Administration -- as described in this recent report by Amy Goodman:
In a remarkable demonstration of commitment to his job, former acting Assistant Attorney General Daniel Levin, according to ABC News, underwent waterboarding when tasked by the White House to rework its official position on torture in 2004. Concluding that waterboarding is torture, he was forced out of his job.
But here we have A Proclamation by the President of the United States of America:
Americans value deeply our ability to speak, assemble, and worship freely. As a Nation, we can help freedom-loving people everywhere build a world in which these rights are honored and respected. During Human Rights Day, Bill of Rights Day, and Human Rights Week, we celebrate the freedoms guaranteed to all Americans and protected in our Constitution's Bill of Rights.

. . .

NOW, THEREFORE, I , GEORGE W. BUSH, President of the United States of America, by virtue of the authority vested in me by the Constitution and laws of the United States, do hereby proclaim December 10, 2007, as Human Rights Day; December 15, 2007, as Bill of Rights Day; and the week beginning December 10, 2007, as Human Rights Week. I call upon the people of the United States to mark these observances with appropriate ceremonies and activities.
Oh the Hypocrisy of It All!

Friday, December 7, 2007

The Trouble With Bodies

You think you're yourself, but there are other persons in you.

In the funhouse mirror-room you can't see yourself go on forever, because no matter how you stand, your head gets in the way.


-- John Barth, Lost in the Funhouse
Individuals with body dysmorphic disorder (BDD) have a distorted body image that reaches criteria for a DSM IV psychiatric disorder. They are extremely critical of their physical appearance, despite the fact that there may be no noticeable disfigurement or defect.

Blogging on Peer-Reviewed ResearchA recent neuroimaging study examined possible neural correlates of this distorted self-image (Feusner et al., 2007). The participants were 12 people with BDD (10 women, 2 men1) and a set of well-matched controls. For this particular experiment, the focus was on faces, not bodies. The authors note that supposed defects in the face and head are among the most common preoccupations in BDD (Phillips, 2005).2

Drawing on neuropsychological evidence that these individuals are abnormally focused on details when copying and recalling the Rey-Osterrieth Complex Figure,3 along with the obvious propensity to perceive distortions in pictures of their own face, the authors manipulated the spatial frequency information contained in the face stimuli (through filtering, shown below). Participants viewed triplets of normal, LSF, or HSF face stimuli and performed a matching task.

Figure 1 (Feusner et al., 2007). Face stimuli. HSF indicates high spatial frequency; LSF, low spatial frequency; and NSF, normal spatial frequency. (On reproduction, the HSF image in this figure lost some of the detail that was visible in the experiment.)

Previous studies have shown that global "configural" information is contained in LSF, whereas local "featural" information, such as details about the eyes, nose, and mouth, is contained in HSF (e.g., Goffaux et al., 2005). In general, the right hemisphere is thought to be better at the former, and the left hemisphere at the latter. Were there differences between the BDD and control groups in the present study?
The BDD group demonstrated more left-sided activations in lateral aspects of the prefrontal and temporal cortices for all tasks, as well as dorsal anterior cingulate activity for the LSF task. The control group demonstrated this pattern only for the HSF task, suggesting that subjects with BDD use a similar network for processing NSH and LSF faces that control subjects use only for HSF faces. These laterality patterns suggest a bias for local, or detail, processing over global processing of faces for subjects with BDD. In addition, the BDD group showed abnormal activation of the amygdalae for HSF and LSF face tasks. We did not find differences in early ventral or dorsal visual stream regions as hypothesized; rather, the differences found are in regions that may represent later stages of visual processing or top-down effects.
Basically, for HSF stimuli, the BDD group had greater activation in the left middle and inferior temporal gyri than controls. More interestingly, for LSF stimuli, they showed greater activation in left-sided temporal-parietal regions and left inferior frontal gyrus than controls. This suggests the problem is with preferential attention to local aspects of faces, rather than an issue in the visual processing stream itself. In the future, it would be interesting to examine activation to the BDD subjects' own face, as well as other body parts perceived to be defective.


When you're lost, the smartest thing to do is stay put till you're found, hollering if necessary. But to holler guarantees humiliation as well as rescue; keeping silent permits some saving of face--you can act surprised at the fuss when your rescuers find you and swear you weren't lost, if they do. What's more you might find your own way yet, however belatedly.

-- John Barth, Lost in the Funhouse

Credits: Funhouse graphics and Barth quotes are from the website of the Florida Research Ensemble (Professor Gregory L. Ulmer et al.).


Footnotes

1 However, there may not be much of a gender discrepancy in the general BDD population, according to the Body Image Program at Butler Hospital in Rhode Island).

2 Dr. Katharine Phillips et al. have compiled a list of the most commonly disliked areas in a group of over 500 BDD patients.

3 Rey-Osterrieth Complex Figure.



References

Feusner JD, Townsend J, Bystritsky A, Bookheimer S (2007). Visual Information Processing of Faces in Body Dysmorphic Disorder. Arch Gen Psychiatry 64:1417-1425.

CONTEXT: Body dysmorphic disorder (BDD) is a severe psychiatric condition in which individuals are preoccupied with perceived appearance defects. Clinical observation suggests that patients with BDD focus on details of their appearance at the expense of configural elements. This study examines abnormalities in visual information processing in BDD that may underlie clinical symptoms. OBJECTIVE: To determine whether patients with BDD have abnormal patterns of brain activation when visually processing others' faces with high, low, or normal spatial frequency information. DESIGN: Case-control study. SETTING: University hospital. PARTICIPANTS: Twelve right-handed, medication-free subjects with BDD and 13 control subjects matched by age, sex, and educational achievement. Intervention Functional magnetic resonance imaging while performing matching tasks of face stimuli. Stimuli were neutral-expression photographs of others' faces that were unaltered, altered to include only high spatial frequency visual information, or altered to include only low spatial frequency visual information. Main Outcome Measure Blood oxygen level-dependent functional magnetic resonance imaging signal changes in the BDD and control groups during tasks with each stimulus type. RESULTS: Subjects with BDD showed greater left hemisphere activity relative to controls, particularly in lateral prefrontal cortex and lateral temporal lobe regions for all face tasks (and dorsal anterior cingulate activity for the low spatial frequency task). Controls recruited left-sided prefrontal and dorsal anterior cingulate activity only for the high spatial frequency task. CONCLUSIONS: Subjects with BDD demonstrate fundamental differences from controls in visually processing others' faces. The predominance of left-sided activity for low spatial frequency and normal faces suggests detail encoding and analysis rather than holistic processing, a pattern evident in controls only for high spatial frequency faces. These abnormalities may be associated with apparent perceptual distortions in patients with BDD. The fact that these findings occurred while subjects viewed others' faces suggests differences in visual processing beyond distortions of their own appearance.


Goffaux V, Hault B, Michel C, Vuong QC, Rossion B (2005). The respective role of low and high spatial frequencies in supporting configural and featural processing of faces. Perception 34:77-86.

Phillips KA. (2005). The Broken Mirror. New York, NY: Oxford University Press.

Self-portrait in a Broken Mirror, is that bad luck?
by Steve Smart
Creative Commons License

Thursday, December 6, 2007

This Is the Presidential Candidates' Brains On...

...an editorial in the Los Angeles Times. I guess the west coast paper felt left out of the New York Times op-ed brouhaha caused by This Is Your Brain on Politics (and the op-ed rejoinder by a group of experts -- Politics and the Brain).

From The Trouble With Oscillation, a project by artist Sally McKay.

Getting inside their heads ... really inside

Presidential candidates' health is a campaign issue. So what about their brains?

By Daniel G. Amen
December 5, 2007


What do Rudy Giuliani's messy personal life, John McCain's temper and Hillary Clinton's inability to seem authentic have in common? Maybe nothing. They may be just overblown issues in the otherwise normal lives of candidates under the political microscope.

Such symptoms, however, may mean a lot -- such as evidence of underlying brain dysfunction. Sometimes people with messy personal lives have low prefrontal cortex activity associated with poor judgment; sometimes people with temper problems have brain damage and impulse control problems; sometimes people who struggle with authenticity have trouble really seeing things from someone else's perspective.

Is the brain health of a presidential candidate a fair topic in an election year? Certainly Dick Cheney's heart condition wasn't off-limits in 2000... Should we go so far as to do brain scans? Of candidates for the Oval Office? Some people might consider discussing brain health a ridiculous idea. Not me.

As a neuropsychiatrist and brain-imaging expert, [NOTE: huh, 9 papers in mostly low-profile journals] I want our elected leaders to be some of the "brain healthiest people" in the land. How do you know about the brain health of a presidential candidate unless you look? ...

Three of the last four presidents have shown clear brain pathology. [NOTE: oh really?? we only have evidence for AD in Reagan, as much as we'd like to believe that George W. has brain damage.] President Reagan's Alzheimer's disease was evident during his second term in office. Nonelected people were covering up his forgetfulness and directing the country's business. Few people knew it, but we had a national crisis. Brain studies have been shown to predict Alzheimer's five to nine years before people have their first symptoms. [NOTE: uh...no. Published studies say 2-3 years.]

President Clinton's moral lapses and problems with bad judgment and excitement-seeking behavior -- indicative of problems in the prefrontal cortex -- eventually led to his impeachment and a poisonous political divisiveness in the U.S. The prefrontal cortex houses the brain's supervisor, involved with conscience, forethought, planning, attention span and judgment.

One could argue that our current president's struggles with language and emotional rigidity are symptoms of temporal lobe pathology. The temporal lobes, underneath your temples and behind your eyes, are involved with language, mood stability, reading social cues and emotional flexibility.
I seriously doubt that the "messy personal life" of Rudy Giuliani or Bill Clinton is evident from reading their SPECT scans (the imaging methodology used by Dr. Amen in his highly profitable clinics), or their ultra-high resolution 7T MRI scans, for that matter. However, Adrian Raine and colleagues at USC may want to take a look at Dick Cheney's brain...

In a future world with a high degree of diagnostic accuracy, perhaps
Ensuring that our president has a healthy brain may be more than an interesting topic of conversation. It can be important information to put into the election equation. A president with brain problems could wreak havoc on the U.S. and the world at large. Maybe we shouldn't leave the health of our president's brain to chance. We have the tools; shouldn't we look?
No! Not now. Not yet.

Wednesday, December 5, 2007

Sildenafil Improves Performance...

...cognitive performance, that is.

Sildenafil (aka Viagra) not only reduces jet lag in hamsters (Agostino et al., 2007), now it's been shown to improve object retrieval performance in monkeys (Rutten et al., 2007). Sildenafil is in the class of drugs known as phosphodiesterase inhibitors (PDEs). As indicated by the name, PDE drugs block phosphodiesterase, thereby preventing the degradation of cAMP and cGMP. Sildenafil inhibits the PDE5 subtype, whereas rolipram inhibits the PDE4 subtype.

Both drugs were equally effective in improving the monkeys' ability to correctly reach a food treat in a transparent box with one open side, which was billed as a prefrontal "executive function" task.
During vehicle sessions, monkeys readily reached for the food treats, successfully acquiring the treat on the first reach 100 ± 0% during easy trials and 52 ± 3% during difficult trials. Over the course of the experiment (2 months), there were no changes in vehicle performance.

The PDE4 inhibitor rolipram (0.003–0.1 mg/kg, i.m.) dose-dependently increased correct first reaches during difficult trials, reaching significance at 0.01 mg/kg. At the highest dose tested without side effects (0.03 mg/kg), the percentage correct first reaches were increased approximately 20 to 71 ± 3%.

The PDE5 inhibitor sildenafil (0.3–3 mg/kg, i.m.) dose-dependently increased correct first reaches during difficult trials, reaching significance at 1 mg/kg. At the highest dose tested (3 mg/kg), correct reaches were increased approximately 20 to 73 ± 3%. No side effects were observed.

Neither rolipram nor sildenafil altered performance during the easy trials, with the exception of the high dose of rolipram (0.1 mg/kg), in which monkeys failed to perform the task (data not shown) because of emetic side effects.


The mechanism(s) by which these PDE drugs might improve functioning of the prefrontal cortex are not well-elucidated at this point.

References

Agostino PV, Plano SA, Golombek DA. (2007). Sildenafil accelerates reentrainment of circadian rhythms after advancing light schedules. PNAS 104: 9834–9839.

Rutten K, Basile JL, Prickaerts J, Blokland A, Vivian JA. (2007).
Selective PDE inhibitors rolipram and sildenafil improve object retrieval performance in adult cynomolgus macaques. Psychopharmacology, Nov 23; [Epub ahead of print].

Sunday, December 2, 2007

Mirror Neurons in Primary Motor Cortex?


The mirror neurons, it would seem, dissolve the barrier between self and others. I call them "empathy neurons" or "Dalai Llama neurons".

-- MIRROR NEURONS AND THE BRAIN IN THE VAT
by V.S. Ramachandran

Everyone knows what mirror neurons are, those darlings of the pop neuroscience world. First observed in the ventral premotor area F5 of macaque monkeys, mirror neurons increase their rate of firing when the animal performs an action, and when the animal watches someone else perform the action (Rizzolati et al, 1996). These "monkey see, monkey do" neurons have taken on a life far beyond their originally postulated role in imitation. However, not everyone believes that mirror neurons can account for all aspects of human language, culture, and social cognition -- from empathy to altruism to autism to aesthetics to
certain listeners' misattribution of anger in the music of avant garde jazz saxophonists (Gridley & Hoff, 2006)
-- as explained by Alison Gopnik [see also The Neurocritic, Mixing Memory, Neurofuture, et al.]:
The idea that these particular cells might underlie a fundamental human impulse [altruism] reflects the emergence of a new scientific myth. Like a traditional myth, it captures intuitions about the human condition through vivid metaphors.
Blogging on Peer-Reviewed ResearchAn intriguing new study in the Journal of Neuroscience (Tkach et al., 2007) describes neuronal activity in the primary motor cortex (MI, also called M1) and dorsal premotor cortex of monkeys that looks an awful lot like that of mirror neurons, heretofore confined to ventral premotor cortex and the inferior parietal lobe. The authors conclude that
congruence between observation and action is a general feature of the motor system, even outside of canonical "mirror" areas.
Why is this so interesting? Primarily because of what's going on in M1. If [some] cells there show similar activity during both the execution and observation of actions, what's preventing the arm from moving in the latter case?
If our interpretation of this phenomenon is correct and the monkeys are generating covert motor commands during observation that are congruent with the commands generated during the behavior itself, a natural question is how the dissociation between motor cortical modulation and action occurs. One possibility is that the motor cortical activity we observe is being actively gated by other cortical areas. Results from human EEG studies along with our LFP results suggest that an increase in power in the beta range is associated with inhibition of the excitatory state of the motor cortex (Gilbertson et al., 2005). There is some clinical evidence regarding the origin of this inhibition in patients with frontal lobe damage that exhibit "unwilled" automatic movements (Archibald et al., 2001). These clinical studies suggest that the prefrontal, anterior cingulate, and supplementary motor cortices may contribute the necessary inhibition to prevent triggering of movement commands realized in activated motor and premotor cortical areas. Another possibility is that the motor cortex is part of a more distributed network responsible for movement. Therefore, motor cortical activity alone may not be sufficient to elicit action. Without knowing more about the functional roles of the cells from which we are recording, it is difficult to say anything further about the mechanisms intervening between stimulus and response during the observation phase of the experiment.
In the end, we return to the question, "What's so special about mirror neurons?" We know virtually nothing about the morphological properties of these magical cells (unlike their media cousins, the spindle neurons), so the answer awaits another day (and results from some highly impractical experiments).

References

Gridley MC, Hoff R. (2006). Do mirror neurons explain misattribution of emotions in music? Percept Mot Skills 102:600-2.

Rizzolatti G, Fadiga L, Gallese V, Fogassi L. (1996). Premotor cortex and the recognition of motor actions. Cog Brain Res. 3:131-41.

Tkach D, Reimer J, Hatsopoulos NG. (2007). Congruent activity during action and action observation in motor cortex. J Neurosci. 27:13241-50.

A variety of studies have shown that motor cortical areas can be activated by observation of familiar actions. Here, we describe single-neuron responses in monkey primary motor (MI) and dorsal premotor (PMd) cortices during passive observation and execution of a familiar task. We show that the spiking modulation, preferred directions, and encoded information of cells in MI and PMd remain consistent during both observation and movement. Furthermore, we find that the presence of a visual target is necessary to elicit this congruent neural activity during observation. These findings along with results from our analysis of the oscillatory power in the beta frequency of the local field potential are consistent with previous imaging and EEG studies that have suggested that congruence between observation and action is a general feature of the motor system, even outside of canonical "mirror" areas. Such congruent activity has proposed relevance to motor learning, mimicry, and communication and has practical applications for the development of motor-cortical neuroprostheses in paralyzed patients.

Saturday, December 1, 2007

D1 Receptor Knock-Out Mice Say, "No Cocaine for Us!"

"However, we'll still take plenty of food and opioid agonists!"

Unlike mice with the dopamine D2 receptor "knocked out," D1 receptor-deficient mice will no longer self-administer cocaine:
Caine SB, Thomsen M, Gabriel KI, Berkowitz JS, Gold LH, Koob GF, Tonegawa S, Zhang J, Xu M. (2007). Lack of Self-Administration of Cocaine in Dopamine D1 Receptor Knock-Out Mice. J. Neurosci. 27:13140-13150.

Evidence suggests a critical role for dopamine in the reinforcing effects of cocaine in rats and primates. However, self-administration has been less often studied in the mouse species, and, to date, "knock-out" of individual dopamine-related genes in mice has not been reported to reduce the reinforcing effects of cocaine. We studied the dopamine D1 receptor and cocaine self-administration in mice using a combination of gene-targeted mutation and pharmacological tools. Two cohorts with varied breeding and experimental histories were tested, and, in both cohorts, there was a significant decrease in the number of D1 receptor knock-out mice that met criteria for acquisition of cocaine self-administration (2 of 23) relative to wild-type mice (27 of 32). After extinction of responding with saline self-administration, dose–response studies showed that cocaine reliably and dose dependently maintained responding greater than saline in all wild-type mice but in none of the D1 receptor knock-out mice. The D1-like agonist SKF 82958 (2,3,4,5,-tetrahydro-6-chloro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrobromide) and the D2-like agonist quinelorane both functioned as positive reinforcers in wild-type mice but not in D1 receptor mutant mice, whereas food and intravenous injections of the opioid agonist remifentanil functioned as positive reinforcers in both genotypes. Finally, pretreatment with the D1-like antagonist SCH 23390 [R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-01] produced surmountable antagonism of the reinforcing effects of cocaine in the commonly used strain C57BL/6J. We conclude that D1 receptor knock-out mice do not reliably self-administer cocaine and that the D1 receptor is critical for the reinforcing effects of cocaine and other dopamine agonists, but not food or opioids, in mice.

Friday, November 23, 2007

Employment Opportunity as a Professional fMRI Subject

Blogging on Peer-Reviewed ResearchApply now!

Or at least, that's the implication of this BBC story about the latest neuroimaging paper (Fliessbach et al., 2007) in Science:
Men motivated by 'superior wage'
[NOTE: so I guess women aren't, eh?
we don't know, since they weren't tested
]


Brain scans show we measure our success by others' earnings

On receiving a paypacket, how good a man feels depends on how much his colleague earns in comparison, scientists say.

Scans reveal that being paid more than a co-worker stimulates the "reward centre" in the male brain.
What was the study actually about?
The absolute consumption level, or alternatively the absolute level of income, is the most important determinant of individual well-being in traditional economic models of decision-making. These models typically assume that social comparisons, and therefore relative income, play no role. This view has long been challenged by social psychologists and anthropologists, who have argued that comparison with other individuals is a central phenomenon within human societies...
OK, so we already know that social comparisons and relative income matter. What can we learn from this study? Is it much of a surprise that the participants were competitive?
Despite the importance of distinguishing the roles of absolute and relative income levels for subjective well-being, and thus for human decision-making, the underlying neurobiological basis of social comparison is not well understood.
Yeah, OK, stick people in a scanner and see what happens. What did the professional subjects do while there? Pairs of participants were scanned simultaneously in two different magnets while estimating the number of dots presented on a computer screen. After each trial, both participants received feedback on how each of them had done, and how much money was earned according to a predefined payment schedule. So what happened?
...conditions in which a subject solved the task correctly and received a payment while the other subject did not were contrasted with conditions in which a subject received no payment. This contrast yielded significant activation in three bilateral and three medial regions, which defined our regions of interest: left and right occipital cortex, left and right angular gyrus, left and right ventral striatum [see above figure], precuneus, and medial orbitofrontal cortex (two distinct activations), thus including the regions known to be critically involved in the processing of reward.
So all these other brain regions were activated as well. Why occipital cortex and angular gyrus? We'll never know, because the authors never discuss the significance of those responses. What was so distinctive about the ventral striatum, then?
According to our hypothesis, the parameter estimates increased with the ratio between a subject's reward and the other subject's reward... All other main effects and interactions of the ANOVA analysis turn out to be insignificant. This holds for the main effect of high versus low payment condition as well as its interaction with relative payment. The latter result suggests that the importance of relative comparison is independent of the level of payment. ... All posterior regions (occipital lobe, angular gyrus, and precuneus/cingulate cortex) showed a different pattern, with response intensity significantly varying with both absolute and relative payment. In these regions, responses were highest ... in situations when high amounts of money were unequally paid regardless of which of the subjects received more. A similar pattern was found in the two orbitofrontal regions.
In brief, the ventral striatum was uniquely related to greater relative reward (not just absolute reward). So what have we learned? It's rewarding to win a competition and to earn more money than a rival.

Reference

K. Fliessbach, B. Weber, P. Trautner, T. Dohmen, U. Sunde, C. E. Elger, A. Falk (2007). Social Comparison Affects Reward-Related Brain Activity in the Human Ventral Striatum. Science 318:1305-1308.

Whether social comparison affects individual well-being is of central importance for understanding behavior in any social environment. Traditional economic theories focus on the role of absolute rewards, whereas behavioral evidence suggests that social comparisons influence well-being and decisions. We investigated the impact of social comparisons on reward-related brain activity using functional magnetic resonance imaging (fMRI). While being scanned in two adjacent MRI scanners, pairs of subjects had to simultaneously perform a simple estimation task that entailed monetary rewards for correct answers. We show that a variation in the comparison subject's payment affects blood oxygenation level–dependent responses in the ventral striatum. Our results provide neurophysiological evidence for the importance of social comparison on reward processing in the human brain.

Wednesday, November 21, 2007

High IMPACT Exercise


Initial results from The IMPACT Study (Improvement in Memory with Plasticity-based Adaptive Cognitive Training) were presented at a recent conference, as touted in this press release:
New Research on Aging and Cognitive Training

Researchers released initial data today at the 60th Annual Meeting of The Gerontological Society of America (GSA) that showed that doing the right kind of brain exercise can enhance memory and other cognitive abilities of older adults.

Dr. Elizabeth Zelinski of the University of Southern California Andrus Gerontology Center presented data from the IMPACT study (Improvement in Memory with Plasticity-based Adaptive Cognitive Training) – the largest study ever done on aging and cognitive training using a program available to the public. In this prospective, randomized, controlled, double blind trial of 524 healthy adults (aged 65 and older), half the participants completed up to 40 hours of the computer-based Posit Science Brain Fitness Program. The other half, who followed the traditional advice that older adults will benefit from new learning, completed up to 40 hours of a computer-based educational training program.

The group that engaged in the Posit Science program showed significantly superior improvements in standardized clinical measures of memory gains of approximately 10 years. This is the first research study to show generalization to untrained standardized measures of memory using a publicly available cognitive training program. ...

In brief, 10 weeks of the training program, which targeted the speed/accuracy of auditory and language processes, resulted in improvements in auditory memory in a large group of intelligent, well-educated, highly-functioning elderly adults (when compared to an "active control" group). The conference poster is available for download, The IMPACT Study: A Randomized Controlled Trial of a Brain Plasticity-Based Training Program for Age-Related Cognitive Decline.

Next up: combining the auditory memory benefits of computerized cognitive training with the executive control benefits of aerobic fitness training. Has Posit approached Art Kramer yet?