Sunday, April 30, 2006

Quotidian Virtual Violence

The title of this article (below) and its abstract certainly caught my eye (they actually did use the word "quotidian" and did state that playing violent video games is a natural, real-life behavior).

Human Brain Mapping
Early View (Articles online in advance of print)
Published Online: 20 Apr 2006

Toward brain correlates of natural behavior: fMRI during violent video games
Klaus Mathiak, Rene Weber

Modern video games represent highly advanced virtual reality simulations and often contain virtual violence. In a significant amount of young males, playing video games is a quotidian activity, making it an almost natural behavior. Recordings of brain activation with functional magnetic resonance imaging (fMRI) during gameplay may reflect neuronal correlates of real-life behavior. We recorded 13 experienced gamers (18-26 years; average 14 hrs/week playing) while playing a violent first-person shooter game (a violent computer game played in self-perspective) by means of distortion and dephasing reduced fMRI (3 T; single-shot triple-echo echo-planar imaging [EPI]). Content analysis of the video and sound with 100 ms time resolution achieved relevant behavioral variables. These variables explained significant signal variance across large distributed networks. Occurrence of violent scenes revealed significant neuronal correlates in an event-related design. Activation of dorsal and deactivation of rostral anterior cingulate and amygdala characterized the mid-frontal pattern related to virtual violence. Statistics and effect sizes can be considered large at these areas. Optimized imaging strategies allowed for single-subject and for single-trial analysis with good image quality at basal brain structures. We propose that virtual environments can be used to study neuronal processes involved in semi-naturalistic behavior as determined by content analysis. Importantly, the activation pattern reflects brain-environment interactions rather than stimulus responses as observed in classical experimental designs. We relate our findings to the general discussion on social effects of playing first-person shooter games.

Funded by:
TL Foundation
Deutsche Forschungsgemeinschaft (DFG); Grant Number: SFB550/B1, Th812/1-1
U.S. Annenberg Endowment

There are a lot of tricky technical issues involved in recording fMRI under these conditions, but the authors discussed them (e.g., experimenters can't control the time course of stimuli and responses in an interactive game) and developed analytic procedures to deal with these challenges.

"The present study introduces a procedure to describe interactive behavior as observed during playing a first-person shooter video game in a parametric design.

Content analysis of text and audiovisual stimuli is frequently applied in media research and can be considered a reliable and valid method [Krippendorf, 1980]. Content analysis of video game playing can capture individual interaction patterns within the virtual environment, including violent interactions [Weber et al., 2006]. First-person shooter games are controversially discussed media products but certainly reflect state-of-the-art VR. Taken together, first-person shooter games represent a challenging paradigm for interdisciplinary research of media psychology, communication sciences, and social cognitive neuroscience. The present fMRI study investigated neuronal activity during complex virtual behavior as represented by playing a first-person shooter game with respect to meaningful categories such as violence."

It appears that our old friends the amygdala and the anterior cingulate cortex are involved in virtual violence (but then, the authors focused on these structures a priori). The amygdala and rostral ACC (aka "sad cingulate") showed decreases in activity, and the dorsal ACC (1) showed increases in activity, while the 23 year old German male gamers were engaged in "violent interactions" (relative to "passive/dead" and "preparation/search" states, where there were no violent interactions). The authors' interpretation?

"This pattern suggested active suppression of affective processing in favor of the cognitive operation."

You need use cool rational cognition when shooting at the enemy in "Tactical Ops: Assault on Terror." The media should have a field day with this, but the article isn't in Science or Nature, so we'll see how far it goes without a press release (and with qualifying statements like this one):

One might speculate that a frequent training of aggressive neuronal pattern leads to the development of aggressive problem-solving scripts, hostile attribution biases, and normative beliefs approving of aggression as stated by social-cognitive theory [Bandura, 2001]. This proposition with its important implications, however, is not a direct conclusion of this study's findings.

(1) but note that dorsal ACC is also active during empathy for pain, so perhaps the gamers secretly felt sorry for their prey...

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Saturday, April 29, 2006

Shame on the Society for Neuroscience!

I was reading an article about Jazzfest in New Orleans when I got all riled up again about SFN's decision to move the annual meeting from NOLA to Atlanta in 2006 (perhaps understandable) AND to Chicago in 2009 (a cheap and tawdry decision).

Festgoers put the city's pain and loss on the back burner to enjoy the sweet sounds of Jazzfest
Saturday, April 29, 2006
By Gwen Filosa

At the first New Orleans Jazz and Heritage Festival since Hurricane Katrina blanketed the city with sorrow and pain, colorful flags flew. They flew beneath a sweet late-spring breezes and sunshine. They flew in spite of the recent memories of loss and the continuing difficulties.

Opening-day attendance was huge, uniting the tattooed, the shirtless, the braless and all those who adore New Orleans.

"We knew we had to be here opening day," said Rod Frable, 54, who came from Tucson, Ariz., with Barry Jacoby, 63, to mark yet another Jazzfest. "This is the time to be here. The music is going to be greater than ever. These people are coming down here to revitalize the city."

Unfortunately, 25,000 neuroscientists will not be revitalizing the city any time in the foreseeable future. SFN seems to have removed any trace of their decision (and the ensuing debate) from their web site. I've been a member of the society since, oh, 19xx (i.e., for a long time), but my voice (and those of many many pro-NOLA members) did not matter.

Shame on you, SFN!!

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Belgian Study Touts Open Access Publishing for EU

Elsevier is bad, says 112 page report.

Brussels delivers blow to Reed Elsevier

· Pricing of journal papers 'impedes science progress'
· Internet access proposal puts lucrative trade at risk

Richard Wray
Wednesday April 19, 2006
The Guardian

Scientific research funded by the European taxpayer should be freely available to everyone over the internet, according to a European commission report - a blow to the lucrative scientific publishing operations of media groups such as Reed Elsevier and Germany's Springer.

The report, produced by economists from Toulouse University and the Free University of Brussels for the EC, shows that in the 20 years to 1995 the price of scientific journals rose 300% more than the rate of inflation over the period. In the 10 years since then, price increases slowed but still significantly outpaced inflation.

"While it is important to stress the societal value of the existing publication system, it is also important to acknowledge the societal cost linked to high journal prices, in financial terms for public budgets, but also in terms of limits on the dissemination of knowledge and therefore of further scientific progress," the report concludes.

The report, published this month and open to consultation until the summer, recommends open access to publicly funded research. It proposes that researchers who receive EU funding should be "mandated" to place copies of articles published in subscription journals on web-based archives that can be accessed by everyone for free.

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Sex Cues Ruin Men's Decisiveness

...or so says the headline at Cosmopolitan, er uh BBC News.

Brief summary below from Vaughan at Mind Hacks.brown_bikini_girl.jpg

Lingerie sharpens the financial mind

According to recent news reports, the sight of lingerie or a sexy woman significantly impairs male decision making. Unfortunately, the details have got a little blurred in the re-telling from the original research paper - to the point where most reports flatly contradict the study's conclusions.

. . .

The best write-up of the study's details I've found is from Nature, who do the study justice and point out that the results actually contradict the idea that sexy images makes men less rational. In the study, they actually made men more rational.


And some great observations on all the hoopla from Dr Petra (sex and relationship psychologist):
A glimpse of panties and men can’t function

If I were to say to you men can’t be trusted in positions of power because they think with their dicks, you’d tell me I was being unfair.

Sure, there are stereotypes of men are preoccupied with sex, but to claim sex gets in the way of men’s abilities to manage even simple tasks suggests men are just brainless Neanderthals.

Yet in many of today’s papers that’s exactly the message being given. It’s based on research from a Belgian University that’s found men are so distracted by sexy women they can’t even focus on a simple lab task.

Instead of challenging the many flaws and assumptions behind the research, science writers and other reporters have run with a ‘this confirms what we’ve always known about men’ approach. It’s amazing in a media that’s increasingly quick to see men as the underdogs when it comes to a study that’s doing men down nobody seems to notice. In fact most journalists have been happy to perpetuate sexist stereotypes.

. . .

We often think of women as hormonally driven, but this research is doing the same thing for men. It’s arguing that given enough testosterone you’re irrational and impulsive. In other research we’re constantly told how men in powerful positions are often more likely to have higher testosterone levels. So if we’re to believe this research it’s really telling us is powerful men can’t be trusted to make any sensible decisions because you only need a petticoat to enter the room and men’ll be foaming at the mouth, forgetting all the important stuff.

If this is the case we’ve a great answer to ending all our wars or political problems. Simply get a ‘sexy woman’ to sashay through a board meeting and peace will be restored.

—Dr Petra

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Monday, April 24, 2006

Neurofeedback in Autism

After complaining bitterly about a bad article in last week, today I'm happy to post a link to another New Scientist story, which discusses a line of very worthwhile research on "brain training" in autism:
Brain training can change autistic behaviour

NEUROFEEDBACK practice may be able to alleviate some of the symptoms of autism, according to a pilot study on eight children with the disorder.

The technique involves hooking people up to electrodes and getting them to try and control their brain waves. In people with autism, the "mu" wave is thought to be dysfunctional. Since this wave is associated with "mirror neurons" - the brain cells that underpin empathy and understanding of others - Jaime Pineda at the University of California, San Diego, wondered if controlling it through neurofeedback could exercise faulty mirror neurons and improve their function.

He attached sensors to the necks and heads of eight children with autism and had them watch a video game of a racing car going round a track. For all of the children, sitting still and concentrating kept the car travelling around the track, but five of them were also able to harness their mu waves and use them to adjust the car's speed.

After 30 sessions over 10 weeks, Pineda found that the five children's mu brainwaves had changed and they performed better on tasks involving imitation, typically difficult for people with autism. Pineda presented his work at the annual meeting of the Cognitive Neuroscience Society in San Francisco last week.

"This seems to indicate the children improve," Pineda says. How long the effects will last, though, is unknown.

From issue 2548 of New Scientist magazine, 21 April 2006, page 17
Although preliminary, the work of Jaime Pineda and his colleagues is a promising application of heretofore trendoid basic science research on "mirror neurons". It makes use of the mu wave in the EEG. Their work has shown that:
suppression of EEG oscillations in the mu frequency (8-13Hz) band over prefrontal cortex is correlated with mirror neuron activity. [They] study this mu wave suppression in a variety of populations to determine how a dysfunctional mirror neuron system may contribute to the pathology in autism, addiction, and other disorders, including a lack of theory of mind.
Venture capitalists!! Why aren't you more forthcoming with financial support for research like that (and research on brain-computer interfaces (BCIs) that allow paralyzed individuals to communicate)?? Why are you supporting only neuromarketing research on "mirror neurons"? Oh never mind, we already know the answer to that question.

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Thursday, April 20, 2006

Lose Yourself

You better lose yourself in the music, the moment
You own it, you better never let it go
You only get one shot, do not miss your chance to blow
This opportunity comes once in a lifetime yo

--Eminem, Lose Yourself

When the Brain Loses Its Self: Prefrontal Inactivation during Sensorimotor Processing
Ilan I. Goldberg, Michal Harel, and Rafael Malach
Neuron, Vol 50, 329-339, 20 April 2006

A common theme in theories of subjective awareness poses a self-related “observer” function, or a homunculus, as a critical element without which awareness can not emerge. Here, we examined this question using fMRI. In our study, we compared brain activity patterns produced by a demanding sensory categorization paradigm to those engaged during self-reflective introspection, using similar sensory stimuli. Our results show a complete segregation between the two patterns of activity. Furthermore, regions that showed enhanced activity during introspection underwent a robust inhibition during the demanding perceptual task. The results support the notion that self-related processes are not necessarily engaged during sensory perception and can be actually suppressed.
Let's say you're interested in the "neural correlates of consciousness", specifically that peculiar variant sometimes known as self-awareness. When contemplating the nature of your own self-awareness, it seems obvious that you are not focused on your existence as a unique entity, a human being with a "unitary" sense of self, 24 hours a day, or even during sober non-drug-addled waking hours. It would be a surprising, in fact, if the brain regions most active during self-reflective introspection were the exact same ones most active while you're engaged in a demanding perceptual task. You don't have the cognitive resources available to do both at the same time (at least, to do both very well at the same time). And it seems readily apparent that when you're daydreaming or introspecting, you're less aware of your physical surroundings.

Nevertheless, the paper by Goldberg et al. comes to this obvious conclusion: there was "a complete segregation between the two patterns of activity" [self-reflective introspection vs. demanding perceptual task].

Now what does this mean? According to the authors,
Our results show a clear segregation between regions engaged during self-related introspective processes and cortical regions involved in sensorimotor processing. Furthermore, self-related regions were inhibited during sensorimotor processing. Thus, the common idiom ‘‘losing yourself in the act’’ receives here a clear neurophysiological underpinnings. [sic... oh copy editor!?!]
What did they actually show in their experiment? The task conditions were as follows:
  1. Categorization/Slow - view pictures or listen to short musical clips presented once every 3 seconds. Classify the pictures as animal/non-animal and the tunes as trumpet/non-trumpet.
  2. Categorization/Fast - same as above, but stimuli presented once every second.
  3. Introspection/Slow - same stimuli presented at the slow rate, but think about your emotional reaction to each one and rate it as high or low.
Oh, they didn't have an Introspection/Fast condition?? But maybe you'd be less "self-aware" if you had to react to the stimuli more quickly...

ANYWAY, in the Categorization/Slow versus Introspection/Slow comparison,
Regions selectively activated by the introspection task were found within the superior frontal gyrus (SFG) extending medially to the anterior cingulate region and caudally to the paracingulate region; the latter region showed similar activation also in the right hemisphere. Additional focus was found in the posterior part of the middle frontal gyrus, just anterior to the precentral sulcus. Finally, bilateral activations were found in the posterior part of the inferior frontal gyrus extending to the anterior insula. ... No cortical region showed the opposite preference, i.e., significantly higher activations to slow categorization versus introspection.
So a pretty wide swath of superior and medial frontal cortex was activated to a greater extent in the introspection task, but presumably similar (other) regions were engaged by both tasks. As predicted, the Categorization/Fast condition engaged sensorimotor cortex to a greater extent than the Categorization/Slow condition.

I guess the key finding here is that SFG and other introspective frontal regions were deactivated (i.e., below resting baseline levels) in the categorization conditions, and this is the supposed neurophysiological underpinning of "losing yourself."

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I'm Super! The "Superfrontal Gyrus" is the Seat of Self-Awareness!

The New Scientist has a horrible article on a new fMRI study :
Watching the brain 'switch off' self-awareness
. . .

The team conducted a series of experiments to pinpoint the brain activity associated with introspection and that linked to sensory function. They found that the brain assumes a robotic functionality when it has to concentrate all its efforts on a difficult, timed task – only becoming "human" again when it has the luxury of time.

. . .

Goldberg found that when the sensory stimulus was shown slowly, and when a personal emotional response was required, the volunteers showed activity in the superfrontal gyrus – the brain region associated with self-awareness-related function.

But when the card flipping and musical sequences were rapid, there was no activity in the superfrontal gyrus, despite activity in the sensory cortex and related structures.

. . .
Seriously, the "superfrontal" gyrus does not exist, perhaps writer Gaia Vince meant "superior frontal gyrus." And I doubt that the subjects turned into robots when the card flipping and musical sequences were rapid. I'll read the original paper in Neuron and report back.

This is definitely one for BAD Neuro-Journalism!

Thanks to Elliot for the link.

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Monday, April 17, 2006

The Sad Cingulate Before CBT

The latest sad cingulate news is an fMRI study that examined the responsiveness of this region (subgenual cingulate cortex, aka Brodmann area 25) to emotional stimuli as a predictor of recovery in depressed patients receiving cognitive behavior therapy (CBT).

Fourteen depressed individuals were scanned while they rated the personal relevance of words that were positive, negative, or neutral. Then the subjects received 16 sessions of CBT over a 12 week period. To detect brain regions that were associated with recovery, the authors (Siegle et al.) ran whole-brain voxelwise analyses to find regions that correlated with
changes in symptom severity after therapy. Lo and behold, the only brain area that was associated with improvement was BA 25.

In the graph above, I've drawn in dotted red lines to illustrate the participants who did show a treatment response. These 7 people (in the lower left-hand corner of the graph) got better after CBT (change in Beck Depression Inventory score is negative) AND showed a decrease in BA 25 activity after viewing negative words ("sustained" BA 25 signal is also negative). The graph is correct in predicting the outcome of 11 out 14 patients (78.6%).

OK, what kind of neural responsiveness are we really looking at here? The "sad cingulate" hemodynamic response was measured in an interval 6-10 sec after subjects rated the self-relevance of a negative word, compared to a pre-stimulus baseline. SO the subgenual cingulate was more active in the baseline "resting" state than in the "rate words" condition. This would be consistent with the elevated "resting state" activity in BA 25 seen by Mayberg et al., which reverted to control levels in those who responded to SSRIs.

In the current study, we don't know what happened to neural activity in BA 25 after the full course of CBT. Furthermore, the task-related decrease in BA 25 activity was not specific to negative words... it also occurred to positive and neutral words in the CBT responders, so I'm not sure why the authors claim that the responders showed deficient emotional control processes (since the same pattern of neural responsiveness was obtained to neutral words).
Use of fMRI to Predict Recovery From Unipolar Depression With Cognitive Behavior Therapy.
Greg J. Siegle, Ph.D., Cameron S. Carter, M.D. and Michael E. Thase, M.D.
American Journal of Psychiatry 163:735-738, April 2006

OBJECTIVE: In controlled treatment trials, 40%–60% of unmedicated depressed individuals respond to cognitive behavior therapy (CBT). The authors examined whether pretreatment neural reactivity to emotional stimuli accounted for this variation. METHOD: Unmedicated depressed individuals (N=14) and never depressed comparison subjects (N=21) underwent fMRI during performance of a task sensitive to sustained emotional information processing. Afterward, depressed participants completed 16 sessions of CBT. RESULTS: Participants whose sustained reactivity to emotional stimuli was low in the subgenual cingulate cortex (Brodmann’s area 25) and high in the amygdala displayed the strongest improvement with CBT. CONCLUSIONS: The presence of emotion regulation disruptions, which are targeted in CBT, may be the key to recovery with this intervention.
SUMMARY from The Neurocritic: the authors' interpretation of the BA 25 results seemed a little convoluted to me. Perhaps more noteworthy (or at least straightforward) is what happened in the amygdala (using a region of interest analysis): it showed a huge response to negative words in the depressed people but not the controls. This is nothing new, but the huge and specific amygdala response to negative words was larger in CBT responders than non-responders, and it correlated with self-report on a rumination scale.

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Saturday, April 15, 2006

I Just Can't Get Enough, I Just Can't Get It Up

No, this entry is not an announcement that David Gahan uses Viagra, but a pointer to a series of articles in PLoS Medicine on the phenomenon of "disease mongering." Some of the diseases mongered include ADHD, bipolar disorder, erectile dysfunction, and the particularly slippery diagnosis of female sexual dysfunction. Of course, many many people are legitimately diagnosed with these disorders and helped immensely by pharmaceutical treatments. However, advertising campaigns designed to expand the diagnostic categories broadly covered by a particular drug are the insidious new trend criticized by the PLoS Medicine authors.

In the words of Dr Petra (sex and relationship psychologist):
"If we take sexual functioning as an example, the pharmaceutical industry want us to see not having sex as a disease, since they’re working to find ‘cures’. They want their sex medications to be seen as lifestyle enhancers, and they want us to feel the need to take sex meds to boost our desire, increase our arousal, and improve our capacity for orgasm and sexual functioning. They use the media to whet our appetites with teaser stories about forthcoming sex products and to constantly remind us how we ought to be sexually functioning (so that when we don’t measure up we feel the need to reach for a cure). Many journalists I’ve spoken to interpret these stories as exciting new scientific breakthroughs -- they don’t even know often that they’re being spun a line.

The media has been at the forefront of promoting erectile enhancing drugs, clamouring for drugs to ‘cure’ premature ejaculation, female sexual dysfunction, and testosterone supplements for both sexes.

Until the media take a critical stance on the PR stories they’re sent from pharmaceutical companies (or academic departments funded by pharmaceutical companies) we’ll continue to have them offering free advertising to Big Pharma."

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Thursday, April 13, 2006

Dopa-mine and You, Dopa-mine and Me. . .

...always have a lot of fun together!

There was a symposium entitled "Dopaminergic Modulation of the Adaptive Mind" at the recent Cognitive Neuroscience meeting. Although behavioral pharmacologists have studied the effects of dopaminergic (and noradrenergic and serotonergic) drugs in animals for years, only recently has a similar (albeit much less invasive) approach come into vogue in studies of human cognition. Part of this new-found trendiness comes from functional neuroimaging -- give a person a drug (versus placebo), see what activation changes occur in the brain when the subject is doing XYZ (or CPT-AX) task. However, many neuroscientists (such as Robert Oades) have been interested in these questions for over 20 years, but their work has been mostly neglected by cognitive types:
Oades RD (1985). The role of noradrenaline in tuning and dopamine in switching between signals in the CNS. Neurosci Biobehav Rev. 9(2):261-82.

Neuronal catecholaminergic activity modulates central nervous function. Specifically noradrenaline can exert a tuning or biassing function whereby the signal to noise ratio is altered. Dopamine activity may promote switching between inputs and outputs of information to specific brain regions. It has been ten years since evidence for a tuning function was advanced for noradrenaline and in the last 5 years the switching hypothesis for dopamine has been tentatively put forward. Recent studies are reviewed to show that while catecholamine activity contributes to neural interactions in separate brain regions that give rise to the organization of different functions, their working principles may be common between species and independent of the nucleus of origin. Behavioral examples are discussed and an attempt is made to integrate this with evidence from intracellular recording studies. It is suggested that the tuning principle in noradrenergic systems is particularly important for the formation of associations and neural plasticity (interference control) and that the switching principle of dopaminergic systems modulates the timing, time-sharing and initiation of responses (program-control).
Hmm, that abstract looks remarkably similar to work published 5, 10, and 20 years later by other (computational-type) investigators, who are older than The Neurocritic1 (and therefore should have some sense of history in the field. for shame! Anyway...)

Fortunately, Trevor Robbins (who has 431 articles listed in Pubmed) started off the morning with a review of the literature. Despite the fact that Professor Robbins has numerous publications of his own on the topic, he cited the work of the late Pat Goldman-Rakic to illustrate that the functional relationship between mesocortical DA activity and optimal cognitive function conforms to the Yerkes-Dodson law of arousal (inverted U-shaped function).

The second speaker, Roshan Cools, presented some interesting data from a small sample of "high" and "low" impulsive subjects, selected from the tails of 1200 students who were screened using the Barratt Impulsiveness Scale. The "high-impulsive" subjects performed worse than the "low-impulsive" on a switching task. Specifically, the cost of switching attention between stimulus types in a visual display was greater in the highly impulsive individuals. Bromocriptine, a dopamine D2 agonist, improved performance in the high-impulsives but impaired performance in the low-impulsive subjects.

But what differences in brain activity were observed, you may ask. Well, they saw changes in basal ganglia2 activity after bromocriptine. So there we have it, presumed differences in baseline DA levels resulting in divergent patterns of performance in the two groups.

1who was a precocious little child in 1985 but aware of that research at the time, I'll have you know.

2a member of the audience, however, asked why the basal ganglia and not the prefrontal cortex, since the study used a switching task. Hmm, could be because D2 receptors are more common in the BG than in the PFC, although the speaker did not use that as a retort. It could also be because the subjects were switching between stimuli rather than switching between abstract rules, but who knows.

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Wednesday, April 12, 2006

Oh the Stigma of It All

The 13th annual meeting of the Cognitive Neuroscience Society was held from April 8-11 in San Francisco. Lots of interesting posters and presentations (and some that were not-so-interesting).

Where shall I begin?

In a less-than-thrilling development for stigmatized groups (pictured above), "disgust" ratings were obtained from Dartmouth students viewing photos of obese people, transgendered individuals, people with mutiple facial piercings (!!), "very ugly" people (not pictured), and "normal-looking" folks (not pictured). Obviously, these sheltered undergrads have never visited a large urban center or the Midwestern U.S.

What do we learn about stereotyping and stigmatization when investigators observe neural activations in regions that [possibly] reflect fear (amygdala) and loathing (insula)? The authors (Krendl et al.) suggest that the study participants were literally having a visceral response to the stigmatized faces.

OK, now we know1 the "neural correlates" of stigma, what shall we do with that information? What does it mean??

Krendl, Kelley, Macrae, & Heatherington (in press). Stigma on the Mind: An investigation of the neural correlates underlying stigma. Social, Cognitive, and Affective Neuroscience.

1well, not really.

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Monday, April 03, 2006

The Sad Cingulate

Yesterday, the New York Times magazine had an article on a new, extremely experimental treatment for depression: deep brain stimulation (DBS) in the ventral portion of the anterior cingulate cortex, in Brodmann's area 25. This procedure, which involves implanting electrodes deep into the brain, has been tested on 12 patients who failed to respond to multiple antidepressant medications and electroconvulsive therapy (8 of them responded to DBS). It works using the same sort of device used in deep brain stimulation for Parkinson's disease, which has been remarkably successful.

A preliminary report on the results was published last year in Neuron.
Deep Brain Stimulation for Treatment-Resistant Depression
Helen S. Mayberg, Andres M. Lozano, Valerie Voon, Heather E. McNeely, David Seminowicz, Clement Hamani, Jason M. Schwalb, and Sidney H. Kennedy
Neuron, Vol 45, 651-660, 03 March 2005

Treatment-resistant depression is a severely disabling disorder with no proven treatment options once multiple medications, psychotherapy, and electroconvulsive therapy have failed. Based on our preliminary observation that the subgenual cingulate region (Brodmann area 25) is metabolically overactive in treatment-resistant depression, we studied whether the application of chronic deep brain stimulation to modulate BA25 could reduce this elevated activity and produce clinical benefit in six patients with refractory depression. Chronic stimulation of white matter tracts adjacent to the subgenual cingulate gyrus was associated with a striking and sustained remission of depression in four of six patients. Antidepressant effects were associated with a marked reduction in local cerebral blood flow as well as changes in downstream limbic and cortical sites, measured using positron emission tomography. These results suggest that disrupting focal pathological activity in limbic-cortical circuits using electrical stimulation of the subgenual cingulate white matter can effectively reverse symptoms in otherwise treatment-resistant depression.
But why stimulate area 25 in depression? Previous neuroimaging studies by Mayberg and colleagues showed that this region is overactive in depression. This excessive activity is dampened in those who respond to SSRIs but remains elevated in those who don't respond to the meds:
Clinical improvement was uniquely associated with limbic and striatal decreases (subgenual cingulate, hippocampus, insula, and pallidum) and brain stem and dorsal cortical increases (prefrontal, parietal, anterior, and posterior cingulate). Failed response was associated with a persistent 1-week pattern and absence of either subgenual cingulate or prefrontal changes.

Mayberg HS, Brannan SK, Tekell JL, Silva JA, Mahurin RK, McGinnis S, Jerabek PA.
Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response.
Biol Psychiatry. 2000 Oct 15;48(8):830-43.

It's a dramatic next step to propose DBS to "turn off" area 25, but at least it's more grounded in the scientific literature than older forms of psychosurgery. Although by no means a trivial operation, DBS doesn't cause permanent damage in the manner of the old-school ablations.

However, statements like these make one a bit concerned about the ethics involved:
The expectations for the Toronto team's D.B.S. study were accordingly modest. When I later asked Mayberg's collaborator Dr. Andres Lozano, the neurosurgeon who performed the operations, what he had expected, he replied, "Nothing."
. . .

Mayberg, who speaks of a "paradigm shift," notes that she developed the trial to evaluate not a treatment but a hypothesis.
It would be really unethical to conduct a controlled treatment trial with a stimulator implanted in some other portion of the brain. The Neuron paper, however, did report on the use of "sham" stimulation (0.0 volts) in area 25 during a blinded, DBS discontinuation period (which seems a reasonable control, given the ethical considerations).

It's a good article (by David Dobbs), but as usual, someone in the popular press had to come up with a ridiculous title:
A Depression Switch?
If it were so simple!

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