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Friday, September 11, 2009

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Wednesday, September 9, 2009

Deep Brain Stimulation for Severe Alcoholism

Deep brain stimulation (DBS) for treatment-refractory psychiatric disorders has been gaining in popularity. The procedure involves neurosurgery to implant stimulating electrodes aimed at a target region inside the brain. It works using the same sort of pacemaker-like device used for DBS in Parkinson's disease, which has been remarkably successful at alleviating symptoms. DBS as a treatment for neurological disorders such as Parkinson's, primary generalised dystonia, atypical tremor syndromes, cluster headache, phantom limb pain, and epilepsy has been mostly unobjectionable.

However, the Neurological/Psychiatric Divide makes DBS for mental illnesses such as major depression and obsessive compulsive disorder more ethically problematic. A new paper in the Archives of General Psychiatry (Rabins et al., 2009)¹ summarizes a consensus conference held on this and related issues (such as human subjects protection and the design of clinical trials). A list of 16 guidelines was issued, which included the following:

2. Deep brain stimulation for disorders of MBT [Mood, Behavior, and Thought] is at an early proof-of-principle stage and must be considered investigational. Currently, no single target has been validated or demonstrated to be superior to others in any disorder of MBT. Therefore, it is premature to rule out the study of new implantation sites that have a good scientific rationale...
3. The comparative efficacy and safety of DBS vs other treatments, including ablative surgery, should be studied further. Such studies are ethical and scientifically necessary.
4. Given its history, neurosurgical intervention for disorders of MBT is a socially and culturally sensitive area of research and practice. Therefore, DBS for disorders of MBT should be studied in carefully designed trials and should be performed only at expert centers that are participating in such trials and that adhere to the highest scientific, clinical, and ethical standards.
. . .
12. The consent process should include discussion of what is and is not known about long-term consequences of DBS. Potential adverse outcomes include potentially limiting participation in future research, inability to use certain other treatments, and an inability to undergo certain tests. ... Additionally, the consent process should state explicitly that, even with positive outcomes, DBS for disorders of MBT is unlikely by itself to improve all aspects of the individual's mood, function, and interpersonal relationships: DBS is only one aspect of a comprehensive treatment program.

The specific indications mentioned by Rabins and his 18 co-authors were major depression, obsessive-compulsive disorder, and Tourette syndrome. Severe alcohol dependence was not included as one of the disorders. DBS for alcoholism sounds rather drastic, doesn't it? Nonetheless, a German research group led by Hans-Jochen Heinze (et al., 2009) was not deterred. They recently reported results from 3 male patients² with severe and refractory alcohol dependence as part of a small clinical trial that will ultimately include 10 patients.

Inclusion criteria are: male gender, age 25–60 years, finished detoxification and subsequent period of abstinence of at least 2 weeks. Moreover, the patients are required to have demonstrated treatment failures of at least two inpatient programs of at least 6 month duration, failure of anti-craving substances (e.g., acamprosate, naltrexone), failure of community and self-help programs. ... Patients are excluded, if they meet any of the following criteria: seizures during the detoxification phase, high score on neuroticism scales, antisocial personality disorder, clinically significant impairments on a neuropsychological test battery Further exclusion criteria were circumscribed brain damage or marked atrophy on MRI, alcohol-related personality change, and use of additional addictive substances.

The target region? The nucleus accumbens (NAcc), the “Universal Addiction Site” -- an oversimplification, they admit, but still, the NAcc is...

...a central place in orchestrating the events related to the “wanting” [Robinson & Berridge, 2008] of alcohol on the one hand and drug-induced neural sensitization on the other hand. Anatomically, the NAcc receives inputs from the prefrontal cortex on the one hand and limbic structures such as the hippocampus and amygdala on the other. This circuitry allows for the integration of contextual information arising from hippocampus and emotional information coming from the amygdala with cognitive information supplied by the PFC in the selection of goal-directed behaviors in general and behaviors related to drug “wanting” in particular, which is why the NAcc has been called a limbic-motor interface.

Since anatomical information was not illustrated in the current paper, a figure from the earlier work of Schlaepfer et al., (2007) is presented below.

The topographical location of the nucleus accumbens in relation to other brain structures on a horizontal plane 3 mm below the AC-PC plane (Schlaepfer et al., 2007).

That protocol was designed to relieve anhedonia (inability to experience pleasure from normally pleasurable life events) in major depression. Why not stimulate the "pleasure center" when you're feeling blue? Extensive research in animals and humans has demonstrated "hedonic hot spots" (Pecina et al., 2006) [or "liking" of pleasant sensory experiences] in the NAcc that respond to food and pharmaceutical and financial and sexual rewards.

But what are the procedures for targeting the same region to reduce reward and pleasure? Well, we don't know from reading Heinze et al. (2009): "Details regarding the stimulation protocols in the different patients can be found elsewhere" [insert citation of an in press paper that is not online yet]. Details on the "clinical aspects" are pretty sparse and the focus is on the "basic science aspects" (electrophysiological recording and cognitive task performance to assess action monitoring and the salience of drug-related cues).

Was the DBS treatment effective? All patients had failed multiple detox treatments, withdrawal therapies, and drug trials (acamprosate). Until the other paper is published, we have only anecdotal reports in the Methods.

Patient HM (age 36) had started to drink alcohol at age 12 and had a family history of alcoholism (father and two uncles). ... The patient was implanted on October 5, 2007 and has been abstinent since then. There were no psychological changes after the operation. The patient reported to have no craving symptoms and that he is thus able to derive pleasure from daily activities of life. He has found a job and has established new social contacts.

Patient GM (age 37) had started to drink alcohol at age 11 and had a positive family history (father, mother, several other relatives). ... Following the operation (January 13, 2008) this patient experienced a period of hypomania which stopped after stimulation parameters were changed. The patient has been abstinent since the operation and reports a complete reduction of his reaction to alcohol-related cues and craving.

Patient TM (age 40) had been alcohol-dependent since age 18 and had a positive family history (father). ... The patient was operated on September 13, 2007 and showed no psychological abnormalities in the postoperative period. He was fully abstinent until September 2008. Subsequently, he has experienced short periods of relapse of 1–2 weeks duration (10 weeks in the past 16 months). The patient remarked that he had never felt as good as currently and reported a considerable reduction in his reaction to alcohol-related cues.

To be continued....

Footnotes

1 Guidelines were also published by the German Deep Brain Stimulation Association (Voges et al., 2009).

² "A fourth had been implanted but electrodes had to be removed because of an infectious complication."

References

Heinze, H. et al. (2009). Counteracting incentive sensitization in severe alcohol dependence using deep brain stimulation of the nucleus accumbens: clinical and basic science aspects Frontiers in Human Neuroscience, 3. DOI: 10.3389/neuro.09.022.2009

Pecina S, Smith KS, Berridge KC. (2006). Hedonic hot spots in the brain. Neuroscientist 12:500-11.

Rabins, P. et al. (2009). Scientific and Ethical Issues Related to Deep Brain Stimulation for Disorders of Mood, Behavior, and Thought. Archives of General Psychiatry, 66 (9), 931-937.

Robinson TE, Berridge KC. (2008). Review. The incentive sensitization theory of addiction: some current issues. Philos Trans R. Soc Lond B Biol Sci. 363:3137-46.

Schlaepfer TE, Cohen MX, Frick C, Kosel M, Brodesser D, Axmacher N, Joe AY, Kreft M, Lenartz D, Sturm V. (2008). Deep Brain Stimulation to Reward Circuitry Alleviates Anhedonia in Refractory Major Depression. Neuropsychopharmacology 33:368–377.

090909090909

In Chinese numerology the number 9 is a homophone of the word for "long-lasting". So today seems like a good day to do something that will last a long time, right? However, from AgarAgar we learn:

Today sounds like a nice date to remember.. 090909.. Lots of ple say it a good date for marriage.. 999 in Chinese means long-lasting. However, as it falls in the lunar 7th mth, aka ghost mth. Therefore no much weddings are held on this date. Maybe some ROMs or non-chinese are having weddings today bah.

In contrast, 080808 was such a lucky number that the Opening Ceremony of the 2008 Olympics in Beijing began at 8:08PM on 08/08/08.

The vagueness of Western Numerology is much like reading your horoscope or going to a fortune teller. Here's some information on the number nine:

In Numerology, the positive characteristics of nine (9) are selflessness, fulfillment, completion, universality, universal understanding, interrelatedness, compassion, idealism tolerance, forgiveness, generosity, benevolence, humanitarianism, emotionalism, and justice. Nine is also associated with accomplished artists and thinkers who are inspired by universal truths. Simultaneously, 9 can represent negative characteristics, from selfishness to extravagance to vulgarity -- essentially the opposites of the positive characteristics.

How very useful and specific!!

From nmnl’s posterous.

Saturday, September 5, 2009

RULE 34: WHAT NETPORN TELLS US ABOUT THE BRAIN

That is (or was) the title of a book by Ogi Ogas and Sai Gaddam,¹ to be published by Dutton in 2010. How on earth do I know this? Back in July, The Neurocritic noticed a number of visitors to the post Voodoo Correlations in Social Neuroscience (about the infamous paper by Vul et al.) who came from a link on the LiveJournal of shaggirl. Specifically, the traffic was from her entry A response from our friendly scientists... I took note of it, thought I might write about it but other topics took precedence. But this week, a larger surge of visitors arrived from various LiveJournal sites.² The reason? Let's start at the beginning.

Shaggirl was "contacted by a couple of guys researching and writing about online fanfic."

Hi, Shaggirl:

I'm a cognitive neuroscientist at Boston University writing a book for Dutton (an imprint of Penguin) about how the Internet reveals new insights into some of the oldest circuits in our brain which control romantic attraction and sexual behavior. I was very much hoping you might be willing to chat about Crack Van on LJ.
. . .
For our research, we're quite interested in learning about how people creatively use text and fiction to express and explore sexuality. If you're willing, we'd like to ask questions about Crack Van and about adult fanfic in general. If you'd like, we'd be happy to include a positive mention of you and/or Crack Van in the book (or respect your privacy, if you'd prefer).
If you have any questions about our research or book, please don't hesitate to ask! I look forward to hearing from you! :)
Dr. Ogi Ogas
Department of Cognitive and Neural Systems
Boston University

I do not want to begin a lengthy discourse on fan fiction, other than to quote Wikipedia:

Fan fiction (alternately referred to as fanfiction, fanfic, FF, or fic) is a broadly-defined term for fan labor regarding stories about characters or settings written by fans of the original work, rather than by the original creator. Works of fan fiction are rarely commissioned or authorized by the original work's owner, creator, or publisher; also, they are almost never professionally published. Fan fiction, therefore, is defined by being both related to its subject's canonical fictional universe and simultaneously existing outside the canon of that universe.

So who is Ogi Ogas? While a grad student at Boston University, he entered a well-known game show, won $500,000 and wrote about it in SEED magazine:

Who Wants to Be a Cognitive Neuroscientist Millionaire?
A researcher uses his understanding of the human brain to advance on a popular quiz show.

Even with all 4 choices available, it's obvious the answer is D ("Heroin: the sedative for coughs"). Prescription cough syrup contains codeine, which is a cough suppressant. [However, it is easy to say that when the stakes are nil. ANYWAY.]

In response to some questions about their book project, Gaddam replied:

Before putting any questions, let me give a brief overview of our scientific perspective and how it will inform the book. As cognitive neuroscientists, we are respectful of the fascinating diversity of the neural landscape. And this diversity, we believe, is reflected in the terrain of erotic fantasy.
The internet and e-publishing now allow for a revolutionary and unprecedented disclosure of all our fantasies, not just those decided as marketable and mainstream for print. Digital publishing seems to have lead to an explosion in the array of fantasies we can now experience and learn from; the loop of imagination, desire, and actuality is now tighter. We want to 'neuro-scientifically' explore what this blossoming of fantasy means for us as individuals, and as a society. How does this access to all manner of fantasies imaginable change our brains?
Given this broad overview, we have some specific questions, and more general ones about adult fanfic, that we are hoping you can help us with. I do apologize if some questions seem naive and/or I inadvertently mis-characterize something in my ignorance!

He then goes on to ask a number of questions about adult fanfic. Dana (shaggirl) replied in a lengthy, thoughtful post in which she explains fandom ("composed primarily of well educated women, most of whom self-identify as geeks"), objects to the word "netporn" in their book title, and answers all 7 questions. Then A response from our friendly scientists... where yours truly gets a mention:

. . .

One quick note about the subtitle of the book: the current title is largely driven by the pre-publication marketing needs of the publication industry, and was determined by our editor. The eventual subtitle will likely change; it may still contain the term netporn, though this is increasingly unlikely [NOTE: Unlike the screenshot above, the current book project list from Gail Ross shows the NETPORN subtitle has indeed been removed]. ...

In terms of turning this into hard science, our primary goal is to make a strong case for the study of fantasy as being accessible in this era of copious datastreams from humans. To give you one example of the kind of current study in neurosexual behavior that we feel is quite limited, there was an article in the Time magazine (http://www.time.com/time/health/article/0,8599,1911103,00.html) on how girls focus more on best friends while boys are more interested in group dynamics and 'packs'. The authors of the study tied this observation to the differential activation patterns in the brain based on how the subject group of boys and girls rated pictures of strangers. The article state that the "nucleus accumbens (which is associated with reward and motivation), hypothalamus (associated with hormone secretion), hippocampus (associated with social learning) and insula (associated with subjective feelings) all become more active."

The suspect and cavalier methodology of this study evoke some of the general problems that plague brain imaging experiments that purportedly examine social behavior [1]. We hope to make the case that such methodological contortions are not required when a vast pool of people provide behavioral data on the internet through quantifiable activity.

Polling feedback from groups would be immensely useful. We would definitely love your help in reaching other fans...

[1] Here's a paper criticizing such casual treatment of the brain-behavior linkage, which has received a lot of attention in the neuroscience community (http://cns.bu.edu/~gsc/Articles/Vul_09_Voodoo.pdf). The content requires an understanding of imaging methodology, but the abstract is definitely accessible. Here's a posting from a popular neuroscience blog describing the article (http://neurocritic.blogspot.com/2009/01/voodoo-correlations-in-social.html)

Two things:

(1) They said the content of their book will be "Using new digital sources of data to illuminate brain regions and neural pathways involved in romantic and sexual behavior." However, they did not actually propose to measure brain function at all. They might be skeptical of fMRI, but it's a lot better than no real neural data at all.

(2) A poll. That generated an enormous amount of controversy in the fanfic community. [They're a very prolific bunch.] Hundreds of posts. Thousands of comments.

SurveyFail - an entire wiki devoted to the controversy.

For Science!

The poll was taken down (although you can view the questions elsewhere: part 1, part 2) and the ogi_ogas LiveJournal deleted (but here's a remnant):

So what kind of scientists are you anyway?
We're brain modelers. We're aligned with the relatively new field of cognitive neuroscience...
. . .
Our current research project will result in a model that makes novel behavioral and physiological predictions.

From a poorly written survey? And just when you think their project is a wee bit grandiose, the pomposity reaches stunning proportions:

The greater one's mathematical ability, the greater the opportunity for designing a powerful and sophisticated model. Superior models, such as those of Stephen Grossberg and Gail Carpenter, may include unsolvable systems of differential equations. Still, useful and productive models can be constructed using relatively straightforward mathematics.

Oh, and here's a ridiculous question:

How is straight female interest in slash fiction like straight male interest in "shemale"* models? And why in the world does this matter?
* ...We are aware that the term "shemale" may be used as a pejorative, but we are here referring to the narrowly defined term used in the adult industry for certain models.

One does not need to be an expert in any of these fields to see the problems inherent in the Ogas and Gaddam approach of inferring brain function from data on netporn usage (broadly construed) and unscientific polls. But it gets worse...

The structure and activity of our subcortical circuits are shaped by neurohormones such as testosterone, estrogen, oxytocin, progesterone, and vasopressin; these circuits function differently in men and women. As cognitive neuroscientists, we draw upon a wide variety of empirical data sources to model these circuits, including brain imaging studies, primate research, cognitive science experiments, machine learning algorithms--and behavioral data. The Internet offers large, unprecedented sources of data on human activity: one of these data sets is fan fiction.
We're deeply interested in broad-based behavioral data that involves romantic or erotic cognition and evinces a clear distinction between men and women. Fan fiction matches this criteria perfectly. Let us make clear, however: fan fiction is not the subject of our research. Our subject is the human brain. For us, fan fiction is a wonderfully rich source of data--like single-neuron recordings in rhesus monkeys--albeit a unique and invaluable one.

...because fan fiction is just as precise as single-unit recording at revealing putative sex differences in subcortical circuits. In spite of a wink and a nod to "erotic cognition" Ogas & Gaddam reveal elsewhere in their manifesto that they're not at all interested in cortical function.

Furthermore, were the ethics of conducting research on human subjects taken into consideration? Did the pair have proper approval from Boston University's Institutional Review Board? Here's deadlychameleon's investigation:

I called the Boston University IRB office. The direct approach works.
They've gotten a lot of emails regarding Dr. Ogas. He is no longer in any way affiliated with Boston University, except as a recent graduate. They have asked him to stop using his official Boston University email address in connection with this project, or his website. He is officially on his own, and this project is NOT IRB APPROVED.
That is the official status as stated by the Boston University IRB office.

And in the end, from a neuroscientific viewpoint, the premise of their work was fatally flawed. Dutton, are you listening?

Footnotes

¹ You'll notice these links are from the Google cache, because they took down their websites after the resulting furor. Both are recent graduates from the Department of Cognitive and Neural Systems at Boston University. Gaddam had not yet updated his resume to reflect this.

² Other visitors were from dreamwidth.org, a LiveJournal knockoff that had escaped my awareness until now.

Friday, September 4, 2009

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