Performing-enhancing drugs have seen a lot of recent media attention because of the Mitchell Report. But while most people are busy criticizing the use of such substances, others are trying achieve broader acceptance for them. A German company is selling a product called FPSBrain, where FPS stands for First-Person Shooter. From their website:
FpsBrain was developed doing extensive research to cater to the growing demand for performance improvement in electronic sports. It accelerates neural processes and heightens perception and capacity of reaction and concentration – because not just a first-rate computer or a team well set up are the key to winning a competition, but also the physical and mental condition of each player.
These pills won’t make your muscles huge, rather the ingredients resemble the contents of most energy drinks:
FPSBrain may not contain any novel ingredients, but at the very least it represents a marketing breakthrough. Bringing doping to video games seems to legitimize them as an actual sport while also promising players an elusive edge. Are you concerned that these people are just snake oil salesmen? Don’t worry, the website assures customers “All our staff use FpsBrain at least four times a week to enhance their mental performance and their work efficieny [sic].” So the whole company is hopped up on caffeine pills…and that’s supposed to make me trust them more?
A new paper by Prather et al. identifies song-specific neurons in the swamp sparrow that are active during song perception and song performance. These properties suggest that the neurons might be part of mirroring system analagous to those identified in primates. As far as I can tell, this is the first paper on mirror neurons that Nature has published, though its sibling journals have been kinder to the emerging field (see here and here; note the infamous Iacaboni is an author on both). Because mirror neurons have received extraordinary media attention, sometimes it’s hard to separate the facts from the hype. This Nature paper lends credibility to the field by establishing a small-animal model for future investigation.
Prather et al. measured action potential activity using motorized microdrives that precisely positioned electrodes in the telencephalic nucleus HVC, a brain region known to be involved in singing and song perception. They found that the pattern activity in these regions was nearly identical for auditory perception and song vocalization (see figure below). The authors do note one difference between the neural correlates of action and perception: HVC neurons fired single action potentials during song perception but fired in bursts during song vocalization.
The authors also prove that activity during song vocalization cannot be explained in terms of auditory feedback. For instance, the authors show that HCV activity is not influenced by auditory distractions while a bird is singing. This suggests that activity during singing reflects a corollary discharge from motor systems.
I think the most exciting aspect of this research is the translational potential. Now that we have a small-animal model, it will be easier to test the effects of genetic and pharmacological manipulations on mirror neuron systems. Further research might provide important insights about language acquisition and how it is disrupted in certain pathologies (i.e. autism).
A new paper in the Journal of Consumer Research looks at subliminal influences on consumer decisions, and Science Daily has a great write-up. In the first study, experimenters tested the effect of visual stimuli on preferences regarding delayed gratification:
Li asked participants to act as “photo editors of a magazine” and choose among either appetite stimulating pictures of food or non-appetite stimulating pictures of nature. A control group was shown no pictures at all. All were then asked to participate in a lottery that would either pay them less money sooner or more money later.
Those who had been exposed to the photos of food were almost twenty percentage points more likely to choose the lottery with the chance of a smaller, more immediate payoff than those who were exposed to the photos of nature (61 percent vs. 41.5 percent) and eleven percentage points more likely to choose the short-term gain than those who had not been exposed to any stimulus (61 percent vs. 50 percent).
The second study tested the effect of odor on consumer spending:
Another experiment used a cookie-scented candle to further gauge whether appetitive stimulus affects consumer behavior. Female study participants in a room with a hidden chocolate-chip cookie scented candle were much more likely to make an unplanned purchase of a new sweater — even when told they were on a tight budget — than those randomly assigned to a room with a hidden unscented candle (67 percent vs. 17 percent).
I have a feeling J.Crew is stocking up on cookie candles as we speak…
Marijuana is well-known for its ability to stimulate food intake, so it’s not entirely surprising that cannabinoid receptors are emerging as major targets for weight-contol drugs. European authorities approved sales of the CB1 receptor antagonist rimonabant (Sanofi-Aventis) back in 2006. Now Merck is announcing the development of another CB1 antagonist called taranabant, which reportedly decreases caloric intake. The research appears in the journal Cell Metabolism, but I can’t seem to access the article despite my fancy academic licenses.
Scientific American has a nice summary of the findings:
Heymsfield and his team found that obese people given low doses of taranabant consumed fewer calories, expended more energy and shed pounds. The scientists initially tested the drug on animals, which lost weight on doses that inhibited just 30 percent of their cannabinoid receptors. Armed with this knowledge, the researchers used positron emission tomography (PET) imaging to determine the amount (four to six milligrams) of taranabant that would achieve a similar goal in humans.
They found that obese patients lost significant weight during the 12-week trial at surprisingly low doses ranging from 0.5 to six milligrams; those who took a 12-milligram dose consumed 27 percent fewer calories than subjects given a placebo. The researchers reported that plump participants on the drug also expended more energy while at rest and appeared to burn more fat.
Blocking cannabinoid receptors does not come without a cost:
The medical team said higher doses had some potential negative side effects, most notably nausea, vomiting and moodiness. This was not entirely unexpected, Heymsfield said, given that it has the opposite effect of marijuana, which has been known to quell nausea associated with cancer treatments and, also, to calm rather than irritate people.
Perhaps subsequent pharmaceuticals will specifically target hunger and satiety systems without affecting other aspects of cognition. This is a challenging goal considering how little we know about the mechanism of action for drugs like rimonabant and taranabant. A 2005 Nature Neuroscience review argued that the body’s natural ligands for cannabinoid receptors (endocannabinoids such as anandamide and 2-AG) may operate at two levels. First, basal levels of endocannabinoids act on mesolimbic pathways to facilitate the motivation to eat and the subsequent rewards. Second, the hypothalamus uses endocannabinoids to recruit other hunger hormones after periods of transient food deprivation.
The hypothesis of a dual action in mesolimbic and hypothalamic regions was substantiated by the finding that injection of endocannabinoids into these brain areas stimulates food intake in rats24, 25. Furthermore, endocannabinoid levels vary in both the hypothalamus and the limbic forebrain (but not in the cerebellum, which is not involved in appetite regulation) during the four phases of feeding behavior in rats. These levels are highest during food deprivation and lowest during food consumption, as expected from endogenous orexigenic mediators25. In the hypothalamus, these changes in endocannabinoid levels seemed to be inversely correlated with the changes that are known to occur in blood levels of the neurohormone leptin, which is pivotal in regulating the hypothalamic orexigenic and anoretic signals. Indeed, leptin decreases endocannabinoid levels in the hypothalamus, much as it does for other orexigenic mediators, and obese rodents with defective leptin signaling show significantly higher hypothalamic endocannabinoid concentrations23. It has been suggested that an enhanced endocannabinoid tone is also linked to enhanced ghrelin levels in the bloodstream after food deprivation and may underlie some of the orexigenic effects of this peptide when injected into the rat hypothalamus—effects that are in fact blocked by antagonism at CB1 receptors with rimonabant26.
Despite the multitude of questions that remain to be answered, the development of new drugs like taranabant could help millions of people who struggle with obesity issues. Now that cannabinoid research has established clinical relevance (not to mention profit potential), you can expect to see a lot more of it.
The phenomenon of anesthetic awareness provides great fodder for Hollywood, but now it has also found its way onto the floor of the Supreme Court. Baze vs. Rees challenges the standard 3-drug lethal injection protocol on the basis that it may constitute cruel and unusual punishment, which is outlawed by the eighth amendment.
The current lethal injection protocol was developed in 1977 and consists of a fast-acting barbiturate (sodium thiopental) followed by a paralytic agent (pancuronium bromide) which prevents convulsions during the administration of a heart-stopping toxin (potassium chloride). Arguing on behalf of two Kentucky inmates, attorney Donald Verrilli made the argument that improper administration of the initial barbiturate could cause death row inmates to experience an “excruciating sensation of drowning or strangulation” before they pass away. Because of the paralytic agent, inmates would not be able to communicate their pain to executioners.
A glaring Catch-22 lurks behind this debate: the inmate will not experience pain if the anesthetic is administered effectively, but the American Medical Association (AMA) prohibits healthcare professionals from participating in executions. Interestingly, this hasn’t stopped many doctors from complying with government requests for supervision during executions. Atul Gawande wrote an excellent article profiling these individuals and the issues they face in the New England Journal of Medicine.
Particularly intriguing is the story of Dr. Carlo Musso, who participates in executions despite his personal belief that the death penalty is wrong:
He read about the ethics of participating. He knew about theAMA’s stance against it. Yet he also felt an obligation notto abandon inmates in their dying moments. “We, as doctors,are not the ones deciding the fate of this individual,” he said.“The way I saw it, this is an end-of-life issue, just as withany other terminal disease. It just happens that it involvesa legal process instead of a medical process. When we have apatient who can no longer survive his illness, we as physiciansmust ensure he has comfort. [A death-penalty] patient is nodifferent from a patient dying of cancer — except hiscancer is a court order.” Dr. D said he has “the cure for thiscancer” — abolition of the death penalty — but “ifthe people and the government won’t let you provide it, anda patient then dies, are you not going to comfort him?”
While the article is locked behind a subscription wall, NEJM has posted a free interview with Dr. Musso:
To be sure, these are murky ethical waters. While Dr. Musso makes a valid point about the inevitability of court-ordered executions, it seems like doctor participation sets a dangerous precedent. If doctors begin flouting the AMA’s code of conduct, then what will stop them from cooperating with torture in addition to executions? The U.S. government has already tried to make this happen.
For me, the obvious solution is to abolish the death penalty altogether, an idea that has already caught on in New Jersey. Indeed, Baze vs. Rees may be a veiled attempt to accomplish a similar goal at the national level. Writing for Slate, Dahlia Lithwick makes the point that this case is not really about pharmacology as much as it is about the constitutionality of the death penalty tout court. The Supreme Court’s decision to hear the case has imposed a de facto moratorium on executions across the country. I’m just crossing my fingers that this case doesn’t get closed anytime soon.
Not to be outdone by the New York Times,the Wall Street Journal explores the increasing usage of neuroscience tools for political ends in a recent article. They predict that companies like EmSense, a neuromarketing firm founded by MIT grads that uses EEG headsets to measure the brain activity of consumers and voters, will become increasingly prevalent in future election cycles. Though the ‘08 presidential candidates have stayed away from newfangled gizmos, both John Edwards and Mitt Romney have hopped on the neuropunditry bandwagon to some degree. Romney turned to TargetPoint, a company that offers a new twist on traditional focus groups:
TargetPoint, the Virginia-based political and business consulting firm that worked for the Bush campaign in 2004 and is now working for Mr. Romney (his campaign paid the consultancy $345,000 last quarter, according to Federal Election Commission records) is seeking ways around the problem. Alex Lundry, the company’s research director, says traditional methods of polling voters are sometimes inaccurate. “People may say one thing in a focus group and do another thing in the voting booth,” he says. To get beyond this, Mr. Lundry says, the company developed an Internet survey that asks voters questions like which candidate they support. But rather than just tallying the results, the survey tests their subconscious attitudes by recording how quickly the respondents enter their answers — the theory being that faster responses indicate stronger feelings.
In his studies, which have involved placing partisan voters in brain scanners, he found that when voters look at pictures of candidates or listen to their statements, the regions of the brain associated with emotion are more engaged than the regions governing thought. Instead of detailing a ten-point health-care plan, he says, politicians would be better off talking about health care in moral terms. An October Federal Election Commission filing shows Mr. Edwards’s campaign paid $1,951 to Westen Strategies for air fare. Mark Kornblau, Mr. Edwards’s traveling press secretary, said Mr. Westen had come to observe the candidate and give him some feedback. “He has gained notoriety and respect in the Democratic party with his book,” Mr. Kornblau says. “It was helpful to hear his ideas.” Mr. Westen declined to comment on the discussion.
Of course this news doesn’t do much to dispel the perception that John Edwards is all image and no substance.
It will be interesting to see how voters react to politicians who would rather pander to their emotions than persuade their judgments. The WSJ article argues that voters will accept the application of neuroscience tools to politics just as they have come to accept the use of focus groups. The real question is whether neuromarketing strategies will actually pay off in the primaries, and that only time can tell.
Currently I am running a study that examines the effects of chronic nicotine on sensory processing in mice. While I don’t mind coming into the lab on weekends, the prospect of visiting my animals 24/7 to inject nicotine wasn’t exactly practical. I could give daily or twice daily injections, but even that doesn’t really come close to approximating the behavior of human smokers.
That’s why we turned to a company called Alzet that manufactures miniature pumps for drug delivery in laboratory animals. These pumps can deliver small volumes of drug solution at a controlled rate over a period of up to six weeks. We opted for the 2002 model, with a reservoir volume of 0.2 mL and a flow rate of 0.5 µL/hr.
They are pretty easy to use: Just fill up the reservoir with concentrated drug solution and pop on the cap. Then, anesthetize the rodent and cut a small slit in its back using standard aseptic techniques. After opening a small cavity for the pump with a hemostat, insert the device and close the opening using medical staples.
After implanting these pumps subcutaneously, I couldn’t help but wonder if these things were actually going to work. How could a little piece of plastic control the flow of drug solution so precisely? If they worked because of osmotic pressure, then shouldn’t the flow rate depend on the concentration of the dissolved drug? I knew that osmotic pumps were popular, but I couldn’t shake the irrational fear that these $20 devices were just one big scam.
The only way I could settle my nerves was by figuring out how the devices worked. Luckily Alzet’s website is relatively transparent about the mechanism. Now I know that the osmotic pressure difference is actually between the animal’s body and the “salt sleeve” that surrounds the drug reservoir. From their website:
ALZET pumps operate because of an osmotic pressure difference between a compartment within the pump, called the salt sleeve, and the tissue environment in which the pump is implanted. The high osmolality of the salt sleeve causes water to flux into the pump through a semipermeable membrane which forms the outer surface of the pump. As the water enters the salt sleeve, it compresses the flexible reservoir, displacing the test solution from the pump at a controlled, predetermined rate. Because the compressed reservoir cannot be refilled, the pumps are designed for single-use only.
The rate of delivery by an ALZET pump is controlled by the water permeability of the pump’s outer membrane. Thus, the delivery profile of the pump is independent of the drug formulation dispensed.
Pretty nifty, huh? Even niftier is the accompanying animation:
Now I am much more confident that my mice are indeed receiving the expected dose of nicotine. In retrospect my fears were misplaced, but in science it never hurts to be skeptical/cautious.
Performing-enhancing drugs have seen a lot of recent media attention because of the Mitchell Report. But while most people are busy criticizing the use of such substances, others are trying achieve broader acceptance for them. A German company is selling a product called FPSBrain, where FPS stands for First-Person Shooter. From their website:
That’s why we turned to a company called 
