Sunday, July 31, 2011

Science Doesn't Say

How many times have you heard someone say that "science tells us" - or that it shows, reveals, says, proves, or makes clear?

It's very common. But it's misleading.

Scientists never talk like this while they're doing science, which suggests that there's something wrong with it. Rather, we say: "Our experiment was inspired by the fact that X, which was shown last year by Y et al".

Y et al aren't just some bunch of famous smart guys who came up with an idea and told everyone, and everyone believed them, because scientists respect authority - which is what "Science Says" means.

No, Y et al is a paper, or other report, and when we say that it shows something, we mean it quite literally. Scientific data is like a photograph or, more accurately perhaps, a window, through which we can just see X.

'Science' is nothing special. It's just looking at stuff.

Indeed, there are scientific papers where the key result is literally a photo, usually taken down a microscope or through a telescope, but still. This paper is a great example. The key result was that the little yellow thing in the third image grew some extra sprouts from day 0 to day 1. It takes some knowledge of the context to understand why that's so interesting, but the actual result is right there.

However, even where the result isn't literally a picture, it is still a window.

This line shows the chemical composition of a particular part of someone's brain. Each of the peaks on the curve corresponds to a particular chemical, and the height of the peak tells us how much of that chemical there is.

There's nothing mysterious about why particular chemicals cause particular peaks. It's well understood. (Conceptually, it's like each molecule is a bell, of a particular size and shape, and they make different sounds when you shake them around. The line is what you get when you shake the piece of brain up, and record how much of each sound you hear back.)

Getting this data is a high tech process requiring special equipment, but all that's just background detail when you actually come to do it. Just as a photographer doesn't need to worry about the mechanics of their camera, and you don't need to worry about how your eye gathers and focusses light as you're reading this.

There is an element of authority and trust in science, but not in any special sense. To take published evidence at face value, you do need to trust that the authors haven't manipulated it, and to trust that they gathered it in the way they described.

But the same goes for any other kind of evidence. Any photograph could be Photoshopped, or the caption could be misleading. Anything you read could be made up. In everyday life, we don't worry about this unless there's a particular reason to.

A scientific journal is just a newspaper with access to better equipment.

There's a view in which "Science" is a kind of oracle that hands down judgements from on high, with scientists as priests who record and proclaim the revelations. This leads to no end of problems.

It easily leads to the view that science is somehow especially hard to understand, or even that we can't understand it, so there's no point in trying. It can lead to the idea that science can't be very interesting compared to the real world. It leads to questions what good it can do, or whether science can ever answer 'the big issues'.

When you realize that science is just looking at stuff, you see that those concerns, far from being valid, don't even make sense.

Friday, July 29, 2011

What Big Eyes You Have

According to the BBC, a new study has found that northern peoples have bigger eyes - and bigger brains.

Actually, the paper in question talked about eyes but didn't make much of the brain finding, which is confined to the Supplement. Nonetheless, they did find an effect on brain size too. Peoples living further from the equator have larger eye sockets and also larger total cranial capacity (brain volume), apparantly. The authors include Robin Dunbar of "Dunbar's Number" fame.

Their idea is that humans evolved larger eyes because further from the equator, there's on average less light, so you need bigger eyes to collect more light and see well.

They looked at 19th century skulls stored in museum collections, and measured the size of the eye sockets (orbits). They did this by filling them with a bunch of little glass balls and counting how many balls fit. They had a total of 73 "healthy adult" skulls from 12 different places, ranging from Scandinavia to Kenya.

Latitude essentially meant northern-ness because only one population (Australian Aborigines) were from far south of the equator.

Total brain size also increased with latitude, but eye size increased even faster, so the eye:brain ratio increased. They don't really discuss the brain size finding, except to suggest that it might be accounted for by increased visual cortex (though there's no direct evidence of that), but here it is, showing latitude vs. cranial capacity in ml.

The idea that northern peoples are brainier unfortunately has a long history. For example, it's been suggested that the coldness of northern climes meant that life was harder, so people evolved to be smarter to survive.

The heat of the Sahara was easy living compared to the deadly horrors of an English winter, in other words. Hmm.

The idea that higher latitudes are darker, so you'd need bigger eyes, and then a bigger brain (at least the visual parts of the brain) to process what you see, is certainly more plausible than that theory. However, the data in this paper seem pretty scanty.

Measuring skulls by filling them with little balls was cutting edge neuroscience in the 19th century. However, nowadays, we have MRI scanners. Although usually intended to image the brain, many MRI scans of the head also give an excellent image of the skull and eyes. Millions of people of all races get MRI scans every year.

Nowadays, people have medical records, so we can tell exactly how healthy people are. The people who became these skulls in a museum were said to be healthy, but how healthy a 19th century Indian or Kenyan could hope to be, by modern standards, I'm not sure. Certainly there's an excellent chance that they were malnourished and I suspect this would make your eyes and skull smaller.

ResearchBlogging.orgPearce, E., & Dunbar, R. (2011). Latitudinal variation in light levels drives human visual system size Biology Letters DOI: 10.1098/rsbl.2011.0570

Wednesday, July 27, 2011

Dhoni Bhaji controversy exposes liquor companies surrogate ad campaign...Keep it up Dhoni ji Yes, you made it large..

Suneel Vatsyayan conducted mentor cum training program for Dr.Roslee Ahmed Lecturer Counseling, Universiti Teknologi Malaysia

Suneel Vatsyayan conducted a personalized mentor cum training program for Dr.Roslee Ahmed Lecturer Counseling, University Teknologi Malaysia, has successfully participated in mentorship cum training program (19th .20th & 21st July 2011) on drug addiction & sexual behaviour. The purposes of this program is giving theory and practical using the counseling approaches in handling client facing  challenges like drug addiction and its related issues  sexual behavior, relapse ,rehabilitation etc.. Dr.Roslee Ahmed also visited Peer led Nai Kiran De-addiction center Narela. Mr.Vatsyayan is a consultant and trainer to Bharat Bhushan  and Naikiran Society.
Bharat Bhushan Nai Kiran ,Suneel Vatsyayan and  Dr.Roslee (from left to right) 

Brain Connectivity, Or Head Movement?

"It's pretty painless. Basically you just need to lie there and make sure you don't move your head".

This is what I say to all the girls... who are taking part in my fMRI studies. Head movement is a big problem in fMRI. If your head moves, your brain moves and all fMRI analysis assumes that the brain is perfectly still. Although head movement correction is now a standard part of any analysis software, it's not perfect.

It may be a particular problem in functional connectivity studies, which attempt to measure the degree to which different parts of the brain are "talking" to each other, in terms of correlated neural activity over time. These are extremely popular nowadays. It's even been claimed that this data may help us understand consciousness itself (although we've heard that before).

A new paper offers some important words of caution. It shows that head motion affects estimates of functional connectivity. The more motion, the weaker the measured connectivity in long-range networks, while shorter range connections were stronger. Also, men tended to move more than women.

The effect was small - head movement can't explain more than a small fraction of the variability in connectivity.

The authors looked at 1,000 scans from healthy volunteers. They just had to lie in the scanner at rest. They looked at functional connectivity, using standard "motion correction" methods, and correlated it with head movement (which you can measure very accurately from the MRI images themselves.) Men tended to move more than women. Could this explain why women tend to have higher functional connectivity?

Disconcertingly, head movement was associated with low long range / high short range connections, which is exactly what's been proposed to happen in autism (although in fairness, not all the evidence for this comes from fMRI).

This clearly doesn't prove that the autism studies are all dodgy, but it's an issue. People with autism, and people with almost any mental or physical disorder, on average tend to move more than healthy controls.

One caveat. Could it be that brain activity causes head movement, rather than the reverse? The authors don't consider this. Head movement must come from the brain, of course. Probably from the motor cortex. The fact that motor cortex functional connectivity was positively associated with movement does suggest a possible link.

However, this paper still ought to make anyone who's using functional connectivity worry - at least a little.
Head motion is a particularly insidious confound. It is insidious because it biases between-group studies often in the direction of the hypothesized difference....even though there is considerable variation that is not due to head motion, in any given instance, a between-group difference could be entirely due to motion.

ResearchBlogging.orgVan Dijk, K., Sabuncu, M., & Buckner, R. (2011). The Influence of Head Motion on Intrinsic Functional Connectivity MRI NeuroImage DOI: 10.1016/j.neuroimage.2011.07.044

Monday, July 25, 2011

Ban These Sick Ape-Man Frankensteins

According to a new report, urgent action is required to stop scientists creating a monstrous race of apes with fully functional human brains (just as Christine O'Donnell warned us about those mice), thus causing Planet Of The Apes to come true.

OK, that's not quite what the Academy of Medical Sciences said. But judging from most of the media coverage, you might think it was.

The report is actually about "Animals containing human material" and it notes that under British law, experiments of this kind are covered by generic animal research rules, but there are no special animal-human regulations.

Should there be?

I think there should be. We as a society allow experiments on animals or animal embryos that we don't allow on humans, even on human embyros. Clearly, we need to decide what we're going to do about organisms that have both human and animal DNA, or whatever. This doesn't mean restricting it - to clear up the rules could also facilitate such research, by making it explicit what is allowed.

However, we should tread carefully here. This is an area where our intuitions can lead us astray.

Although we have absolutely no idea how to make an animal-human "hybrid", or even whether it's possible at all, the very idea of it has many people worried. It's probably a case of the uncanny valley and lots of cultural baggage (Planet of the Apes et al).

So, for whatever reason, we have a hang-up about making monstrous ape-men. Fair enough. So long as we remember that this is entirely hypothetical, and that it might, for all we know, be literally impossible.

Yet other things in this debate are very real. Over-zealous regulation of research could easily end up delaying, say, a cure for Alzheimer's for, say, 10 years. That would be dooming tens of millions of people to suffering and death.

The problem is, that's hard to picture. It's hard to imagine how bad Alzheimer's is unless you have personal experience. Even if you do, it's hard to multiply that badness by ten million anonymous, hypothetical people. "One ape-man is a tragedy; a million deaths is a statistic".

Delaying science is easy to do (for politicians), and hard to picture why it's bad. Whereas "a monstrous ape-man" is the exact opposite. Easy to imagine - just look at the media interest in this story - yet nowhere close to being reality.

This is a problem. The human mind and the way we think about these issues is a problem. Even when that mind is safely inside a nice normal human skull.

Saturday, July 23, 2011

The Dire Affects Of Substance Abuse

From major cities to small town America, the incidence of substance abuse is a problem that has reached out of control proportions. It often begins with young teens, who feeling under pressure from their peers, make the choice to give using a drug a try. For some that is all it takes. One incident leads to two, until the user is hooked to a lifetime of drug abuse. Oklahoma substance abuse is not immune from these problems.

Depending on the drug of choice and how often it is used, it can be difficult to determine who the abuser is. They become experts at hiding the problem from family or relatives. In addition, there are family members who are suspicious, but remain in denial. They just cannot allow themselves to admit that their loved one is using illegal drugs.

In today's society, there are very few families that do not know of at least one member that has a problem with drugs. It could be a son or daughter; brother or sister; niece or nephew. Substance abuse does not discriminate and is an equal opportunity addictive agent. Problems can begin with a few drinks of alcohol, and once under the influence a user is more apt to be susceptible to trying other substances. A person is under the illusion that if they handle one drug well, they will be able to handle others.

The first thing one has to do is watch for ways to recognize someone who may have a problem with illegal drugs. If of school age, they may be missing more and more school and losing interest in school activities. Money and valuables may come up missing from around the home as drug use is an expensive habit. Personality changes and odd behavior are often noted.

Caring family members will sometimes set up traps and try and catch the abuser or locate their 'stash.' Even when confronted under these conditions, the addict will deny all use. Very few will admit to having a problem. They foolishly see themselves as the ones in charge and they are capable of handling the situation. It is a once and a while thing that is only done for kicks. Any possible excuse is better than the alternative of facing life drug free.

The truth of the matter is that help is available. Yet, unless one is caught breaking the law while using, or is still young enough to be under parental control, there is not a lot that can be done to stop the abuser. Only in a few cases where they have hit rock bottom, do some abusers reach out for help. Usually the thought of entering rehab and having no access to their drug of choice, is the very thing that keeps many from entering.

Occasionally, getting a user to go for counseling with a highly trained dependence facilitator can get them to begin to see the error of their ways. There are those who will begin to see that that drugs are controlling their lives. They will begin to see the error of their ways and want to work toward a drug free life. Sadly, these people are the exception and we are helpless in stopping the loss of life to drug addiction. Oklahoma substance abuse is as critical a situation as it is in all of our United States, and the journey back to health for many be a long and difficult one.

Friday, July 22, 2011

New Antidepressant - Old Tricks

The past decade has been a bad one for antidepressant manufacturers.

Quite apart from all the bad press these drugs have been getting lately, there's been a remarkable lack of new antidepressants making it to the market. The only really novel drugs to hit the shelves since 2000 have been agomelatine and vilazodone. There were a couple of others that were just minor variants on old molecules, but that's it. Quite a contrast from the 1990s when new drugs were ten-a-penny.

This makes "Lu AA21004" rather special. It's a new antidepressant currently in development and by all accounts it's making good progress. It's now in Phase III trials, the last stage before approval. And a large clinical trial has just been published finding that it works.

But is it a medical advance or merely a commercial one?

Pharmacologically, Lu AA21004 is kind of a new twist on an old classic . Its main mechanism of action is inhibiting the reuptake of serotonin, just like Prozac and other SSRIs. However, unlike them, it also blocks serotonin 5HT3 and 5HT7 receptors, activates 5HT1A receptors and partially agonizes 5HT1B.

None of these things cry out "antidepressant" to me, but they do at least make it a bit different.

The new trial took 430 depressed people and randomized them to get Lu AA21004, at two different doses, 5mg or 10mg, or the older antidepressant venlafaxine at the high-ish dose of 225 mg, or placebo.

It worked. Over 6 weeks, people on the new drug improved more than those on placebo, and equally as well as people on venlafaxine; the lower 5 mg dose was a bit less effective, but not significantly so.

The size of the effect was medium, with a benefit over-and-above placebo of about 5 points on the MADRS depression scale, which considering that the baseline scores in this study averaged 34, is not huge, but it compares well to other antidepressant trials.

Now we come to the side effects, and this is the most important bit, as we'll see later. The authors did not specifically probe for these, they just relied on spontaneous report, which tends to underestimate adverse events.

Basically, the main problem with Lu AA21004 was that it made people sick. Literally - 9% of people on the highest dose suffered vomiting, and 38% got nausea. However, the 5 mg dose was no worse than venlafaxine for nausea, and was relatively vomit-free. Unlike venlafaxine, it didn't cause dry mouth, constipation, or sexual problems.

So that's lovely then. Let's get this stuff to market!

Hang on.

The big selling point for this drug is clearly the lack of side effects. It was no more effective than the (much cheaper, because off-patent) venlafaxine. It was better tolerated, but that's not a great achievement to be honest. Venlafaxine is quite notorious for causing side effects, especially at higher doses.

I take venlafaxine 300 mg and the side effects aren't the end of the world, but they're no fun, and the point is, they're well known to be worse than you get with other modern drugs, most notably SSRIs.

If you ask me, this study should have compared the new drug to an SSRI, because they're used much more widely than venlafaxine. Which one? How about escitalopram, a drug which is, according to most of the literature, one of the best SSRIs, as effective as venlafaxine, but with fewer side effects.

Actually, according to Lundbeck, who make escitalopram, it's even better than venlafaxine. Now, they would say that, given that they make it - but the makers of Lu AA21004 ought to believe them, because, er, they're the same people. "Lu" stands for Lundbeck.

The real competitor for this drug, according to Lundbeck, is escitalopram. But no-one wants to be in competition with themselves.

This may be why, although there are no fewer than 26 registered clinical trials of Lu AA21004 either ongoing or completed, only one is comparing it to an SSRI. The others either compare it to venlafaxine, or to duloxetine, which has even worse side effects. The one trial that will compare it to escitalopram has a narrow focus (sexual dysfunction).

Pharmacologically, remember, this drug is an SSRI with a few "special moves", in terms of hitting some serotonin receptors. The question is - do those extra tricks actually make it better? Or is it just a glorified, and expensive, new SSRI? We don't know and we're not going to find out any time soon.

If Lu AA21004 is no more effective, and no better tolerated, than tried-and-tested old escitalopram, anyone who buys it will be paying extra for no real benefit. The only winner, in that case, being Lundbeck - especially given that escitalopram goes off-patent in 2012...

ResearchBlogging.orgAlvarez E, Perez V, Dragheim M, Loft H, & Artigas F (2011). A double-blind, randomized, placebo-controlled, active reference study of Lu AA21004 in patients with major depressive disorder. The International Journal of Neuropsychopharmacology , 1-12 PMID: 21767441

Thursday, July 21, 2011

What Did Marc Hauser Do?

Marc Hauser, the cognitive psychologist who's been under scrutiny over a case of scientific misconduct since August last year (see past posts), has resigned from Harvard University.

He'd already been suspended from teaching, but until this announcement, it looked as though he might be able to hang on and resume his research, which focussed on the evolution of language and morality. Not any more. Hauser says he's quitting the field that made him famous:
“While on leave over the past year, I have begun doing some extremely interesting and rewarding work focusing on the educational needs of at-risk teenagers. I have also been offered some exciting opportunities in the private sector,” Hauser wrote in a resignation letter to the dean, dated July 7. “While I may return to teaching and research in the years to come, I look forward to focusing my energies in the coming year on these new and interesting challenges.”
So that's the end of the Hauser controversy, then?

Not really. The problem is, we still don't know what actually happened. It's hard for anyone to draw a line under this and move on, as Hauser seems to be doing.

Harvard have been reluctant to reveal any more than the barest details of the case. When the allegations first appeared, they set up an internal investigation. In August 2010 this concluded that Hauser was "soley responsible" for 8 cases of scientific misconduct.

But no-one - outside Harvard's investigative committee - knows what they were. He's been found guilty, and he's been punished, but no-one knows the crimes or the evidence against him.

Am I alone in finding this situation unsatisfactory?

Marc Hauser has published hundreds of scientific papers as well as various books. Only a small number of papers were implicated in the misconduct allegations. But to scientifically evaluate the rest of Hauser's work, we need to know what happened - and how easy the misconduct was to detect.

It makes a big difference, for example, whether the misconduct was the kind of thing that could have been going on, leaving no trace, for many years prior to this.

The lack of firm facts has led to discussion of the case being dominated by rumours and speculation. In October last year, for example, a newspaper published an article claiming that the case against Hauser might not be as strong as it first seemed.

This led to a rebuttal by Gerry Altman, then Editor of Cognition, a journal from which Hauser retracted a paper. Altman said that based on the information he had, Hauser was indeed guilty. But he admitted that he was going on what the Harvard investigation told him; he had not had access to the full data.

When Harvard found Hauser guilty, the Dean of his Faculty justified their secrecy:
The work of the investigating committee as well as its final report are considered confidential to protect both the individuals who made the allegations and those who assisted in the investigation.

Our investigative process will not succeed if individuals do not have complete confidence that their identities can be protected throughout the process and after the findings are reported to the appropriate agencies.

Furthermore, when the allegations concern research involving federal funding, funding agency regulations govern our processes ... For example, federal regulations impose an ongoing obligation to protect the identities of those who provided assistance to the investigation.
However, while this is certainly important, I don't see why it would prevent Harvard from releasing the conclusions of the report. They don't need to name the people who gave evidence against Hauser - but they do need to spell out what he did, and what they think he didn't do, so that the scientific community can come to their own conclusions as to the validity of the rest of Hauser's work.

In his letter, the Dean closed by saying that Harvard were going to
form a faculty committee this fall to reaffirm or recommend changes to the communication and confidentiality practices associated with the conclusion of cases involving allegations of professional misconduct.
I hope so.

Wednesday, July 20, 2011

Blindsight and Consciousness In The Brain

A new paper claims to show the neural activity associated with consciously seeing something:
You might think it would be easy to find the neural correlates of seeing stuff. Just pop someone in the scanner and show them a picture.

However, it's not that simple, because that wouldn't tell you which brain activations were associated with concious awareness as such, as opposed to all of the other things that happen when we see a picture, many of which may be unconscious.

The new paper makes use of a patient, "GY", who has what's known as blindsight, a mysterious phenomenon caused by damage to the primary visual cortex on one side of the brain. In GY's case this was caused by head trauma at age 8. He's now 52, and is unable to see anything on the right side of his visual field. He only sees half the world.

However, he is still able to respond to some kinds of visual stimuli on the right, as if he could see them. But he reports that he doesn't. Blindsight is a rare phenomenon but one that's been extensively studied, because of its obvious scientific and indeed philosophical interest.

In this study the authors used fMRI to try to work out the neural correlates of concious awareness as opposed to unconcious responses. They showed GY a set of horizontal and vertical bars. His task was to say whether the horizontal bars were on top or not.

The stimuli were shown on either the left or the right. The trick was that they set it up such that it was equally easy in either the "good" or the "blind" side of the brain. In order to do that, they had to make the contrast of the bars much less bright on the "good" side.

What happened? As expected, behavioural performace was equal whether the stimuli were on the left or the right. GY got the judgement right about 75% of the time.

However, his brain responded much more strongly to stimuli on the good side - stimuli that were consciously perceived. Activations appeared all over the cerebral cortex in the occipital, parietal and frontal lobes, as you can see in the pic at the top.

The only area more activated by the unconscious stimuli was a tiny blob in the amygdala.

So what does this show? Is it "the neural correlates of conscious awareness", that Holy Grail of neuro-philosophers?

Maybe. It's a clever experimental design, which rules out some alternative explanations. It's hard to argue that the conciously perceived stimuli were just stronger, and hence more likely to affect the brain. They were actually much fainter.

And it's hard to argue that this represents subconscious information processing, or the process of making the decision whether the horizontal bars were top or bottom, because that was also going on in the blind condition and performance was the same.

Yet my concern is that the main route by which visual information gets into the cortex from the eyes, is via V1, the part which was damaged on one side. So in a sense it's no surprise at all that the cortex was more activated in the conscious condition.

Maybe this is the whole point - maybe this study shows us that consciousness is to do with cortical processing. However, when you put it like that, it seems a bit of an anticlimax. I don't think anyone would seriously dispute that. The cortex does almost everything. The interesting debates are about where in the cortex consciousness happens, if indeed it's localized at all, and what kind of processing underlies it.

It's unlikely that all of the activated areas were directly linked to conscious awareness. But we don't know which of them were.

ResearchBlogging.orgPersaud, N., Davidson, M., Maniscalco, B., Mobbs, D., Passingham, R., Cowey, A., & Lau, H. (2011). Awareness-related activity in prefrontal and parietal cortices in blindsight reflects more than superior visual performance NeuroImage DOI: 10.1016/j.neuroimage.2011.06.081

Sunday, July 17, 2011

Your Drug Treatment Center Maryland

treatment centers in Maryland that many individuals are losing their lives to what many call a disease of mass proportions. If the individuals that are taking different types of drugs are also using alcohol and other forms of downers to get their fix, many times this problem gets so bad that they resort to holdups and purse snatchings then move on to some bigger situations because their drug habit becomes so expensive that they cannot supply it with petty thievery.

If this sounds like someone you know then Drug Treatment Center Maryland will work with you on some of the needs that are specific to the type of drug they are using. Say for instance, you have a alcohol problem, then your focus should be facilities that specialize in alcohol drug treatment in Maryland as their priority. Several people do not think they have a problem when they are first approached by friends and family. But most of the time at that point they are not that far gone and could use some help and enter treatment immediately before it gets progressively worse.

There are also counselors available that will work with the entire family to help cure you of the use of these poisonous and deadly drugs in any way they can. If you are a family member of one of these drug users than you might want to log onto the Internet and get some information about drug treatment in Maryland and ways to go about getting some help for the one you love that is struggling. Some of the institutions that treat this type of disease will use other drugs like buprenorphine to combat the withdrawal symptoms with medication that will ease the pain.

So what is buprenorphine and how does it work? Basically, it is an opiate medication that is used for the treatment of addiction. The evolution of knowledge regarding different treatment methods and medications that are used to assist with withdrawal symptoms is progressive but many people remain unaware that there are such medications for this reason and try to kick the habit by themselves and it just does not work.

Now, there are many doctors who specialize in drug treatment in Maryland and have the experience to diagnose and treat your problem with the utmost care and concern for you as an individual. Making this situation more stressful only adds to the problem itself, and as we all know we are trying to remedy the problem not make it worse. Either using the chemical way to rid yourself of these drugs or the psychological way using a professional drug treatment centers Maryland will be your best bet overall.

Friday, July 15, 2011

Violent Brains In The Supreme Court

Back in June, the U.S. Supreme Court ruled that a Californian law banning the sale of violent videogames to children was unconstitutional because it violated the right to free speech.

However, the ruling wasn't unanimous. Justice Stephen Breyer filed a dissenting opinion. Unfortunately, it contains a whopping misuse of neuroscience. The ruling is here. Thanks to the Law & Neuroscience Blog for noticing this.

Breyer says (on page 13 of his bit)
Cutting-edge neuroscience has shown that “virtual violence in video game playing results in those neural patterns that are considered characteristic for aggressive cognition and behavior.”
He then cites this fMRI study from 2006. It's from the same group as this one I wrote about recently.

Breyer quotes this study as part of a discussion of the evidence linking violent video game use to violence. I have nothing to say about this, but I will point out than the fact that violent crime fell heavily in America after 1990, which is when the Super Nintendo and Sega Megadrive were invented.

Anyway, does this study show that playing violent games causes aggressive brain activity? Not exactly. By which I mean "no".

They scanned 13 young men playing a shooter game. The main finding was that during "violent" moments of the game, activity in the rostral ACC and the amygdala activity falls. At least this is the interpretation the authors give.

OK, but even if this neural response is "characteristic for aggressive cognition and behavior", it only lasted a few seconds. There's no evidence at all that this causes any lasting effects on brain function, or behaviour.

The real problem though is that the whole thing is based on the theory that violence is associated with reduced amygdala (and rACC) activity.

The authors cite various studies to this effect, but they don't distinguish between reduced activity as an immediate neural response to violence, as in this study, and reduced activity in people with high exposure to violent media, in response to non-violent stimuli.

This is rather like saying that because having a haircut reduces your total hair, and because bald people have no hair, haircuts cause baldness. Short-term doesn't automatically become long-term.

Besides, the whole idea that amygdala deactivation = violence is a bit weird because they used to destroy people's amydalas to reduce violent aggression in severe mental and neurological illness:
Different surgical approaches have involved various stereotactic devices and modalities for amygdaloid nucleus destruction, such as the injection of alcohol, oil, kaolin, or wax; cryoprobe lesioning; mechanical destruction; diathermy loop; and radiofrequency lesioning...
Lovely. It even worked sometimes, apparantly. Although it killed 4% of people. You can't reduce the activity of a region much more than by destroying it, yet destroying the amygdala reduced violence, or at the very least, didn't make it worse.

The truth is that aggression isn't a single thing. Everyone knows that there are two main kinds, "in cold blood" and "in the heat of the moment". Killing someone in a spontaneous bar brawl is one thing, but carefully planning to sneak up behind them and stab them is quite another.

Just based on what we know about the rare cases of amygdala-less people, I would imagine that destroying the amygdala would reduce violence "in the heat of the moment", which is motivated by anger and fear. The kind of patients who got this surgery seem to have been that kind of violent person, not the cold calculating kind.

So, even if violent video games reduced amygdala activity long term, that would probably reduce some kinds of violence.

ResearchBlogging.orgWeber, R., Ritterfeld, U., & Mathiak, K. (2006). Does Playing Violent Video Games Induce Aggression? Empirical Evidence of a Functional Magnetic Resonance Imaging Study Media Psychology, 8 (1), 39-60 DOI: 10.1207/S1532785XMEP0801_4

Thursday, July 14, 2011

New Brain Cells: Torrent, or Trickle?

An important paper just out asks, Could adult hippocampal neurogenesis be relevant for human behavior?

Neuroscientists, and the media, are very excited by hippocampal neurogenesis - the ongoing creation of new neurons in an area called the dentate gyrus of the hippocampus. This is because it was thought, for a long time, that no new neurons were created in the adult brain. It turned out that this was wrong.

There's lots of exciting suggestive evidence that the process is involved in learning and memory, responses to stress, depression, and the action of antidepressants, to name just a few, although this is controversial.

However, there's a big question which has rarely been considered: how much neurogenesis are we talking about? Are there enough new cells that it would be realistic for them to be doing important stuff, or is it just a little trickle?
The most common source of skepticism toward a functional role for adult neurogenesis is the perception that too few new neurons are added in adulthood to have a significant impact. Interestingly, this concern, while valid, is usually raised informally and rarely in the scientific literature. Very few studies have addressed this issue...
The new paper reviews the evidence. Firstly, they point out that in the hippocampus, there's a group of cells called dentate gyrus granule cells which are unusual in that activity in just a few of these cells can have big downstream consequences. And these are the cells that new born neurons turn into.
Each granule cell contacts only 10–15 CA3 pyramidal cells...a single granule cell is able to trigger firing in downstream CA3 targets...Because of this “detonator” action...a single granule neuron can potentially have a large impact despite representing only a tiny fraction of the population.
So new cells may play an important role. But exactly how many are there? They re-analyze data from their own lab in rats, and, making a few assumptions, arrive at the following rough estimate: in 3 month old rats, there are 650k "young" cells less than 8 weeks old; even in 2 year old rats (ancient, for a rat) there are 50k.

This is enough to have a big impact downstream:
Since there are approximately 500,000 CA3 pyramidal cells, and each granule cell contacts 11–15 pyramidal cells, this suggests that even in the oldest animals, each CA3 pyramidal cell could receive a direct contact from a young granule cell
That's all in rats, though. What about humans? It's hard to tell. The problem is that the best way to assess the rate of neurogenesis is to inject a drug called BrdU and then study the brain post-mortem. Unfortunately, this drug can cause cancer so you can't just give it to people for the purposes of science. The only time it's used in humans is (ironically) to help detect cancer.

However, one study did manage to look at BrdU staining in the hippocampus, using people who'd been injected with BrdU for cancer (not brain cancer) and then died. This study found, the authors say, rates of neurogeneis at least as high as in rats, considering the low dose of BrdU, the fact that the patients were old, and stressed (by having cancer).

They admit that this is just one study, and comparing doses between rats and humans is inexact. They nonetheless conclude:
Are these numbers potentially sufficient to exert a functional impact in humans? We feel that the answer to this question is an overwhelming "yes".
ResearchBlogging.orgSnyder JS, & Cameron HA (2011). Could adult hippocampal neurogenesis be relevant for human behavior? Behavioural brain research PMID: 21736900

Wednesday, July 13, 2011

The Brain Is Not Made of DNA

A new paper claims to have found A novel functional brain imaging endophenotype of autism.
They used fMRI to show that the brains of teenagers with autism showed no activation differences to looking at smiling happy faces, or afraid faces, compared to unemotional ones. In teens without autism, there was strong activation in many emotional and face-related brain regions. The unaffected brothers and sisters of the autistic people showed intermediate effects.

This is a fine study. The finding that siblings of people with autism have weakened neural responses to emotional faces is quite important as it suggests that this finding correlates (to some degree) with your position on the autism "spectrum".

The abstract of the paper actually downplays this, and says "The response in unaffected siblings did not differ significantly from the response in autism". However, there was a significant linear trend of group, and looking at the graphs, it's clear the siblings were In The Middle, like Malcolm.

There's plenty more nice things you could do with these results, which is an unusally large and rich dataset (120 people - 40 in each group). You could see, for example, whether siblings tend to be similar in terms of neural response. You could see whether the siblings who are most alike in brain response, are closest in symptoms. Or just look a the structural data on brain size and shape to see if there are characteristic differences between siblings that make one of the autistic and the other not.

There are a few problems. Most of the analyses are subject to the non-independence problem, because they defined their regions of interest based on the areas that showed a significant happy vs neutral face effect in the control group. So it's no surprise that when they generated graphs from these areas, the control group showed the strongest effect. However, they also do whole-brain analyses which avoid this problem and I don't think it undermines the main results.

So it's a decent study. But is this a "biomarker", or "endophenotype", as the title of the paper has it?

These are both hot topics in neuroscience at the moment. As the authors put it (emphasis mine):
An endophenotype is a heritable feature associated with a condition, present in affected individuals regardless of whether their condition is manifested, which co-segregates with the condition in families and which is present in unaffected family members at a higher rate than in the general population.

In such family members, endophenotypes represent instances in which genes associated with a particular condition exert measurable effects in individuals in whom they are insufficient to cause the condition itself...

The promise of characterizing endophenotypes lies in their hypothesized intermediate position between genotype and phenotype... the etiology of the endophenotype is likely to be correspondingly simpler: it can be said to be ‘closer to the level of gene action’.
The idea, in other words, is that if we can find a difference in the brains of people with autism, and their unaffected relatives who (presumably) share some of the same genes, we might have found a mechanism by which the genes ultimately cause the symptoms.

It might be easier, then, to find the genes for brain-not-lighting-up-to-happy-faces, than it will be to find genes for autism. Then once we've found those, we can use them to better understand autism.

My concern is that, while in theory endophenotypes seem "closer to the genetics" because they're "biological" rather than "behavioural", this is just a philosophical illusion based on the idea that the mind is not the brain.

We actually have no idea whether brain-not-lighting-up-to-happy-faces is closer to genetics than autistic behaviour. I'd say that our default assumption should be that everything is exactly the same "distance" from DNA, that is to say, everything is the product of complex interactions between genes and environment.

Some things are under the more or less exclusive control of a small number of genes, and these are called "genetic", but it's important not to assume that just because something's "in the brain", it's probably "more genetic" in this sense. The brain is a product of the environment as well.

If you scanned my brain while playing an audio recording of Urda love poetry, not much would happen. I don't know Urdu. In someone who did speak Urdu, all kinds of language and emotional areas would light up. That doesn't mean Urdu-brain-response is genetic. It's exactly as genetic as speaking-Urdu, which isn't genetic.

ResearchBlogging.orgSpencer, M., Holt, R., Chura, L., Suckling, J., Calder, A., Bullmore, E., & Baron-Cohen, S. (2011). A novel functional brain imaging endophenotype of autism: the neural response to facial expression of emotion Translational Psychiatry, 1 (7) DOI: 10.1038/tp.2011.18

Sunday, July 10, 2011

Drug Abuse - A Real Problem

Drug abuse is certainly one of the problems of the state of Colorado. This problem doesn't affect one specific group, race, or socio-economic component. It has affected almost every family in America. Many of these people go on to get arrested and moved through the states penal system. As of 2002, 61.7% of males arrested in Denver tested positive for drug use.

Drug abuse is seen when an individual becomes chronic or a regular drug user. In this case, a physical dependency on the drug is developed. Abuse of drugs usually starts during an individual's adolescent years. On average, this is around the age of 12 since taking drugs has become a common social activity for many in society. Because of this, more ranges of people find themselves facing addiction.

With the growing concern of drug abuse in the state, more employers are conducting drug testing. Hiring employees with drug problems can cause many concerns for a business. There is also liability on behalf of the company involved with this issue. Drug testing firms are hired to provide data that shows if a potential employee is a drug user. Here are some problems seen from drug abuse in the workplace:

Erratic Behavior

Drug abuse can cause the addict to start acting weird under the influence. This will depend on the type of drug being used. Erratic behavior is connected to drugs like heroin, opium, and cocaine. Heroin and cocaine account for much of the state's drug use. The Denver area especially has become the largest source of drugs for most addicts.

Loss of Productivity

Some people indulging in drug abuse are able to hide their problems. These are the limited few who can perform work tasks despite their condition. Others, however, are not competent enough to do their jobs. As a result, they may either mess whatever tasks they're handling or cost the company a large sum of money.

Drug abuse has found its way into most families in this country, and it continues to do so until some action is taken against it. However, with the popularity of drug testing, maybe addicts will become motivated enough to leave this habit once and for all.

Saturday, July 9, 2011

Depression: From Treatment to Diagnosis?

In theory, medicine works like this. You get some signs or symptoms. You go to the doctor, and depending on those, you get a diagnosis. Your doctor decides on the best available treatment on that basis.

The logic of this system depends upon the sequence. A diagnosis is meant to be an objective statement about the nature of your illness; treatments (if any) come afterwards. It would be odd if the treatments on offer influenced what diagnosis you got.

An interesting paper just out suggests that exactly this kind of reverse influence has happened. The authors looked at what happened in the USA in 2003 when antidepressants were slapped with a "black box" warning, cautioning against their use in children and adolescents, due to concerns over suicide in young people.

They used the data from the annual National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS). These record data on the number of patients visiting their doctor regarding different illnesses, and what medications were prescribed if any.

What happened? The warning led to a reduction in the use of antidepressants. No surprise there, but unexpectedly, this wasn't because teens who visited their doctor regarding depression, were less likely to get given these drugs.

Actually, the proportion of depression visits, that were also antidepressant visits, was almost unchanged:
The proportion of depression visits with an antidepressant prescribed, having risen from 54% in 1998–1999 to 66% in 2002–2003, remained stable in 2004–2005 (65%) and in 2006–2007 (64%)
The difference was caused by a reduction in the number of teens getting diagnosed with depression - or rather, the number of visits where depression was mentioned; we can't tell if this meant doctors were less likely to diagnose, or patients were less likely to complain, or whatever.

This graph shows the story. After 2003, both antidepressant visits and depression visits fall, while the proportion of "antidepressant & depression" visits to the total depression visits (purple line), is constant.

The effect seen is just a correlation - it might have been a coincidence that all this happened after the black box warning in 2003. It seems very likely to be causal, though. Antidepressant use was rising steadily up until that point - and in adults, both depression and antidepressant visits rose after 2003.

It's also dangerous to pile too many heavy conclusions on the back of one study. But having said that -

Getting diagnosed with depression - at least if you're a teenager in the USA - is not just a function of having certain symptoms. The treatments on offer are a factor in determining whether you're diagnosed.

One alternative view, is that the fall in depression visits represents the fact that kids on antidepressants tend to have multiple visits - in order to monitor their progress, adjust dosage etc. So when antidepressant use fell, the number of visits fell. But if it were true, we'd presumably expect to see a fall in the proportion of visits that dealt with antidepressants, which we didn't.

This is disturbing either way you look at it. If you think the pre-2003 diagnoses were appropriate, then after 2003, kids must have been going undiagnosed with depression. On the other hand, if you think post-2003 was a welcome move away from over-diagnosis of depression, then pre-2003 must have been bad.

As to what happened to the kids who would have got a diagnosis of depression post-2003 were it not for the black box warning, we've got no way of knowing.

Why did this happen? Psychologist Abraham Maslow famously said "It's tempting, if the only tool you have is a hammer, to treat everything as if it were a nail." The history of psychiatry bears this out.

Sigmund Freud's psychoanalysis was essentially the theory that most mental disturbance was a 'neurosis' or 'complex' of the kind that's best treated by lying on a coach and talking about your dreams and your childhood, which as luck would have it, was exactly what Freud had just invented.

Along came psychiatric drugs, and suddenly everything was a 'chemical imbalance'. I've previously suggested that the invention of SSRI antidepressants, in particular, may have changed the concept of depression into one which was most amenable to treatment with SSRIs.

Recently, we're seeing the rise of the view that everything from psychosis to paedophilia is about 'cognitive biases' that can be treated by the latest treatment paradigm, CBT.

We always think we've hit the nail on the head.

ResearchBlogging.orgChen SY, & Toh S (2011). National trends in prescribing antidepressants before and after an FDA advisory on suicidality risk in youths. Psychiatric services (Washington, D.C.), 62 (7), 727-33 PMID: 21724784

Wednesday, July 6, 2011

The Partly Asleep Brain

Some animals - such as dolphins and whales - are able to "sleep with half their brain". One side of the brain goes into sleep-mode activity while the other remains awake.

But a remarkable new study has revealed that something similar may happen in humans as well - every night.

The research used a combination of scalp EEG, and electrodes planted inside the brain, to record brain activity from 5 people undergoing surgery to help cure severe epilepsy. The subjects were then allowed to go to sleep for the night, while recording took place.

As expected, after falling asleep, the EEG showed delta wave activity - strong, slow waves of electrical activity (0.5 to 4 Hz) which are typical of deep, dreamless "slow wave sleep".

However, the electrodes inside the brain told a different story. While they recorded delta waves most of the time, they also showed that there were episodes, lasting from a few seconds to up to 2 minutes, in which the motor cortex suddenly went into "waking mode". Delta waves disappeared, and were replaced with fast, unpredictable activity.

This image shows one episode, lasting just 5 seconds. The hotter the color, the more activity in a particular frequency. The higher the band, the higher the frequency. This shows a clear burst of high frequency activity in the motor cortex. The other parts of the brain showed the opposite effect - even stronger slow wave activity - at the same time.

Another area, the dorsolateral prefrontal cortex, also showed this phenomenon occasionally, but it was much less common than in the motor cortex.

There's a few caveats. These patients had severe epilepsy, and they were taking anti-convulsant drugs. This wouldn't obviously create the effects seen here, but we can't rule it out. Still, these results are intriguing.

They challenge the view of slow wave sleep as a "whole brain" phenomenon. We've known for a while that this isn't true of animals, and in people with certain sleep disorders, but this is first demonstration in healthy humans.

It may help to explain the mysterious fact that, although slow wave sleep is often referred to as "dreamless", there are consistent reports that people woken up from this phase of sleep do report dreaming (or at least thinking) about things.

While episodic arousal of the motor cortex probably wouldn't explain this per se, if the same thing happens in the visual cortex or other sensory areas, it might create dreams.

ResearchBlogging.orgNobili L, Ferrara M, Moroni F, De Gennaro L, Russo GL, Campus C, Cardinale F, & De Carli F (2011). Dissociated wake-like and sleep-like electro-cortical activity during sleep. NeuroImage PMID: 21718789

Autism Isn't Very Genetic...Or Is It?

The environment is more important than genetics in setting the risk for autism, according to a new study that's got the media in a tizzy.

The paper, which is free, is here: Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism

It's a twin study, and like all such research, it aims to estimate heritability, the proportion of the variability in autism risk caused by straightforward genetic effects. A heritability of 0% means no genetics and 100% means purely genetic. Note, however, that complex interactions between genes, epigenetics, and gene-environment interactions would throw the whole thing off.

Twin studies rely on the fact that there are two kinds of twins. Identical, or monozygotic (MZ), pairs have identical DNA, while dizygotic (DZ) twins are no more alike than any other brothers or sisters, genetically. So MZ twins ought to be more alike than DZ twins (have a higher "concordance"), and the size of the MZ-DZ difference is a measure of heritability.

There have been several previous twin studies of autism, and they've tended to find a heritability of around 90%, with high MZ concordance and very low DZ. However, these tended to be small and used outdated methods of diagnosis.

The new study used California records to find all twin pairs, born in the state between 1987 and 2004, where at least one of the twins had a diagnosis of autism on the DDS register of people receiving state services for developmental disorders.

They found 1156 twin pairs. Of these, they managed to recruit and get full data from 202 pairs. They gave all these 404 kids full autism diagnostic assessments. This is not a great response rate. Parents of responders tended to be slightly better educated and more likely to be white than the non-responders.

Here's the key data: concordance was higher in MZ twins, but not by nearly as much as previous studies would predict. Putting these data into a statistical model, assuming a baseline rate of autism of 1% in boys and 0.3% in girls, found that the most likely explanation was a heritability of about 35-40% and an effect of "shared environment", i.e. family factors, of 55-60%.

So. Autism's not very genetic?

Maybe. This is certainly a major study and all autism researchers need to take note. But there's some caveats.

My major concern is that the DZ concordance might be too high, because a kid might be more likely to get diagnosed with autism if their twin already had a diagnosis. Suppose you're a parent and one of your twins is diagnosed - of course you're going to worry about the other one, and start thinking, are they really so different?

Although all the people in this study were (re)assessed for study purposes, the diagnostic instruments are hardly immune to the effects of prior diagnosis. The ADI interview is based on parental report of early childhood behaviour. Parents know whether the other twin has autism. The other interview, the ADOS, is based on direct observation of the patient, so it might avoid this - but you have to score on the ADI to get a diagnosis.

This, by itself, wouldn't explain the discrepency between these data and older twin studies. But we also know that diagnoses of autism in general has skyrocketed recently. People seem to be becoming more willing to accept that diagnosis, and more aware of the symptoms. So it's quite possible that some of the "unaffected" twins from older studies would get a diagnosis today if they were to have the kind of modern, formal assessment done in this study.

This doesn't mean that the new study is wrong. If this explanation is true, then the study is quite right - there is a strong shared environmental influence on autism diagnosis. But not necessarily on autism.

One reason to suspect that this is going on - and this is purely a hunch - is that the estimates of shared environmental influence, i.e family environment, was 55%. This is exceptionally high, because almost every other human disorder or trait for which twin studies have been done, have reported low shared environmental effects, and high individual environmental effects (smoking, alcoholism, anxiety, depression). In fact people have written books about this.

Maybe autism's different. Yet I'm more willing to accept that autism diagnosis is different.

A related, but seperate, point: it's very likely that some autism is more genetic than others. In particular we know that some cases are caused by single genetic variants, and these tend to be severe with associated low IQ and sometimes other abnormalities; this is sometimes called "syndromic" autism.

It's always easier to spot a severe case than a mild one. So it's quite possible that older studies had a higher proportion of these cases, because the diagnostic system was only able to pick up those ones. Maybe in more recent times, as diagnosis has expanded, "autism" is coming to cover a "less genetic" set of things.

The good thing about these data is that they span births from 1987 to 2004. So it would be possible to check this theory by looking to see whether the early data i.e. the older twins, have a higher heritability.

Finally, Michelle Dawson pointed out on Twitter that there's another large twin study from Wisconsin, as yet unpublished but presented at a conference. They found broadly comparable results.

ResearchBlogging.orgJoachim Hallmayer, et al. (2011). Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism Archives of General Psychiatry

Tuesday, July 5, 2011

Melancholia In 100 Words

The British Journal of Psychiatry have a regular series called "In 100 Words", which produces some gems. This month they have Melanchola in 100 Words, featuring perhaps the most influential musician you haven't heard of, Robert Johnson.
I got stones in my pathway/And my road seems dark at night/I have pains in my heart/They have taken my appetite.

Robert Johnson, known as the King of the Delta blues singers, distilled into these lines the essence of severe depressive illness – somatic ills, fear and suspicion, emotional and physical pain, nocturnal troubles and struggle against obstacles. The words are one with the powerful, haunting music. ICD-10 and DSM-IV have their place, but poets have often been there before us, and done a better job. We can all learn from Robert Johnson, born just 100 years ago.
I've previously written about the blues and what shade of blue they were talking about, here. But this actually isn't the first Melancholia in 100 Words to appear in the BJP. Here's another one from 2009

Melancholia is a classical episodic depressive disorder that combines mood, psychomotor, cognitive and vegetative components with high suicide risk. In the present psychiatric classification it is buried as a modifier in both bipolar and unipolar depressions. It is hardly used to characterise patients in the clinic or research.

The syndrome is frequently recognised in delusional and agitated depression, and in the elderly. Cortisol or sleep EEG abnormalities are prognostically helpful. Melancholia is particularly responsive to tricyclic antidepressants and electroconvulsive therapy but not to selective serotonin reuptake inhibitors or psychotherapy. Recognising melancholia as a distinct disorder improves clinical care and research.