Beware Good Theories

The ancient Greeks had a lovely theory. Certain places on the earth (caves, mostly) were, they thought, gateways to the underworld. Plants growing near these places could absorb the deadly essence of Hades and became poisonous.

Snakes and other venemous creatures got their poison by consuming these plants. And stinging insects got their little doses of poison by feeding off dead snakes.

Isn't that a great narrative? It explains everything, in a nice logical progression. OK, it presupposes what we would call a "supernatural" force as the ultimate origin of poison, but other than that, it's an entirely "scientific" account. In accordance with Occam's Razor, it proposes a single unified process underlying diverse phenomena.

It is, in other words, a perfect scientific theory. It's completely wrong, on every point, but we only know that because we now understand atoms, molecules, chemistry and biochemistry, which the Greeks had no way of knowing. At the time, the Hades theory was surely the best possible theory about where poison came from.

The moral of this story is, beware nice theories based on incomplete data.


Reference: Greek Fire, Poison Arrows and Scorpion Bombs, which I'm currently reading, all about chemical and biological weapons.

Cognitive Behavioural Therapy vs. Psychoanalysis

Clinical trials of cognitive behavioural psychotherapy (CBT) for depression are often of poor quality - and are no better than trials of the rival psychodynamic school.

So says a new American Journal of Psychiatry paper that could prove controversial.

CBT is widely perceived as having a better evidence base than other therapies. The "creation myth" of CBT (at least as I was taught it) is that it was invented by a psychoanalyst who got annoyed at the unscientific nature of psychodynamic i.e. Freudian-influenced therapy. CBT has always looked on clinical trials more favorably than the dynamic school.

However, the authors of this meta-analysis found that while there are certainly lots of published CBT trials for depression, they're actually no better quality than the psychodynamic trials.

"Surprisingly" (their word), they found no difference between the CBT for depression trials, and the psychodynamic trials, on a rating score of trial methodology.

Trials got better over time, but the two groups improved equally (see above). The mean score was 25.5 for CBT and 25.1 for dynamic, on a scale that goes from 0 to 48. Anything over 24 points is deemed acceptable but this is clearly an arbitrary cut-off.

The RCTP-QRS scale is relatively new and it was developed by the people who wrote this paper (albeit with the input of other experts.) There's 24 items and each gets a score from 0 (bad) to 2 (good). Items are things like "Adaquate sample size", "Patients randomly assigned to group", etc.

Worryingly, better CBT trials tended to find smaller benefits of CBT over the comparison treatment. The overall results showed that while CBT was clearly better than doing nothing, it was pretty much the same as antidepressants, and other psychotherapies, in adults with depression:

The article follows one from the same group, Gerber et al, who reviewed the evidence for psychodynamic therapy in more detail. And last year, another team reported evidence of publication bias in psychotherapy trials. In this study, the authors report possible publication bias, but they don't go into detail.

Overall this is interesting stuff, and a reminder that while CBT has the most evidence of any psychotherapy, this is not the same thing as saying that it has the best evidence...

Nathan C. Thoma et al (2011). A Quality-Based Review of Randomized Controlled Trials of Cognitive-Behavioral Therapy for Depression: An Assessment and Metaregression American Journal of Psychiatry

David & The Law of One

Here is an odd synchronicity.

Just as I was struggling with something in my personal life that has to do with forgiveness, I logged onto David Wilcock's website - Divine Cosmos. It just so happens I am in the middle of reading his new book The Source Field Investigations. But I am also in the middle of reading book one of The Law of One.

David just posted a 20-minute video pertaining to The Law of One, which was written in 1984. What are the odds?

Anyway, he talks about personal spirituality, divination through Tarot Cards, and the ultimate responsibility of humans on earth at this time - which is?


Forgiveness.

This supposedly frees us from the wheel of karma and reincarnation, by letting go of the guilt of the past, along with the fear of the future.

Our old traumas, usually early childhood traumas, are the hardest to work through, but give us the best chance of freedom from repetition. Once you have made a commitment to forgive the people who may have hurt you, even inadvertently, you can then remind yourself that you have already forgiven that person when a negative thought or emotion comes along to replay your hurt/anger/resentment, etc.


Negativity bias is when the brain automatically returns to a negative thought five times more often then a positive one. The only way to change that thought is to replace it with positive thoughts. In the case of forgiveness one can say - sorry - can't go there - I've already forgiven that person and myself and anyone else involved - time to move on.

I guess I was meant to hear this information tonight - just after a long-winded rant today on the very person I need to forgive.

You never know where the information you need might come from. I'm not sure that everything David talks about on his website is part of my own personal cosmology - but taking the information you need, when you need it, is part of trusting the Creator. Whether is is from a writer/website or a billboard on the side of the road - when you are open to synchronicity, you find magic.

Here is his video - maybe you were meant to drop by my blog for a reason...

Beware Dead Fish Statistics

An editorial in the Journal of Physiology offers some important notes on statistics.

But even more importantly, it refers to a certain blog in the process:

The Student’s t-test merely quantifies the ‘Lack of support’ for no effect. It is left to the user of the test to decide how convincing this lack might be. A further difficulty is evident in the repeated samples we show in Figure 2: one of those samples was quite improbable because the P-value was 0.03, which suggests a substantial lack of support, but that’s chance for you! A parody of this effect of multiple sampling, taken to extremes, can be found at http://neuroskeptic.blogspot.com/2009/09/fmri-gets-slap-in-face-with-dead-fish.html

This makes it the second academic paper to refer to this blog as far. Although I feel rather bad about this one, since the citation ought to have been to the original dead salmon brain scanning study by Craig Bennett. I just wrote about it.

Actually, though, this editorial was published in five separate journals: The Journal of Physiology, Experimental Physiology, the British Journal of Pharmacology, Advances in Physiology Education, Microcirculation, and Clinical and Experimental Pharmacology and Physiology. Phew.

In fact, you could say that this makes not two but six citations for Neuroskeptic now. Yes. Let's go with that.

Anyway, after discussing the history of the ubiquitous Student's t-test - which was invented in a brewery - it reminds us that the p value you get from such a t-test doesn't tell you how likely it is that your results are "real".

Rather, it tells you how often you'd get the result you did, if there was no effect and it was just random chance. That's a big difference. A p value of 0.01 doesn't mean your results are 99% likely to be real. It means that there's a 1% chance that you'd get them, by chance. But if you did say 100 experiments, or more likely, 100 statistical tests on the same data, then you'd expect to get at least one result with a p value of 0.01 purely by chance.

In that case it would be silly to think that the finding was only 1% likely to be a fluke. Of course it could be true. But we'd have no particular reason to think so until we get some more data.

This is what the dead salmon study was all about. This multiple comparisons issue is very old, but very important. Arguably the biggest problem in science today is that we're doing too many comparisons and only reporting the significant ones.

Drummond GB, & Tom BD (2011). Statistics, probability, significance, likelihood: words mean what we define them to mean. British journal of pharmacology, 164 (6), 1573-6 PMID: 22022804

Marriage in Australia: It's Time

Here's a fantastic new ad from GetUp Action for Australia in support of marriage equality. Next week, Australia's Labor Party will decide their stance on the issue. To sign the petition, click here. 

We're Making A Difference!

I've been getting updates on the petitions I've been signing. There is no doubt we're making a difference! Sometimes we look at these things and think - there is no way I, personally, can make any difference in this world. And maybe one person cannot make a difference with all of the atrocities - such as the dolphin massacre in Japan - but together, we can.

People are joining organizations all over the world. We are starting to organize in ways that is getting the attention of the powers that be. When hundreds of thousands, or millions, of signatures - complete with personal notes, show up on the desk of someone making the decision of whether or not to allow those boats out into the cove to kill dolphins - they know that what they are doing is getting world-wide attention. It is no longer a secret. 

Random acts of caring is how we will change the world. By banding together and sending a message to the people who think they are acting in vacuum - we know who you are and we want this activity to stop. We are from all nations from around the world, and we are unified.


That is our message.

Care2 Petion Site - 17,000,000 and growing!
Avaaz.org - 10,000,000 and growing!
Oceana

Do you have one to add? Send me the link and I'll add it here!

A Dangerous Truth about Antidepressants

An opinion piece by veteran psychiatrist and antidepressant drug researcher Sheldon Preskorn contains a remarkable historical note -

“A dangerous idea!” That was the response after a presentation I gave to a small group of academic leaders with an interest in psychopharmacology [over 15 years ago].

What evoked such a response? The acknowledgment that most currently available antidepressants specifically treat only one out of four patients with major depression based on the bulk of clinical trials data.

There was no argument about the accuracy of this statement, but...some claim it is “dangerous” to admit that the specific response rate to most antidepressants is 20%–30% because such an acknowledgment might undermine the value of antidepressant treatment.

By the "specific" response rate Preskorn means the number of depressed people who'll get better on antidepressants and who wouldn't have done so well on placebo. This rate is fairly low because, while most people get better on antidepressants, most of those improve on placebo as well.

Preskorn rejects the view that it's dangerous to acknowledge this:

...there are several problems with this reaction. First, it is hard to deny reality. The “placebo” response rate in antidepressant trials is arguably the most reproducible finding in psychiatry. Moreover, if available antidepressants were magic bullets, then polypharmacy would not be so common. Second, this reaction ignores the fact that antidepressants are tremendously valuable to the patients who specifically benefit from them...

Every treatment in every area of medicine has limitations. Acknowledging that fact should galvanize us to action. Denial on the other hand perpetuates the status quo.

Unfortunately, we're not told who these academic leaders were. I wonder if they included amongst their ranks some of the "key opinion leaders" in the field whose leadership proved rather less than ideal. The column is actually adapted from a 1996 article by Preskorn.

Preskorn is right, of course, that denying the fact that antidepressants are only substantially better than placebo in a fraction of people who get diagnosed with "depression" is wrong, and also misses the point: because hundreds of millions of Americans have diagnosable depression (due to the loose definition of "depression"), even if they only helped 1% of them, they'd still help over a million people.

But he doesn't mention that this approach was ultimately self-defeating. As a result of the failure to acknowledge that antidepressants are only helpful in some cases of depression (namely "severe" depression), these drugs became very widely used and - oh dear - people started saying that the drugs are being overused, and don't work in most people who take them.

Whoever could have seen that coming.

This has "devalued" antidepressants - and psychiatry itself - more than anything else has.

Preskorn SH (2011). What Do the Terms "Drug-Specific Response/Remission Rate" and "Placebo" Really Mean? Journal of psychiatric practice, 17 (6), 420-424 PMID: 22108399

The Gene That's "For" Nothing

Scientists like to warn you not to talk about "the gene for" a particular disease or trait.

I've done so in previous posts e.g. this one or this one.

But such scalding is not always very effective. We like simple explanations, so we like to find simple connections between genes and phenotypes.

Which is why a new paper is important. The authors, a large Turkish-American collaboration, found that mutations in a gene, WDR62, are associated with severe brain malformations in 9 patients. But what's interesting is that it doesn't cause any particular malformation.

If you have two faulty copies of this gene, your brain won't be normal, but what goes wrong varies widely amongst different people. Although the 9 cases had some features in common, such as microcephaly (small head and brain), in other respects they differed greatly.

As the authors put it, mutations in WDR62 cause

a wide spectrum of severe cerebral cortical malformations including microcephaly, pachygyria with cortical thickening as well as hypoplasia of the corpus callosum. Some patients... had evidence of additional abnormalities including lissencephaly, schizencephaly, polymicrogyria and, in one instance, cerebellar hypoplasia, all traits traditionally regarded as distinct entities.

These are distinct entities, in the sense that you can have any one of them, without having the others. And they are different brain changes. What the authors mean is that everyone assumed that, because they're  different, they must have different genetic causes. They've just shown that this is wrong.

So what is WDR62 "for"? Experiments in mice showed it to be involved in the migration of new neurons from their origin to their final location in the brain. So it's "for" correct neuronal placement, although how it works remains unclear.

WDR62 ought to remind us that there's a long and winding road from gene to phenotype, and that the same gene can, when mutated, cause very different symptoms. This is especially interesting in the light of recent evidence showing that the same mutations can cause a range of behavioural disorders from autism to ADHD to schizophrenia.

Bilgüvar K, et al (2010). Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations. Nature, 467 (7312), 207-10 PMID: 20729831

The Revolution is Love

I'm having a great time drinking lemongrass-ginger frosts and soaking up the sun, but came across the trailer for a new movie that is actually a movement, so I thought I would pass it along. I'm hoping to catch up with all of you next week, and hope all is well in your neck of the woods.

My heart goes out to the young people, all over the world, who are willing to put themselves on the line to bring about world-wide change. We can only hope the violence in Cairo will stop, and the police in the US will quit pepper spraying our children.

Was Evita Lobotomized?

Eva Peron, or Evita, is perhaps the most famous woman in Latin American history. As the wife of Argentinian leader Juan Peron she was immensely popular. But she died at the age of just 33 from cervical cancer, after a two year struggle with the disease.

A new paper makes the startling claim that Eva Peron may have received a prefrontal lobotomy in the months before her death. The lobotomy is best known as a treatment for mental disorders such as schizophrenia, but according to Nijensohn et al, Peron was given the operation as a kind of pain relief.

The claim was first made in 2005 by Dr George Udvarhelyi, who worked as a neurosurgeon in Argentina before moving to John Hopkins in Baltimore. After his retirement, Udvarhelyi told the Baltimore Sun that he'd performed the operation.

The authors of this paper checked out the claims against his unpublished memoirs. It turns out that they've just written Udvarhelyi's biography, and managed to slip in a plug for their book. Indeed, this paper could be seen as a plug. But anyway.

The early 1950s were the golden age of lobotomy and it does seem plausible that if she had one, it would have been kept secret. But it seems that the only direct evidence is Udvarhelyi's testimony. The authors point to various facts that could be seen as consistent with it, like this memoir by a close friend:

“The illness continued to advance. I visited her one afternoon andwas shown a notebook belonging to her brother Juancito. There was a drawing of Evita with her head criss-crossed by scissors. The sinister image suggested that she was either crazy or brain damaged. I found her very thin, quiet, and deeply introverted”

But to be honest this is pretty weak. The authors also admit that in interviews with scholarly experts on Peron's illness, they were all surprised by the idea.

They then point to postmortem X-rays of Peron's skull which were made public in 1955 to prove that her corpse hadn't been burned (long story). These, they suggest, show evidence of the kind of burr holes that were used to insert the lobotomy tools -

And they say that a photo of her shortly before her death shows an "indentation at the coronal level" -

Hmm. Not sure what to make of those. Ultimately though, the authors admit that the only way to know for sure would be to exhume Evita and study her skull, but this is unlikely to happen any time soon.

Nijensohn DE, Savastano LE, Kaplan AD, & Laws ER Jr (2011). New Evidence of Prefrontal Lobotomy in the Last Months of the Illness of Eva Perón. World neurosurgery PMID: 22079825

Fire!

Nothing like leaving home to go on vacation and then learn that your city is on fire. I don't know if we are lucky or not to be 2,000 miles away from our home this week. We've been in constant contact with our house sitters on whether or not they will need to evacuate. Over 25 homes have burned in Reno over the last two days.

A strange fire. It has moved all over the place, picking out homes in very odd places, not just the ones close to where it started. High winds have made it difficult for fire fighters to get it under control. My heart goes out to all of those that were somehow the recipients of this fickle monster.

It's funny, but when you try to tell someone what they need to save - it really isn't much. I mean, we have a whole house full of stuff, but nothing of real value. The valuable stuff is already out of the house, I guess. When you get right down to it, the only thing that really matters are the living. So now that Lucy is safe, we can enjoy our view:

Potential Personal Genomics

A while ago I wrote about how new findings in genetics could herald a new kind of "eugenics", based not around selective breeding to ensure that "bad" genes aren't passed on, but rather based on using fetal genetic testing to choose which variants enter the gene pool in the first place.

I said-

In the near future, we might be able to routinely sequence the genome of any unborn child shortly after conception

But I didn't realize that this may be really very near indeed. Two recent reports have shown that it's possible to sequence fetal DNA from a maternal blood sample. In one case it was used to diagnose a 35 week fetus with a genetic deletion on chromosome 12 seemingly associated with autism, developmental delay and shortness.

In this case it was inherited from the father (which is why they decided to test for it), but this approach could equally be used to screen for the de novo mutations that account for much disease, as I discussed in the last post.

This is big. Currently, the main way to get fetal DNA is through amniocentesis, i.e. inserting a needle into the womb. It's a substantial and not entirely safe medical procedure. A blood sample would be an order of magnitude cheaper and safer, but most of all it would be something you could do at home.

No longer would you need to go to a hospital and discuss everything with a doctor. You could take some blood, send it off anonymously to a sequencing company, and get the results in an email. It would take it out of the hands of professionals and open up a space for individual choice.

The cost of whole-genome sequencing has been falling exponentially and many think it will fall below the $1000 mark within a few years. Combine that with fetal DNA testing and we might see moderately well-off parents able to sequence fetal DNA within the next decade.


When this happens I think the personal genomics industry will suddenly become extremely "hot". At the moment you can sequence your own DNA for a few thousand $ if you want. The results may be interesting but they're of little obvious use. Whatever your genes are, you're stuck with them.

But as soon as we're talking about potential human genomes, it'll kick things up a notch. Media interest and political controversy is sure to follow. Personally I think it'll the debate will begin in earnest when we start seeing selective abortions on the basis of genes for "normal" variants rather than "disease" genes.

It's one thing to not want a child with blindness, or a high risk of leukaemia. But as a society I don't think we're ready for not wanting a child because they're predicted to be a B student rather than an A student, or brunette rather than blonde. At some point soon, though, we'll have to decide what we think about that.

Peters D, Chu T, Yatsenko SA, Hendrix N, Hogge WA, Surti U, Bunce K, Dunkel M, Shaw P & Rajkovic A (2011). Noninvasive prenatal diagnosis of a fetal microdeletion syndrome. The New England journal of medicine, 365 (19), 1847-8 PMID: 22070496

Srebniak M, Boter M, Oudesluijs G, Joosten M, Govaerts L, Van Opstal D, & Galjaard RJ (2011). Application of SNP array for rapid prenatal diagnosis: implementation, genetic counselling and diagnostic flow. European journal of human genetics : EJHG, 19 (12), 1230-7 PMID: 21694736

Does MRI Make You Happy?

A startling new paper from Tehran claims Antidepressant effects of magnetic resonance imaging-based stimulation on major depressive disorder.

Yes, this study says that having an MRI scan has a powerful antidepressant effect.

They took 51 depressed patients, and gave them all either an MRI scan or a placebo sham scan. The sham was a "scan" in a decommissioned scanner. The magnet was off but they played recorded scannerish sounds to make it believable. Patients were blinded to group.

They found that people in the scanner group improved much more than those in the sham group over two weeks. Actually there were two different kinds of scans, T1 structural MRI and EPI functional MRI, but they were the same:

Now, if this is true, it's huge. Obviously. For one thing, it would undermine the whole premise of functional MRI, which is that it's a method of recording brain activity. If it's also stimulating the brain in some way at the same time, then it would make it hard to interpret those activations. In particular it would cast all the studies using fMRI in depression into doubt.

So is it true? I can't see any obvious flaws in the design. Assuming that the authors are right when they say that "patients could not distinguish the difference between the actual and sham MRI scan", i.e. assuming that the blind was truly blind, then the methodology was sound.

But let's look at the statistics. The paper is full of very impressive p values less than 0.001 but those turn out to all be referring to the changes within each group, and those changes are fairly meaningless. What matters is the differences in the groups and

Changes in BDI scores (between baseline and day 14) were significantly different among the three studied groups (F=5.48, p=0.007 overall) using ANOVA, and between the DWI group vs. Sham and T1 vs. Sham (p<0.05) using post hoc tests. Changes in HAMD24 scores (between baseline and day 14) were also compared among the 3 groups using ANOVA but the level of significance was slightly above the significance threshold (F=2.89, p=0.06).

Which is rather less convincing. There was a close-to-significant group difference in the HAMD24, and a significant but only just effect on the BDI. Remember that there were only 17 people in each group.

I'm inclined to think that this is one of the 5% of experiments which will produce a nominally significant result even assuming everything goes to plan and there are no confounds. My suspicion is that everyone in the trial got better (they were all on antidepressants, plus there's the placebo effect and the effect of time) - except a small number of people who didn't improve. And by chance they were all in the sham group.

The reason I'm skeptical is that I just can't see a plausible mechanism. The authors suggest that MRI scans might stimulate the brain in a similar way to TMS and that this could have antidepressant effects.

But there's a lot of problems with this: 1) the evidence is questionable whether TMS even works for depression 2) the magnetic stimulation of the brain generated during MRI is much weaker than in the case of TMS and 3) if MRI really stimulated the brain like TMS, then, like TMS, it would have a risk of triggering seizures in people with epilepsy. But it doesn't.

Vaziri-Bozorg SM, et al (2011). Antidepressant effects of magnetic resonance imaging-based stimulation on major depressive disorder: a double-blind randomized clinical trial. Brain imaging and behavior PMID: 22069111

One in Four Revisited

In a recent Telegraph article, professional contrarian Brendan O'Neill argues against the idea that one in four people experience mental illness - and indeed against the idea that one in four people are bullied, abused or whatever else:

Can it really be true that a quarter of Brits are bullied or beaten up at home or are mentally ill, or is this simply a case of social campaigners exaggerating how bad life is in order that they can continue to make headlines, make an impact, and get funding? I reckon it's the latter. Next time you see the "one in four" figure, be very sceptical – it's probably Dickensian-style doom-mongering disguised as social research, where the aim is to convince us, against the evidence of our own eyes and ears, that loads of the people we encounter everyday are basket cases in need of rescue.

I say "argues against", but he doesn't actually provide any arguments. He just links to the claims and says they're silly.

As Neuroskeptic readers know, I am myself skeptical of the idea that one in four people are mentally ill, but I'm skeptical of it because I've looked at the evidence and it doesn't support that figure. Actually, if you take the available evidence at face value, it says that the true figure for the lifetime prevalence is much higher than one in four. I don't think those figures are very useful however because of various methodological issues.

So in my view we just don't know how many people are mentally ill, largely because we don't have any clear definition of what "mentally ill" means. But that doesn't mean we can just assume that it can't possibly be one in four just because "our own eyes and ears" tell us that most people are not "basket cases".

Much mental illness goes undiagnosed and unnoticed, and I'd imagine also that Brendan O'Neill and the kind of people who read him don't tend to "encounter everyday" people from groups such as the unemployed, the elderly and so forth, in whom the rates are higher.

But even beyond that, it's a silly argument because of selection bias. If you as a healthy person encounter someone everyday, chances are they're not severely ill - mentally or physically - because if they were, they'd be less likely to be around in places for you to encounter. Unless you're a doctor or whatever, you live your life in the world of healthy people.

It's like saying that you don't believe children or the elderly exist, because in your life as a working age adult, you never meet any of them.

Time Well Spent

I woke up this morning feeling sick. My husband managed to pass along some kind of virus that seemed to only slow him down, but walloped me - as usual. My children always had that ability - a little runny nose and maybe a small cough for them, would grow horns for me. Since we are off to Hawaii tomorrow, I really needed to find a way to get better fast. Our flight is early and our house sitters would be coming by to get acclimated to the house and Lucy's schedule. (Yes, Lucy has babysitters - don't all Labs?)

So I found myself with time on my hands and needing something that would lift my spirits.

I found just the thing on Coast to Coast. For some of you that might be Coast to Coast listeners, the segment on Transformation and Life Purpose was one of the best segments I've listened to so far. I'm a member, so I can download any show and listen to it in my own time. Coast to Coast has plenty of negative and even some scary stories and guests on occasion, but the one on November 14th was truly delightful.

Jack Canfield, of the Chicken Soup for the Soul series, has co-written a new book with William Gladstone that has just been released. The Golden Motorcycle Gang has gone on my Christmas gift list. Jack Canfield is an incredibly good speaker. He is very down to earth and easy to understand. His message is one of hope and joy, and I found myself feeling so much better after listening to them talk about what they believe is the true meaning of 2012 and what is currently going on with current events. They talked about how to use specific skills to manifest those things that we want to see in our lives, especially our life purpose. We are here right now for a reason, and we chose this time for a reason. Every single person on this planet is important to what is happening - and I believe we are birthing a new evolution of mankind. I think that is what the Mayans are saying - it is the end of a cycle and the beginning of a new one. And we are driving it home.

People actually called the show and were crying, they were so touched by the dialog.

Just from listening to these guys speak for a couple of hours I feel that I am doing what I came here to do. I think I came here to write this blog, for one thing -  maybe to be someone that points people in directions they may not have considered, giving them the ability to make up their own minds. Maybe to do the research that they may not have time to do. To possibly write a book, maybe on shared-resources living. To be of service - in whatever small way that I can.

So what do you think? Am I on the right track?

Have you found your life purpose? (Hint - it is whatever brings you the most joy.)

ADDENDUM:  My brother called during the writing of this post to say that the business he decided to start, after quitting a good-paying job in this job market, is taking off like wild fire. He said for the first time in many, many, years he is having FUN!

Social Media

Many of you may have noticed that I no longer have a blog roll with all of your blogs on my sidebar. It is something that I miss - it is so easy to keep up when you update your blog with a new post, and I have fallen behind by not having this convenience. However, this was an intentional move to protect my readers. When writers Trish and Rob MacGregor were hacked several months back, a few of their blogging friends were also hacked. It was nasty - they hacked their email accounts, ruined a computer, literally made their lives miserable.

I closed my blog - totally eliminated it, and started a new one which I kept personal until it was clear I was not a target. But I began to worry about my readers. If for some reason I attracted a bad element - I didn't want my readers to also be pulled into the mess. Lucky for me, that has not happened. But for many, social media is becoming intrusive and worrisome.

This article about a mother who found her children were being used in an unauthorized manner makes the case for being very careful about what information you give to social media sites, and especially if you link them. In this case a mother found her children being used on one site, without them ever signing on to that site, just from them being a friend on her Facebook, and leaving a message on her Wall.

This is scary. The idea that information can be swiped and used throughout the internet is of major concern.

So be aware that when you sign on to your blog, twitter, Facebook, etc., that everything you write is public domain - even your children.

Modern War-fMRI : Graphics Cards for Science

Videogames and neuroscience have a rocky relationship.

On the one hand you have Susan Greenfield and her games-hurt-the-brain theory. But she's not representative of neuroscientists as a whole: games have also helped neuroscience, for example, in this study of the neural correlates of "flow" experiences.

Now neuroscientists have another reason to be thankful for games, according to a new paper. It turns out that modern 3D graphics cards - which mostly exist in order to render videogame visuals - can be used to do fMRI data analysis.

According to Sweden's Eklund et al, a graphics card can perform intensive fMRI analysis hundreds of times faster than a regular processor of the equivalent speed, because graphics processors make use of parallel computing optimized for 3D images and that's ultimately what all brain scans are.

They developed a way to run non-parametric statistical analyses of brain imaging data. Proponents say that non-parametric stats have many advantages over conventional parametric ones - and they're certainly becoming increasingly popular. But they involve doing far more calculations. Thousands of times more, in some cases.

It turns out though that armed with 2.5 GHz CPU and three NVidia GTX 480s, and making use of NVidia's graphics programming language, they were able to cut the time to analyse one person's brain with 100,000 permutations, from 24 hrs to just 9 minutes. The whole setup cost $4000, so it's not cheap, but they say it's "a fraction of the price for a PC cluster with equivalent computational performance" i.e. one relying on lots of general purpose processors, rather than graphics cards. Even on GTX480 did the job very well.

Best of all, this gives neuroscientists an excuse to spend their grant money on awesome gaming rigs. Why do I want the latest GForce on my work computer? To do non-parametric data analysis, obviously. Sure, it would also allow me to run Modern Warfare 3 at the highest settings... but that's not why I want it.

Eklund A, Andersson M, Knutsson H (2011). Fast random permutation tests enable objective evaluation of methods for single-subject FMRI analysis. International journal of biomedical imaging, 2011 PMID: 22046176

Occupy With Aloha

Photo courtesy of Yes Lab

For many of us who are becoming uneasy with some of the problems associated with Occupy Wall Street, the rapes, the degradation of community parks, the shootings, the fear that it will become a haven for some of society's most violent, what we are most uneasy about is the possibility that the message will be lost. The message - that 99% of our population has been forgotten, left out of the American Dream, while the other .09% has amassed the majority of the wealth of our great nation. That Wall Street used banks like casinos and we are left with the carnage of their greed, an economy on the brink of destruction. What is left for the rest of us is massive debt and jobs that are no longer in our country, but in foreign nations that do not have laws protecting the rights of their workers, thus enabling them to sell us their cheap products, while we borrow from those same countries to pay our teachers and fireman.

Our politicians very often come out of Washington much more wealthy than they were when they took their vows to honor the will of the American people. They often do this with inside information that the rest of the country does not have access to - just as Nancy Pelosi and her husband did with a credit card company. Soft corruption, honest graft. Insider trading in the stock market. Writing the rules so that they do not apply to themselves! Taking information learned in committee meetings and using it to make stock market trades. The rest of us go to prison for doing many of the things our politicians routinely do to line their pockets.

So when I found this post on Synchrosecrets, I asked Trish and Rob if I could repost it in its entirety. Here is one man's very brave stand for the other 99%.

WE ARE THE MANY, NOT THE FEW

Here’s an interesting twist in the Occupy movement.

Hawaiian recording artist Makana was supposed to play a luau Saturday night – November 12 – at Waikiki Beach for leaders at an annual summit that is putting together plans for a Pacific free-trade pact.  The Obamas and leaders of 21 economies from the Asia Pacific were present. Among the attendees were Chinese President Hu Jintao and Russian President Dmitry Medvedev. Security was apparently tight.

So there they are, these leaders, doing whatever leaders do at a private shindig on Waikiki Beach, and the young man who is supposed to play for the Hawaiian feast opens his jacket to reveal a t-shirt that reads, Occupy for Aloha. The five-minute song in the video is what he sang repeatedly for forty minutes. Here’s the refrain I love:

“We’ll occupy the streets, we’ll occupy the courts, we’ll occupy the offices of you, till you do the bidding of the many, not the few.”

Ripping Off The Masks

I've mentioned before in this space of my belief that we are part of something sweeping the world. One of the outcomes of this new energy is that masks that shroud and camouflage are being ripped away at lightening speed. In the last week alone I've read of a high ranking CDC scientist being arrested for bestiality and child sexual abuse, the horrific Penn State scandal with a coach that put football above the protection of children, and of a documentary made in the mid 1990's that was squashed before it could be viewed on Discovery Channel. All known copies were purchased and destroyed by an unknown entity. The film exposed the organized abuse of children through Boys Town -  and was another case of people in the highest echelons of business and government hiding evil proclivities and abusing children that are most vulnerable.

Each day we read about wannabe-be politicians who have sexually harassed women and lie to cover it up, corporate executives that have the highest of incomes cheating their companies and their employees, Ponzi schemes, greedy bankers using the public trust like a casino, priests that abuse young boys being protected by those in power above them. The list goes on and on.

What is happening here?

It's time for humanity to clean up its act. And those that are practicing evil had better watch out, because they are no longer operating in the same system that has protected them for so long.

So each time you hear of a mask being ripped from the face of someone who deserves to be exposed - don't despair in humanity - let out a cheer instead. It's bringing us that much closer to a world that no longer tolerates these activities, or the people that perpetrate them.

Autism: What A Big Prefrontal Cortex You Have

A new paper has caused a lot of excitement: it reports large increases in the number of neurons in children with autism. It comes to you from veteran autism researcher Eric Courchesne.

Courchesne et al counted the number of cells in the prefrontal cortex of 7 boys with autism and 6 non-autistic control boys, aged 2-16 years old. The analysis was performed by a neuropathologist who was blind to the theory behind the study and to which brains were from which group. That's good.

They found that the total brain weight of the brain was increased in autistic boys, by about 17% on average. But the number of neurons in the prefrontal cortex was increased by an even higher margin - about 60%. The difference was specific to neurons - glial cell counts were normal. Of the 7 autistic boys, 4 also had intellectual disability - an IQ less than 70. However, the 3 without showed broadly similar results.

As well as having more prefrontal neurons, there were also some other issues in some but not all of the autism brains. Two had prefrontal cortical abnormalities - dysplasia in one case and abnormal cell orientation in another. And no fewer than 4 had flocculonodular lobe dysplasia in the cerebellum.

None of the nonautistic brains had any abnormalities reported but they don't seem to have looked very closely in the controls because that was based on "coroner's report only", rather than a detailed neuropathological exam...

It's a nice piece of work, but very small. These postmortem neuropathology studies always are because postmortem brain samples are in short supply, especially for disorders like autism.

In fact, it's so small, that doing statistics on these data is not really meaningful. The authors do some stats and get some impressive p values but we should take those with a pinch of salt and just look at the individual data (see the scatterplots above).

Now, prefrontal cortical neurons are generated while you're still in the womb. New ones can't be created after you're born - numbers can only decrease. So the increased neuron count in autism must have a very early origin, either genetic or caused by pre-natal environmental factors. Unless the timeline for cell genesis is totally different in autism.

Still, it casts doubt on the idea that, in the brain, bigger is always "better". Assuming that we consider autism to be "bad" - which I'm not saying is necessarily right, but it's fair to say most people do assume that - then the common practice of equating volume increases with all kinds of good things seems rather silly.

Courchesne E, Mouton PR, Calhoun ME, Semendeferi K, Ahrens-Barbeau C, Hallet MJ, Barnes CC, & Pierce K (2011). Neuron number and size in prefrontal cortex of children with autism. JAMA : the journal of the American Medical Association, 306 (18), 2001-10 PMID: 22068992

Planting the Seeds

Dr. Kashonia has done a great post on planting the seeds for our future at this sacred time. She says the energy or force is with us over the next few days. In another post she talks about this special date, and what is believed to be happening to our DNA, among other things.

So start thinking about your future.  Now is the time to plant the seeds that will grow. 

I am continuing to work on my shared-resources communities - in fact I hope to visit one or two in the next year. At least that's my goal. (Thanks for your comment yesterday, Chris!)

Here is one idea that I just loved - a whole apartment building in Berlin of like-minded people. The price for these ten apartments came out to just $146,000 per space. Granted, some of the apartments may be bigger than others, so those would be more expensive, but still - much less than your average condo would cost almost anywhere. The designer said he cannot imagine living any other way. Being able to ring a doorbell, have communal parties, feeling completely safe, made his vision a success.

As mentioned in my last post, my family is exploring business ideas. One daughter is designing the teacher she wants to be, while finishing up graduate work. She will be teaching junior high school-level students, and thinks of them as her little "peaches." I love that, since adolescents are near and dear to my heart as well. Our educational system needs an overhaul - I applaud her desire to be the best she can be.

We are attending a wedding today for some very dear friends who will get married at 11:00 a.m. on 11-11-11 - all without ever paying attention to the date or time! I guess they don't believe in the cosmic prompt.

But for those of us who do believe in the unseen - this date is powerful, so whatever dreams you have, bring them out, dust them off, and lets see what happens. If nothing else, do something today that you enjoy, that makes you happy, and above all - be positive. We live a shared dream, a hologame of sorts, and for everyone that is thinking good thoughts - the rest benefit. Magnify the energy! We can use all the good you can muster.

Another Antidepressant Bites The Dust

Yet another up-and-coming antidepressant has flopped.

A paper just out reveals that the snappily-named GSK372475 doesn't work and has lots of side effects. It's a report of two clinicals trials in which Glaxo's contender was pitched against placebo and against older antidepressants in the treatment of depression.

GSK372475 failed to improve depression any better than placebo, even though the trials were large (393 and 504 patients respectively) and twice as long as most antidepressant trials (10 weeks whereas 4 or 6 is more usual)which ought to have given it plenty of room to shine.

The comparison drugs, the widely used venlafaxine and paroxetine, did work. A bit.

One of the trials even used the Bech "Melancholia Subscale" as an outcome measure, which Neuroskeptic readers may remember as I've praised it before. Venlafaxine worked on that, GSK's new pill didn't. If anything, the new drug was worse than placebo, in that patients improved slower.

In terms of side effects it caused dry mouth, insomnia, and nausea serious enough to make many people quit the study early. But even worse, it raised heart rate by almost 10 beats per minute on average, which is really never a good sign.

So, overall, it was an utter flop. In one sense this is not surprising. New "antidepressants" that don't work in trials have been all too common recently. Just last week we learned about the failure of "Serdaxin" in a Phase II trial. Actually Serdaxin isn't a new drug but an old antibiotic called clavulanic acid that a company was trying to rebrand as a mood lifter.

However the failure of GSK372475 is a bit of a mystery. The drug is a potent triple reuptake inhibitor (TRI) which acts on the neurotransmitters serotonin, noradrenaline and dopamine. By contrast, venlafaxine is a double reuptake inhibitor which doesn't hit dopamine, and paroxetine only targets serotonin. I've written about other TRIs before.

Now it seems surprising that venlafaxine worked, but a TRI didn't, in the same trial. That would imply that blocking the reuptake of dopamine makes you more depressed, enough to cancel out the other actions which are shared with venlafaxine. Which is not what I'd have predicted.

There are other differences between the drugs though. Venlafaxine has a very short half-life - it's broken down in the body in a matter of hours. But GSK372475 has a halflife of 8-10 days. Could this be the problem?

Learned S, Graff O, Roychowdhury S, Moate R, Krishnan KR, Archer G, Modell JG, Alexander R, Zamuner S, Evoniuk G, & Ratti E (2011). Efficacy, safety, and tolerability of a triple reuptake inhibitor GSK372475 in the treatment of patients with major depressive disorder: two randomized, placebo- and active-controlled clinical trials. Journal of psychopharmacology (Oxford, England) PMID: 22048884

Entrepreneurship

Our family is currently exploring the idea of starting a couple of different businesses. Several ideas are being floated, and nothing is firm yet, but the energy is flowing and ideas are popping.

We come into this with a variety of skills and experience in a number of fields - finance, research, investor relations, accounting, management, computer modeling, experience with start-ups, resource development, alternative energy, human development, psychology, human relations, marketing, teaching, cooking, writing.

Surely we can create a business opportunity, don't you think?

If fact, I would bet that you have family and/or friends that come with a variety of skill sets that create something completely different when you put them all together. The whole is greater than the sum of its parts.

I would also bet that same set of family/friends have some great ideas - just simmering on the back burner.

New ideas, new businesses, fresh starts. I think we're going to have create our own opportunities in the future. Maybe we can do it the way it should be done - with mindfullness, gratitude, and environmental awareness. 

Chemtrails

I have been following a rather disturbing story for awhile now. Chemical trails are not what we think they are - they are not just contrails from airplanes flying at high altitudes. Needless to say, this is deeply disturbing information - especially because it is being done in secret. CMN has been on this story for some time, and as the mother of an asthmatic daughter, I find this information chilling.

The island of Maui is trying to detour all airplanes from flying over the island because the organic produce being grown on the island is no longer organic.

The following video is short - only 10 minutes - and is one that everyone should watch. It's time to wake up to what is going on around us, and more importantly, to us.