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Kon
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05 Jan 2011, 1:36 pm

A physicist famously wanted to find the grand unifying equation behind the laws of nature, in a form that you could put on a t-shirt.

Neuroscientists Kamilla and Henry Markram have proposed a grand unifying theory of autism, and the key to it is in this picture. I wouldn't want to be seen wearing it quite yet, but if the theory pans out, I'm sure we could come up with a more torso-friendly diagram.

So what does this mean? The Markrams call their idea the Intense World Theory. Essentially, they propose that all of the diverse symptoms of autism are direct or indirect consequences of the autistic brain's being hyper-responsive to stimuli. (They published an earlier version of this theory in 2007).

Not the brain as a whole, and not each individual cell, either. Rather, they say that the abnormality lies in local microcircuits. The best known of these are the cortical columns and minicolumns. Neurons in any given microcircuit are connected both with their neighbors, and with more distant cells. A bit like a large company with offices in different cities: people within each office talk to each other, but they also phone and email the other branches.

The theory goes that the autistic brain has too many connections within any given microcircuit. So, when the circuit is activated, it reactivates itself too strongly, and shows a stronger, and longer, excitation. A bit like if the offices were open-plan, so everyone can overhear everyone else, and it all gets very noisy.

So what's the evidence for this? There's circumstantial support. It "makes sense", if you're willing to accept an analogy between hyperactive local neural circuits and hyper-intense psychological phenomena.

We know that a given cortical minicolumn responds to a particular type of stimulus, or aspect of a stimulus; there are minicolumns for horizontal lines, for lines at 10 degrees to the horizontal, and so on. People with autism are often fixated on little details. It's a leap, but not an impossible one, to see these as related.

But the only really direct biological evidence is from rats. The story starts with valproate (VPA), an effective anticonvulsant also widely used in bipolar disorder. VPA has to be used with extreme caution in women because of the risk of birth defects.

Children whose mothers take VPA (and to various degrees other similar drugs) during pregnancy often suffer various physical and behavioural problems, the fetal anticonvulsant syndrome. Sadly, this happened quite a lot in the past, before the risks were appreciated. The key point is that autistic symptoms extremely common in children exposed to high-dose VPA.

Markram (and other people) have studied rats exposed to valproate in the womb. They found that, well, they're weird. Proponents would say that they behave a lot like how an "autistic" rat would: they are less sociable, prone to repetitive behaviours, highly anxious, etc.

Can a rat "have autism"? That's one to ponder. On the one hand, rats are surprisingly smart, sociable animals. For every human brain region, there's a rat equivalent in roughly the same place, which does roughly the same thing. They have cortical columns and minicolumns like ours (we just have more of them). They even "laugh" when you tickle them. On the other hand... they're rats. They run around gutters eating trash.

The t-shirt image at the top of this post is based on Markram and colleagues work on the cortical network properties of VPA-exposed rats (e.g. this and several other studies). These studies revealed hyper-connectivity within local microcircuits, and have also shown that circuits from VPA-exposed rats "learn" faster: they form new synaptic connections via the process of LTP at an accelerated rate, likely due to over-expression of NMDA glutamate receptors.

They admit that it's a big leap from that to human autism. But it's not an impossible leap. As they say:

This provided the potential cellular and circuit explanation for how an autistic brain could be easily trapped in a painfully intense world, potentially explaining a broad range of common autistic symptoms such as sensory sensitivity, withdrawal, repetitive behavior, idiosyncrasies, and even exceptional talents.

The major attraction of the theory is that it is a unified one: it seems to explain everything about autism, although maybe it's just vague enough to be stretched to cover anything. For example, Markram attributes the social awkwardness of autistic people to an overactive amygdala, which makes them extremely anxious in social situations, especially when meeting people's gaze; this, he says, means that they quickly learn to avoid other people in an attempt to cope with this Intense World.

Henry Markram is best known as the leader of the Blue Brain Project, which aims to simulate a brain using supercomputers. So he's no stranger to big ideas. Whether this idea is as solid as it is big remains to be seen, but I think he's to be applauded for at least having a crack at a unified account of autism, something which, as far as I know, no-one else has had the guts to try yet (Edit: But see the comments for a debate on that question)...


http://neuroskeptic.blogspot.com/2011/0 ... utism.html
http://www.ncbi.nlm.nih.gov/pmc/article ... -00224.pdf



Moog
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05 Jan 2011, 2:37 pm

Hmm, interesting. So they are suggesting that there is an envoronmental cause after all? It's certainly bold. Well, I'm watching this thread.


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rdos
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05 Jan 2011, 2:48 pm

This is no better than SBCs "extreme maleness theory". In fact, it is a lot worse because of the proposed links to VPA defects.

So lets debunk it for a while:
* Hyperactivity is not an universal in ASCs, although there is some kind of correlation
* Sensory acuteness is also not universal in ASCs. It is not even that common.
* This one is much worse: Hyperactivity is NOT related to sensory acuteness
* Stereotypical behaviors are NOT inherited. They are environmental
* Overload in social situations is NOT related to sensory acuteness, but to manual decoding of social behaviors.

I think I'll rest my case here until somebody could explain the above problems.



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05 Jan 2011, 2:59 pm

rdos, what's ASC? I've not seen this acronym before.


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rdos
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05 Jan 2011, 3:05 pm

ASC = Autism Spectrum Condition. It is a neutral term used instead of ASD that does not imply that autism must be a disorder.



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05 Jan 2011, 3:13 pm

rdos wrote:
ASC = Autism Spectrum Condition. It is a neutral term used instead of ASD that does not imply that autism must be a disorder.


Thanks. I prefer condition to disorder too.


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05 Jan 2011, 4:44 pm

Moog wrote:
rdos wrote:
ASC = Autism Spectrum Condition. It is a neutral term used instead of ASD that does not imply that autism must be a disorder.


Thanks. I prefer condition to disorder too.

Me too. :D


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05 Jan 2011, 5:12 pm

Sounds interesting. Maybe because I like the Grand Unified Theory in the title.
It's like the neurologists beat the physicists.
I'm going to look more into this.

A bit off topic:
Someone recommended I take Valporate for seizures. As an autistic sensitive to medications should I not take this?


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05 Jan 2011, 5:18 pm

I guess I have problems with the whole idea of a "Grand Unified Theory of Autism". This seems like conceptual overreach. RDOS points out a few problems with the theory itself. A bigger problem with such a "unified" theory is that there is no truly objective test for autism. How can you unify a theory around a phenomenon when there is no clear definition of what that phenomenon is? Until you can take a population and separate it cleanly into autistic and not autistic, or even objectify placement on a spectrum, you can't begin to have any real progress towards working out cause and affect. I'll bet I could go to 10 different mental health professionals and unless I pushed them towards examining autism, it wouldn't even come up. If the professionals in the field can't correctly identify something, how can researchers even know what questions to ask? This is what I think Simon Baron Cohen is reaching towards with his work, even if it is questionable on several fronts. He seems to be working pretty hard on an 'autism specification'. This Intense World theory is interesting, but it seems they are falling into the same pit as SBC and taking their ideas too far, too fast.


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05 Jan 2011, 5:35 pm

OK, I don't agree with the Valporate theory.
I do think there is both overactivity and under activity in parts of the autistic brain.
My theory is the Somatic nervous system has the over activity. That is the sensory centre and the area that controls movement.
Or maybe mine is just over active? I have many issues in this area.
I read in a journal that the frontal lobes are under active in HFA.
I still believe that there are many causes of autism. In my case I had trauma in the womb though my dad shows AS traits and my mum ADHD.


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05 Jan 2011, 5:43 pm

The physicist never got his T shirt. In fact his attempts at explaining got the Supercollider proect cancelled. Leon Lederman, in The God Particle.

Particle Physics is easy, few particles, lots of math to confirm them. The downfall is trying to include Time and Gravity, which have nothing to do with particles.

What he did find, before the plug was pulled, was particles that come in and out of being, regroup with others, in a cosmic dance where energy becomes matter, and matter becomes energy.

The "Wave/Particle Interface." would be a great name for a night club, for in a background of much vibration, much the same thing happens.

The brain is a bit more complex, lots of backup systems, storage, and the loss of half of it has had little effect on some. Data is not encoded in one spot, function is not dependent on some area, for human self removal through human actions, shows a holographic storage that continues memory, storage, function, after a proper hospital rest.

Left and Right Brain fails because people have lost each, and still function.

Extreme Male fails because the females of Wrong Planet include a lot of girly hotties.

Intense World Syndrom fails because it only explains interaction with the world.

Neutrons, Protrons, and Electrons have an orderly world, within that world view. they consider Quarks strange.

Every particle in the universe is just seeking a place where it feels stable.

We have skulls that show millions of years of brain development, and that speeded up over the last 50,000 years. The Neo Cortex is still new, a work in progress, and something like HDTV. Picture quality is much better, once you get it to work.

Older model TVs cannot read the new signals, and the new is mostly test prototypes, no two the same. It takes time, but when the new system works, history shows it replaces the old.

Fear is behind all Universal Models, a claim that old ways will not be recycled, a stable and unchanging universe with one unchanging set of rules. Homo Erectus held the same view of Homo Sapiens.

Autism, a differance in thought and perception, can take many forms, I think much has to do with incompatible conditions in which to develop.

Burning at the stake did solve the problem till 1700, then being chained to the wall deep in the celler. Then came state supported and private cellers, lots of experiments involving ice water and electroshock, then drugs, and various ideas why this was a good thing.

The Universal Model prevailed, we torture heratics to drive out the demons and save their souls. Almost everyone agreed this was for the best.

The long lamented decline in public order and morality turned loose people who had a differance in thought and perception, and technology boomed, destroying an order that had lasted for thousands of years.

The Markrams are close to the answer, they just failed to structure the question in all of it's forms, New things are not compatable with old things. There is truth there, I grew up with a radio with two knobs, now the one in the car has ten little black buttons, many modes, and while I did shut it off, the digital clock has been flashing 12:00 for years.

rdos has it right, all ASCs are a divergence from the norm of the past, and this divergence goes in all directions. While some may share some traits,
nothing is universal.

Even a mentally colsely matched pair, will get a very different reaction from the world if one is a skinny abused teen, and the other is a hundred kilos of might, and rich.

In nature, divergence is usual when things are just not working out like they used to. Destruction of habitat, over population, gadgets with lots of buttons, paper money backed by governments, declines of most things, like food supply, the land, air, and water, do lead to a stress that causes some to have other thoughts.

This stress effects future generations, like long wars produce babies who become warriors.

We are not the problem, we are the result of past problems.



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05 Jan 2011, 6:17 pm

For a more likely but not without problems idea:

http://autism.mit.edu/mottron

http://www.ncbi.nlm.nih.gov/pubmed/16453071


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Kon
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05 Jan 2011, 7:31 pm

I read the full pdf article and I really like the theory and find it very convincing with respect to describing many of my particular characteristics.



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05 Jan 2011, 7:48 pm

Kon wrote:
I read the full pdf article and I really like the theory and find it very convincing with respect to describing many of my particular characteristics.


Did your mum take valproate while you were gestating? I'd be surprised if mine did.


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05 Jan 2011, 8:08 pm

I think that wasn't supposed to be the only cause of autism. It was just an example of... something. (Migraine is stealing my brain.)


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