A Grand Unified Theory of Autism?

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)...

Markram K, & Markram H (2010). The intense world theory - a unifying theory of the neurobiology of autism. Frontiers in human neuroscience, 4 PMID: 21191475

A Grand Unified Theory of Autism?

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)...

Markram K, & Markram H (2010). The intense world theory - a unifying theory of the neurobiology of autism. Frontiers in human neuroscience, 4 PMID: 21191475

Left Wing vs. Right Wing Brains

So apparently: Left wing or right wing? It's written in the brain

People with liberal views tended to have increased grey matter in the anterior cingulate cortex, a region of the brain linked to decision-making, in particular when conflicting information is being presented...

Conservatives, meanwhile, had increased grey matter in the amygdala, an area of the brain associated with processing emotion.

This was based on a study of 90 young adults using MRI to measure brain structure. Sadly that press release is all we know about the study at the moment, because it hasn't been published yet. The BBC also have no fewer than three radio shows about it here, here and here.

Politics blog Heresy Corner discusses it...

Subjects who professed liberal or left-wing opinions tended to have a larger anterior cingulate cortex, an area of the brain which, we were told, helps process complex and conflicting information. (Perhaps they need this extra grey matter to be able to cope with the internal contradictions of left-wing philosophy.)

This kind of story tends to attract chuckle-some comments.

In truth, without seeing the full scientific paper, we can't know whether the differences they found were really statistically solid, or whether they were voodoo or fishy. The authors, Geraint Rees and Ryota Kanai, have both published a lot of excellent neuroscience in the past, but that's no guarantee.

In fact, however, I suspect that the brain is just the wrong place to look if you're interested in politics, because most political views don't originate in the individual brain, they originate in the wider culture and are absorbed and regurgitated without much thought. This is a real shame, because all of us, left or right, have a brain, and it's really quite nifty:

But when it comes to politics we generally don't use it. The brain is a powerful organ designed to help you deal with reality in all its complexity. For a lot of people, politics doesn't take place there, it happens in fairytale kingdoms populated by evil monsters, foolish jesters, and brave knights.

Given that the characters in this story are mindless stereotypes, there's no need for empathy. Because the plot comes fully-formed from TV or a newspaper, there's no need for original ideas. Because everything is either obviously right or obviously wrong, there's not much reasoning required. And so on. Which is why this happens amongst other things.

I don't think individual personality is very important in determining which political narratives and values you adopt: your family background, job, and position in society is much more important.

Where individual differences matter, I think, is in deciding how "conservative" or "radical" you are within whatever party you find yourself. Not in the sense of left or right, but in terms of how keen you are on grand ideas and big changes, as opposed to cautious, boring pragmatism.

In this sense, there are conservative liberals (i.e. Obama) and radical conservatives (i.e. Palin), and that's the kind of thing I'd be looking for if I were trying to find political differences in the brain.

Links: If right wingers have bigger amygdalae, does that mean patient SM, the woman with no amygdalae at all, must be a communist? Then again, Neuroskeptic readers may remember that the brain itself is a communist...

Left Wing vs. Right Wing Brains

So apparently: Left wing or right wing? It's written in the brain

People with liberal views tended to have increased grey matter in the anterior cingulate cortex, a region of the brain linked to decision-making, in particular when conflicting information is being presented...

Conservatives, meanwhile, had increased grey matter in the amygdala, an area of the brain associated with processing emotion.

This was based on a study of 90 young adults using MRI to measure brain structure. Sadly that press release is all we know about the study at the moment, because it hasn't been published yet. The BBC also have no fewer than three radio shows about it here, here and here.

Politics blog Heresy Corner discusses it...

Subjects who professed liberal or left-wing opinions tended to have a larger anterior cingulate cortex, an area of the brain which, we were told, helps process complex and conflicting information. (Perhaps they need this extra grey matter to be able to cope with the internal contradictions of left-wing philosophy.)

This kind of story tends to attract chuckle-some comments.

In truth, without seeing the full scientific paper, we can't know whether the differences they found were really statistically solid, or whether they were voodoo or fishy. The authors, Geraint Rees and Ryota Kanai, have both published a lot of excellent neuroscience in the past, but that's no guarantee.

In fact, however, I suspect that the brain is just the wrong place to look if you're interested in politics, because most political views don't originate in the individual brain, they originate in the wider culture and are absorbed and regurgitated without much thought. This is a real shame, because all of us, left or right, have a brain, and it's really quite nifty:

But when it comes to politics we generally don't use it. The brain is a powerful organ designed to help you deal with reality in all its complexity. For a lot of people, politics doesn't take place there, it happens in fairytale kingdoms populated by evil monsters, foolish jesters, and brave knights.

Given that the characters in this story are mindless stereotypes, there's no need for empathy. Because the plot comes fully-formed from TV or a newspaper, there's no need for original ideas. Because everything is either obviously right or obviously wrong, there's not much reasoning required. And so on. Which is why this happens amongst other things.

I don't think individual personality is very important in determining which political narratives and values you adopt: your family background, job, and position in society is much more important.

Where individual differences matter, I think, is in deciding how "conservative" or "radical" you are within whatever party you find yourself. Not in the sense of left or right, but in terms of how keen you are on grand ideas and big changes, as opposed to cautious, boring pragmatism.

In this sense, there are conservative liberals (i.e. Obama) and radical conservatives (i.e. Palin), and that's the kind of thing I'd be looking for if I were trying to find political differences in the brain.

Links: If right wingers have bigger amygdalae, does that mean patient SM, the woman with no amygdalae at all, must be a communist? Then again, Neuroskeptic readers may remember that the brain itself is a communist...

The Ethics of Getting as High as a Kite

Are drugs good or bad?

I mean, in the ethical sense. Medically, all drugs have potential harms variously associated with use, long-term use, overdose, etc. Politically, by buying illegal drugs, you're probably ultimately funding criminals and terrorists (although you might well blame prohibition, not drugs, for that). But setting that aside, assuming no-one gets harmed as a result: is it morally wrong to take recreational drugs per se?

It's an important question, because your opinion about this will influence your opinions about less abstract, more immediate issues: whether cannabis ought to be sold in coffee shops, how many years you should spend in jail for dealing coke.

However, no-one really asks this question, directly. The medical and the political aspects of drugs are endlessly debated, but after listening to these arguments for a while, you'll realize that while people on both sides talk about public health risks and harm reduction, most of the time they're really just disagreeing about the abstract question of whether taking drugs for fun is acceptable.

Here's the two major schools of thought as I see them. There are those who see no problem with recreational drug use, assuming no-one gets hurts. If it feels good, it is good. If it makes people happy, what's not to like? If people want to enjoy themselves in that particular way, it's no-one else's business. Call this the 'hedonist' view.

On the other hand, there are those who see drug use as a shameful escape from reality. There's more to life than "having fun", life is serious. You ought to be out there doing something, not just sitting around with a silly grin on your face. That's cheating, getting enjoyment for nothing. Call this the 'puritan' school.

People differ on which one they favour, but most of us identify with both to some extent. Few people are puritan enough to forgo all of life's pleasures, not even a quiet drink or a hot bath. Few hedonists would be happy if their own kids announced that they had no ambition to succeed in any kind of career, they'd just live off their inheritance and buy heroin.

As a whole, society has a mixed view. We have a puritanical objection to people who just take drugs and do nothing else with their lives; "junkies", "crackheads", "alkies". But we have no problem with drug use by people who clearly have engaged with the world, and succeeded.

Musicians, actors, and other stars take industrial quantities of drugs. Everyone knows it. It's not even an open secret in most cases, it's just open. Even gossip columnists don't notice unless someone gets so far gone that they do something funny. We don't care, because, whether or not we actually like their work, they're not just drug users, they're also doing their jobs.

The Ethics of Getting as High as a Kite

Are drugs good or bad?

I mean, in the ethical sense. Medically, all drugs have potential harms variously associated with use, long-term use, overdose, etc. Politically, by buying illegal drugs, you're probably ultimately funding criminals and terrorists (although you might well blame prohibition, not drugs, for that). But setting that aside, assuming no-one gets harmed as a result: is it morally wrong to take recreational drugs per se?

It's an important question, because your opinion about this will influence your opinions about less abstract, more immediate issues: whether cannabis ought to be sold in coffee shops, how many years you should spend in jail for dealing coke.

However, no-one really asks this question, directly. The medical and the political aspects of drugs are endlessly debated, but after listening to these arguments for a while, you'll realize that while people on both sides talk about public health risks and harm reduction, most of the time they're really just disagreeing about the abstract question of whether taking drugs for fun is acceptable.

Here's the two major schools of thought as I see them. There are those who see no problem with recreational drug use, assuming no-one gets hurts. If it feels good, it is good. If it makes people happy, what's not to like? If people want to enjoy themselves in that particular way, it's no-one else's business. Call this the 'hedonist' view.

On the other hand, there are those who see drug use as a shameful escape from reality. There's more to life than "having fun", life is serious. You ought to be out there doing something, not just sitting around with a silly grin on your face. That's cheating, getting enjoyment for nothing. Call this the 'puritan' school.

People differ on which one they favour, but most of us identify with both to some extent. Few people are puritan enough to forgo all of life's pleasures, not even a quiet drink or a hot bath. Few hedonists would be happy if their own kids announced that they had no ambition to succeed in any kind of career, they'd just live off their inheritance and buy heroin.

As a whole, society has a mixed view. We have a puritanical objection to people who just take drugs and do nothing else with their lives; "junkies", "crackheads", "alkies". But we have no problem with drug use by people who clearly have engaged with the world, and succeeded.

Musicians, actors, and other stars take industrial quantities of drugs. Everyone knows it. It's not even an open secret in most cases, it's just open. Even gossip columnists don't notice unless someone gets so far gone that they do something funny. We don't care, because, whether or not we actually like their work, they're not just drug users, they're also doing their jobs.

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