A very interesting article

[Guest guest]

A friend found this and sent it to me. I thought you all might like to

read it as well.

WELCOME TO MY WORLD

New Scientist, Sept 20 2008

IMAGINE a world where every sound jars like a jackhammer, every light is

a blinding strobe, clothes feel like sandpaper and even your own

mother's face appears as a jumble of frightening and disconnected

pieces. This, say neuroscientists Kamila and Henry Markram of the Swiss

Federal Institute of Technology in Lausanne, is how it feels to be autistic.

According to their " intense world " hypothesis, all of autism's baffling

and sometimes incongruous features - social problems, language

impairment and obsessive behaviour, sometimes allied to dazzling savant

abilities - can be explained by a single neurological defect: a

hyperactive brain that makes ordinary, everyday sensory experiences

utterly overwhelming.

If they're right - and the idea is generating a deal of interest among

autism experts - the husband-and-wife team could be on course to add a

significant new theory to autism research. " It is a very compelling

idea, " says neurobiologist Asaf Keller at the University of land

School of Medicine in Baltimore, who has arranged a symposium to discuss

it at November's Society for Neuroscience meeting in Washington DC.

Recognition of sensory disturbance in autism goes back as far as the

1940s, and today it is widely seen as a fundamental aspect of the

condition. " There is a lot of evidence for sensory hypersensitivity, "

says Simon Baron-Cohen, director of the Autism Research Centre at the

University of Cambridge. He notes that hypersensitivity can affect the

vision, hearing and touch of people with autistic spectrum disorders

(ASD, see " Autism basics "

<http://www.newscientist.com/article/mg19926741.700#bx267417B1>).

" If you talk to practitioners, invariably they will say, 'I've never

seen a child with autism who doesn't have sensory problems', " adds

Keller. " There's a strong correlation, maybe 100 per cent. "

The Markrams, however, are the first to put sensory overload at the

heart of the condition. " Our hypothesis is that autistic people

perceive, feel and remember too much, " says Kamila Markram. Faced with

this blooming, buzzing confusion, autistic infants withdraw, with

serious consequences for their social and linguistic development.

Repetitive behaviours such as rocking and head-banging, meanwhile, can

be seen as an attempt to bring order and predictability to a blaring

world (*Frontiers in Neuroscience*, vol 1, p 77

<http://dx.doi.org/10.3389/neuro.01.1.1.006.2007>).

Most theories of autism assume the affected person has a neurological

deficit of some kind - that some part of their brain isn't working

properly (see " Five leading theories of autism " )

<http://www.newscientist.com/article/mg19926741.700#bx267417B2>.

According to the Markrams' theory, though, the brain isn't

underperforming but overperforming.

System overload

Along with colleague Tania Rinaldi, they developed their hypothesis

largely from work on an animal model of autism, plus human brain

imaging, autopsy evidence and the subjective experiences of people with

ASD, including Henry Markram's son who is borderline autistic. " That's

the curse of having parents who are neuroscientists, they are constantly

analysing you, " says Kamila Markram. She has observed the boy's intense

fears and anxieties and his struggles with oversensitivity.

For the animal work they used an autism model called the VPA rat. This

model is based on dozens of case studies of children whose mothers took

the anticonvulsant and mood-stabilising drug valproic acid (VPA) while

pregnant. A frighteningly high proportion of these children ended up

with some form of autism - around 10 per cent, compared with some 0.08

per cent of the general population.

In the mid-1990s, researchers working on the adverse effects of VPA

tried exposing rat fetuses to the drug and found that giving it on the

12th day of gestation - equivalent to the early part of the first

trimester in humans - caused major damage to the rats' developing

brainstem. This has far-reaching effects on later brain development and

results in socially withdrawn behaviour that looks eerily similar to

humans with autism. The VPA rat is now an established animal model of

autism.

When the Markrams examined the brains of VPA rats in minute detail, they

found that they didn't just share behavioural traits with autistic

humans. Their neuroanatomical changes were similar too.

One of the most replicated findings in autism neurology is abnormal

brain growth. At birth the brains of autistic children are small or

normal sized, but grow unusually quickly. By age 2 to 3 their brain

volume is roughly 10 per cent larger than average. Human autopsy

findings by Casanova of the University of Louisville in Kentucky

suggest that part of this extra volume consists of structures called

minicolumns in the brain's outer layer, the cerebral cortex.

You can think of minicolumns as the brain's microprocessors: clusters of

around 80 to 120 neurons that crunch basic neural information, including

perception, memory and so on, before it is somehow integrated into a

whole. They are the smallest independent processing units in the cortex.

When the Markrams looked at minicolumns in VPA rats they saw some

striking changes similar to the human autopsies. First and foremost the

minicolumns were unusually abundant. They were also extraordinarily well

connected. " Using a technique for recording directly from neurons, we

found consistently, over many experiments, that these circuits are

hyperconnected, " says Kamila Markram. Each minicolumn neuron in a VPA

rat has up to 50 per cent more connections than normal and this causes

them to be hyper-reactive, firing more readily when stimulated by an

external electrical current. The circuits are also " hyperplastic " ,

meaning they form connections with other neurons more readily than normal.

Taken together, hyper-reactivity and hyperplasticity mean that

minicolumns in VPA rats (and presumably in autistic humans too) have a

higher than normal capacity for processing information. And this, say

the Markrams, is autism's fundamental problem.

Take sensory disturbance, for example. Excessive information processing

in the microcircuits that handle incoming data from the senses leads to

exaggerated perception, producing extremely intense images, sounds,

smells and touch, the Markrams claim. Hyperactive microcircuits,

meanwhile, could prove difficult to integrate into a whole, so

perception would be highly fragmented. This sensory overload causes

autistic kids to withdraw from the world, or pay excessive attention to

small fragments of it. " It's what anyone would do if they were embedded

in a welter or cacophony of unpredictable events, " says autism

researcher Belmonte of Cornell University, Ithaca, New York.

The hypothesis also provides an explanation for the three core deficits

of ASD. Social problems, for example, are a direct consequence of

children withdrawing from the world during critical developmental

windows. Because the developing human brain requires repeated exposure

to relevant stimuli at the right time to develop properly, early

avoidance of social stimuli can have a devastating effect on a child's

social development. " They don't learn because they don't interact, " says

Kamila Markram.

Similarly, children whose exposure to language during infancy is

inadequate will have impaired language skills all their lives. When

almost every sensation is overwhelming it's hard to socialise at all,

let alone speak.

Hyperplasticity, meanwhile, could account for repetitive behaviour and

the compulsive desire for routine in people with ASD. Plasticity

underlies learning and memory, so hyperplastic brains could be primed

for what the Markrams call " hypermemory " . " They build very strong

memories, " says Kamila Markram. " So strong that you establish a routine

that you can't undo: you are stuck on a track. "

At the same time, however, by locking them into specific narrow

interests and compelling them to practise compulsively, hypermemory may

be what drives some autistic people to develop savant skills. This

appears to be how musical, artistic and mathematical savants develop

their talents.

Unfortunately, if their focus is too narrow, savant-like skills can

appear to be the exact opposite. " If your focus of attention becomes too

local then you may become an expert on such a tiny system - the wheel of

your toy car, say - that you end up with very little demonstrable

knowledge about other, wider systems, " says Baron-Cohen.

Wired for fear

Another crucial element of the new hypothesis is that VPA rats also have

hyperconnectivity and hyperplasticity in the amygdala, the almond-shaped

brain structure where memories of fear are made and stored, which looms

large in many theories of autism. VPA rats learn to avoid frightening

situations more quickly than other rats, readily fear non-threatening

stimuli, and are quick to generalise fear from one situation to another.

They also have a much harder time learning that a once-scary situation

is now safe (*Neuropsychopharmacology*, vol 33, p. 901

<http://dx.doi.org/10.1038/sj.npp.1301453>).

Assuming humans also have these changes in their amygdala, this could

further explain some of the symptoms of autism. As a result of an

overactive amygdala, says Kamila Markram, autistic people find the world

" not only intense, but also aversive " . Ordinary situations can be

terrifying and fear is easy to learn and hard to forget. This is another

reason why autistic people prefer predictable, repetitive routines and

can overreact, sometimes explosively, to change.

So far the intense world hypothesis is playing well with autism experts.

" I really think it is spot on, " says Belmonte. " For some years the

autism literature has needed a greater focus on the idea of autistic

behaviour as a normal response to an abnormal perceptual and cognitive

world. " Baron-Cohen too sees many positives. While he disagrees with

some aspects of the idea, overall, he says: " The attraction of the

research is to find basic differences between the autistic and typical

brain, out of which higher cognitive differences such as in systemising

may develop. In this view, the higher cognitive differences are

secondary to these more basic sensory differences. This is a view I have

a lot of sympathy with. "

It also rings true with autistic people. " When I was younger, the school

bell was like a dentist's drill hitting a nerve, " says Temple Grandin,

an animal scientist at Colorado State University in Fort well

known for being autistic. " I think it's difficult for people to imagine

a reality where sounds hurt your ears and a fluorescent light is like a

discotheque, " she says. The Markrams have also received a positive

response from families affected by ASD. " It gives them comfort, " Kamila

Markram says, " there are actually reasons why these children aren't

responding well. "

Some experts, however, are not convinced. The strongest critique comes

from those who think the hypothesis extrapolates too much from the VPA

rat. " [The Markrams are] extremely good on the neurophysiology... but we

don't yet know how to translate what the neurons are doing to what's

happening psychologically, " says neuropsychologist Frith at

University College London. " I think they made a leap too far. "

Keller, however, defends the use of animal models, noting that VPA

causes the same anatomical and behavioural abnormalities in humans,

monkeys and mice. " I see it not as a model, but as a recapitulation of

the disease in other species, " he says.

These arguments aside, the intense world theory also has implications

for the debate over the ultimate causes of autism. Although autism is

highly heritable, genes alone are not enough to explain it; in pairs of

identical twins where one twin has autism, the other is affected only 60

per cent of the time at most.

The VPA rat's striking similarities to autism suggest that the condition

might arise early in pregnancy when an as-yet unknown environmental

insult combines with genetic vulnerability to damage the brainstem at a

vital time. " What this study emphasises is not genetics but

environment, " says Casanova. " It also emphasises the idea of a window of

vulnerability. The timing of the insult is of great importance. "

This could also explain the wide range of the autistic spectrum, from

severe impairment requiring 24-hour care to the near-normality of

high-functioning Asperger's. The later in the window exposure occurs,

the less wide-ranging the attack on the fetal brainstem would be,

reducing the subsequent damage as more regions would already have had

time to develop unharmed.

Testing times

So how can the intense world idea be tested further? One way is to look

for a correlation between sensory problems and the severity of ASD. If

people with the worst oversensitivity - as measured by reactions to

light, sound and touch - have the most incapacitating autism, that would

offer support. And if intervening early in sensory problems mitigated

the symptoms of autism this would also be evidence in favour.

Keller is collaborating on just such a study with researchers at s

Hopkins University in Baltimore, land, who have pioneered early

detection in children as young as 6 months. Together they are looking at

autistic children at the earliest possible stage to see whether reducing

their sensory overload can help. Strategies include noise-reducing

headphones and other ways of producing calmer, less stimulating

environments.

These same measures already work for children who have endured severe

early trauma and neglect, such as being raised in an understaffed or

abusive orphanage. These children often have overactive amygdalas,

heightened fear memories, are withdrawn and exhibit repetitive

behaviours indistinguishable from autism.

The results of early intervention to help autistic children will be

watched with interest, not least because one of the most striking

features of the intense world hypothesis is that it casts almost

everybody on the autistic spectrum as highly gifted. " Basically, our

theory really says that most autistic people or people with Asperger's

are savants, " says Kamila Markram. " But this is buried under social

withdrawal and fear of new environments. Their resistance to interaction

and fear may obscure the hypercapability that they have. It may well

turn out that successful treatments could expose truly capable and

highly gifted individuals. "

*Mental Health - Discover the latest research in our continuously

updated special

report <http://www.newscientist.com/channel/health/mental-health>*.

*The Human Brain - With one hundred billion nerve cells, the complexity

is mind-boggling. Learn more in our cutting edge special report

<http://www.newscientist.com/channel/health/brain>

Maia Szalavitz is a writer based in New York City

>From issue 2674 of New Scientist magazine, 19 September 2008, page 34-37

Autism basics

The autistic spectrum disorder (ASD) includes classical autism (now

known as autistic disorder), Asperger's syndrome (also known as

high-functioning autism) and a constellation of similar but somewhat

ill-defined conditions including Rett's syndrome, disintegrative

disorder and pervasive developmental disorder-not otherwise specified

(PDD-NOS).

Five leading theories of autism

*Weak central coherence*

Sees autism as a failure to integrate sensory information in a holistic

or " gestalt " manner.

*Executive function*

Impairment of the brain's frontal lobes causes loss of the top-down

" executive " controls which build the big picture at the expense of minutiae.

*Mind-blindness*

An underactive amygdala - a brain structure central to the processing of

emotional information, especially fear - leads to severe problems with

empathy and theory of mind.

*Extreme male brain*

An excess of testosterone during early development magnifies typical

male cognitive traits, such as systemising, at the expense of empathy,

sociability and other more typically " female " thinking styles.

*Intense world*

The new kid on the block. Proposes that the root cause of autism is a

supercharged brain (see main story).

Annie, who loves ya annie@...

--

" I know of nobody who is purely autistic or purely neurotypical. Even

God had some autistic moments, which is why the planets all spin " Jerry

Newport, a poet with Aspergers