Neuroscience and Autism

Brains that go bump in the night.

Brain science has come a long way in the last 200 years. We look back at the early efforts of the phrenologists to map personality, behaviour and mental abilities onto specific organs of the brain with amusement. But that is only because their methodology was so woefully inadequate. These brain organs were supposed to affect the contours  of the skull and a skilled phrenologist would take measurements of the skull and use his clinical judgement to interpret them in order to draw conclusions about a person’s character or mental capacities.

The early phrenologists relied upon post mortem studies of the brains and skulls of criminals and the insane. They were looking for things like the theft organ or the murder organ. Later the focus shifted to more generalized concepts, seeking organs for greed, jealousy, benevolence or self esteem.

Modern brain imaging techniques enable today’s neuroscientists to see the brain in action in living subjects. They have given us a detailed anatomical map of the brain and have been able to succesfully map particular functions to specific areas of the brain. Their results provide a more reliable guide to the workings of the human brain than the phrenologists ever could.

It is important to remember that, despite having access to so much more accurate data about the brain than the phrenologists ever had, we have not moved on that far in our ability to interpret the data. We are still ruled by the belief that specific parts of the brain are responsible for different types of behaviour. Sometimes this belief is well founded. Language areas, motor areas, the visual cortex; all have been reliably mapped.

Just as every sin contains the seed of its own salvation, so every virtue contains the seed of its own corruption. Success in  mapping so many functions onto specific areas of the brain has reinforced the belief that the determinants of all human behaviour can be located within specified areas of the brain. This takes us back beyond phrenology to Descartes and the dichotomy between body and soul. Just like phrenology, the Cartesian dualism of body and soul is another idea that has persisted beyond its time. Only now it refers to the biological determinism of the brain ruling the body; rather than the spirit being superior to the body.

Descartes also knew a thing or two that apear to have eluded modern reductionists in science. He did not regard the brain as the arbiter of all human behaviour, bodily passions could overrule the brain and lead us into irrational behaviour as well. This particular model of human behaviour as a struggle between higher mental function and lower animal instincts is no longer given scientific credence, though it persists in theology and some forms of Freudian psychiatry. But the principle that biofeedback mechanisms within ourselves as well as external pressures can act to modify behaviour is a necessary corrective to the belief that biological determinism begins and ends in our genes.

If we are a product of our brains, our brains are a product of our DNA.  There is a multi-million dollar research programme to discover the genes that cause autism. Strictly speaking, the genes do not cause autism. Researchers are looking for mutations in the genes that code for the proteins that build the parts of the brain that control the behaviours that are supposed to be impaired in autistic people.  But in the popular consciousness we have already had attempts to discover the Gay gene, the gene for aggression, etc. Media coverage of genes  and autism will inevitably reinforce the popular belief that genes code for behaviour.

Autism Under the Gyruscope

Never mind. The scientists know what they are looking for, don’t they? Well sort of. At one time scientists believed they had identified a part of the brain that plays a crucial role in face recognition. Attending to and remembering faces is a problem for many autistics. It is also a problem for me. So I have been following this research with some interest.

In 2001 Karen Pierce et al. published a paper, Face processing occurs outside the fusiform `face area’ in autism: evidence from functional MRI,  that showed that unlike non-autistic controls,

Overall results revealed either abnormally weak or no activation in FG [fusiform gyrus] in autistic patients, as well as significantly reduced activation in the inferior occipital gyrus, superior temporal sulcus and amygdala.

Again, quoting from the abstract,

Such a pattern of individual-specific, scattered activation seen in autistic patients in contrast to the highly consistent FG activation seen in normals, suggests that experiential factors do indeed play a role in the normal development of the FFA. [fusiform facial area]

The argument seems to be that autistic children spend less time looking at faces than normal children. So their FFA is impaired from under use. At the time this made perfect sense to me and encouraged me in my practise of teaching eye contact  and facial recognition to my autistic pupils. But according to Pierce the autistic adults in her study where just as good at the task as the control group. The abnormality was in the brain areas they used to perform the task. These adults had obviously trained themselves in facial processing. So why hadn’t their FFA kicked in when they did take an interest in faces?

This suggests that autistic brains have impaired or different wiring. But it does not explain why. The picture was further complicated when Geraldine Dawson reported that children took time to develop their fusiform gyrus but it was normally fully functional by age 12. Perhaps there is a window of opportunity when the FFA can be activated but once this has passed other pathways have to be utilized.

She showed pictures of cars and faces to 11 autistic adolescents and adults and to 10 age matched controls. In all of them the temporal inferior gyrus reacted normally, activating in response to the cars. It also activated in response to the faces in the autistic subjects. There was one anomaly. Autistic subjects did use their fusiform gyrus when looking at pictures of their mothers. I wrote at the time,

This suggests to me that (contrary to the popular belief that autistic aloofness arises from the fact that their brains are differently wired) intense emotional experiences may help to shape brain function. ACs have brains that can work in exactly the same way as their NT counterparts. The fact that they do not respond to everybody in the same way just goes to show that their brains are just far more discriminating in the range of stimuli and experience that shape their response. As ever with autism, the actual mechanisms are far more subtle than we first imagined.

I had no idea what I was talking about! I see echoes of Victor and Dr Itard in those “intense emotional experiences.” there are also dubious echoes of holding therapy, a misguided and dangerous attempt to force an emotional bond with the mother where none was presumed to exist. The truth is I could not explain the anomaly and was rather clumsily using it to make the point that we are a long way from fully understanding autism.

Rectifying the Anomaly

The one good thing about science is that scientists love an anomaly. If something blows a hole in the current theory, a good scientist will find it interesting and follow it up. As it happens I was not too wide of the mark with my guess that,

their brains are just far more discriminating in the range of stimuli and experience that shape their response.  

What if the fusiform gyrus is not an area for processing faces? What if everybody’s brains are more discriminating than we imagined? In this paper the fusiform gyrus and the inferior gyrus are both implicated in an expert object recognition pathway.

ABSTRACT

Brain imaging studies suggest that expert object recognition is a distinct visual skill, implemented by a dedicated anatomic pathway. Like all visual pathways, the expert recognition pathway begins with the early visual system (retina, LGN/SC, striate cortex). It is defined, however, by subsequent diffuse activation in the lateral occipital cortex (LOC), and sharp foci of activation in the fusiform gyrus and right inferior frontal gyrus. This pathway recognizes familiar objects from familiar viewpoints under familiar illumination. Significantly, it identifies objects at both the categorical and instance (subcategorical) levels, and these processes cannot be disassociated. This paper presents a four-stage functional model of the expert object recognition pathway, where each stage models one area of anatomic activation. It implements this model in an end-to-end computer vision system, and tests it on real images to provide feedback for the cognitive science and computer vision communities.

Expert object recognition? Perhaps the Fusiform Gyrus reacts to faces because most of us have an interest in faces and become quite expert at recognizing them. What if we became expert in something else. Would that light up the fusiform gyrus? Isabel Gauthier et al tested this by creating a set of novel objects called greebles and training volunteers to become greeble experts.

She concludes

The strongest interpretation suggested by our results together with previous work is that the face-selective area in the middle fusiform gyrus may be most appropriately described as a general substrate for subordinate-level discrimination that can be fine-tuned by experience with any object category.

One of Gauthier’s collaborators, Michael Tarr, has reported on similar research with extant experts and, just as with the Greebles, the fusiform gyrus is involved

Several of our findings speak directly to the question “Are faces special?” First, Greeble experts, but not Greeble novices, show behavioral effects – notably configural processing – that are often taken as markers for specialized face processing (Gauthier & Tarr, 1997; Gauthier et al., 1998). Second, Greeble experts, but not Greeble novices, show category-selectivity for Greebles in the right fusiform gyrus (Gauthier et al., 1999). Similarly, bird experts show category-selectivity for birds, but not cars, in the right fusiform, while car experts show category-selectivity for cars, but not birds (Gauthier et al., 2000). Reinforcing the generality of this result, chess experts, but not chess novices, likewise show category-selectivity in right fusiform for valid, but not invalid, chess game boards (Righi & Tarr, 2004). Third, across Greeble expertise training, subjects show a significant positive correlation between a behavioral measure of holistic processing (sensitivity to the presence of the correct parts for that object) and neural activity in the right fusiform (Gauthier & Tarr, 2002). Similarly, bird and car experts show a significant correlation between their relative expertise measured behaviorally (birds minus cars) and neural activity in the right fusiform (Gauthier et al., 2000). Behaviorally measured chess playing ability also shows a significant correlation with right fusiform response (Righi & Tarr, 2004). Fourth, the N170 potential (as measured by event-related potentials) shows face-like modulation in Greeble (Rossion et al., 2000), bird and dog experts (Tanaka & Curran, 2001), but only for a given expert’s domain of expertise.

So is the anomaly solved? Autistic children become experts on significant adults like mothers and thus arouse the fusiform gyrus when they see a picture of Mum. That still leaves open the question of why autistic children are not naturally interested in faces or social interaction to the same extent as their peers. Will the neuroscientists now go looking for the brain area that motivates us to become people experts? And when they find it how will they know it is the people area and not a different category of area that just motivates us to become experts?

It would be really nice if all those parents that yearn for some acknowledgement of affection from their autistic children could be shown an fMRI scan of their child’s fusiform gyrus lighting up when they walk in the room.

A tale of two autisms

The Sunday Times has published a thoughtful piece on autism by Mark Henderson, entitled ‘We ask ourselves, can we separate Alex and autism?’ 

Alex is 12 years old and described as being “at the less extreme end of the autistic spectrum.” This was not always the case. He regressed when he was 14 months old, losing speech and becoming so withdrawn that nursery staff thought he was deaf. Reading his mother’s description of his early years Alex’s autism is plain to see. But he had to wait til he was 5 to get a diagnosis. Julia, his mum, would welcome improvements in genetic screening if it meant that children like Alex did not have to wait so long for a diagnosis but some of her worries chime with those raised by Dr Russell that are discussed on my previous blog.

“It took an age to get Alex the help he needed,” she said. “The earlier you know, the better, and if this could help us identify autism as young as possible it would be wonderful.

“But I would not want a situation like Down’s syndrome, where you tell parents while the child’s in the womb and you have to make a decision.

“We also ask ourselves how much of Alex’s personality is Alex, and how much is the autism. Can we even separate the two?

“If you asked us could we have prevented it, we would have to think. Obviously in some ways it would be better for him, but he is happy in himself.”

Questions like these are bound to come up more often as advances in genetic research offer the prospect of earlier diagnosis and even the possibility of prevention or cure. Whether or not these possibilities ever materialize is not the point. But they are undoubtedly powerful levers for releasing the massive funds that genetic research consumes.

[NB. research costs may be massive in relation to the biological sciences. But they are still small by comparison to the costs incurred in particle physics.  The Large Hadron Collider at Cern is costing in excess of 4 thousand million USD. Michael Wigler at Cold Springs Harbor has a budget of 14 million USD for his research programme into autism.]

The hype that surrounds genetic research is often encouraged by scientists eager to claim their portion of the research pie. This makes it even more important that journalists approach the topic dispassionately and are sensible to the dangers that Dr Russell raised in her article for Communication.

So it was a pity to read Mark Henderson’s latest offering in the Times, Hunting the gene that traps children in their own world which proclaims that

Parents and scientists are hoping that a new detailed analysis based on human genome will bring a big breakthrough within a year.

in the space of 4 paragraphs we get the following [emphasis added]

one of the most controversial and feared medical diagnoses of modern times

but it prompted thousands of parents to agonise over the cruel condition that seems to leave children walled off in a social and emotional world of their own, apparently beyond their love.

A disorder that was once rare has become alarmingly common,

the condition retains a brutal mystery.

This is exactly the sort of language that fuels fears about autism. It suggests that research into the prevention and cure of autism is almost an obligation. Those of us who argue for autism acceptance are accused of wishing a nightmare disorder on children. But children like Alex know happiness. They are not beyond love. They have a future. Or at least they might have a future if they are seen as people who can prosper with help and understanding, rather than the victims of a brutal mystery, at best to pitied, at worst to be feared.

All this is merely the preamble to a story about some research that is not even finished yet!

Within the next year a new study is expected to identify many of the genes that underlie autism for the first time.

I am always suspicious of claims made for a study that is still in progress. This is hype. And we have heard it many times before.  My thanks to Michelle Dawson for reminding me that in February, 2004  Thomas Insel of the NIMH said this about autism in the New York Times

“My sense is that we are close to the tipping point in this illness, and that over the next couple of years we will have, not all of the genes, but many of the genes that contribute.”

Funnily enough, we are at the same tipping point three and a half years later.

The medics tell me we are at a tipping point,” said Dame Stephanie Shirley, the millionaire computer entrepreneur and philanthropist, who is the chairman of the research charity Autism Speaks and the mother of an autistic son.

My guess is that researchers always feel as though they are on the brink of a fantastic new discovery. That is what sustains them through the painstaking daily grind at the lab bench or crunching data in front of a computer screen.  But the rest of us would rather wait for the results before we get too excited.

The article ends with another quote from Dame Shirley.

“It is quite possible that in five to ten years, we will have a real understanding of this disorder,” she said. “That’s a timescale that means today’s children may be helped.”  

I am sure that Dame Shirley is already doing a lot to help her autistic son. But genetics is the science de jour. There is a popular belief that all behaviour is the product of specific brain areas that in turn are the product of the DNA code carried in our genes. Unlock the genetic code that governs our brains and we can manage our minds. We have been here before.

Once upon a time psychoanalysis was supposed to have all the answers. It gave way to behavioural science. New brain scanning technology marked the rise of cognitive neuroscience. Genetics is currently in the ascendency. Will it prove more productive than previous paradigms or do we need a new way of trying to grasp the reality of what it means to be human, maybe one that includes autism rather than trying to eliminate it? It is significant that all the genetic research so far has tried to identify genes associated with the deficits and impairments associated with autism. Nobody to my knowledge is trying to identify the genes responsible for the autistic strengths identified by researchers like Mottron and Gernsbacher.

I do not have a crystal ball. For what it is worth, in my opinion genetic research will expand our knowledge and our understanding. But it will not lead to any sort of a cure or an end to autism. Given our current level of knowledge that is probably for the best.

Autism, Genetics and Research Ethics

The latest edition of Communication, the members magazine of the National Autistic Society contains two interesting articles on genetic research.

GENE GENIE by Professor Anthony Bailey

The first  article, by Professor Anthony Bailey of Oxford University’s Autism Research Unit, seeks to summarize recent developments in genetic research. Considering the complexity of the subject and the nature of his audience (mainly parent members of the NAS like myself with no specialist scientific training) he does a remarkable job in under a 1000 words. I  find that those experts who can write coherent and concise accounts of their work for a lay audience are usually the ones with the soundest grasp of their subject matter. Professor Bailey is no exception.

He starts by emphasizing how little we know.  This cannot be stressed too much. There have been a spate of recent reports in which journalists, and some scientists who ought to know better, have hyped up the latest genetic “breakthroughs” as harbingers of an imminent cure. But all we have so far are “candidate” genes. This is not to diminish the work of the scientists involved. Genetic research has been marked by a massive collaboration of scientific and funding institutions. It is detailed and difficult work that is only now beginning to accelerate with access to improved technology.

The most likely candidates are genes on the long arm of chromosome 7 and on chromosome 2. Again, caution is necessary. These are not genes for autism. They are potential genes for autism susceptibility. There is no single gene for autism. According to Professor Bailey, “the risk of developing autism seems to be conferred by the interaction between at least 3 or 4 genes (and possibly many more) and there were no clues as to what these genes might code for.”

When a gene is finally identified scientists will still want to learn more about what it does, when it is expressed and which other genes it interacts with. They will also try and identify the environmental factors at work. These factors need not be “known neurotoxins.” They may be neutral or even beneficial in the absence of particular genetic combinations.

[OK I realize that some of my readers may regard autism as a beneficial outcome. I look forward to your comments so that we can explore the nuances of meaning around accepting autism and welcoming autism.]

Our knowledge of genetic factors in autism leans heavily on work with families where more than one sibling is affected.  The evidence from twin studies is that autism is a highly heritable condition. So it makes sense to look at families where this is most obviously the case when seeking the genetic causes of autism. But many parents who read Professor Bailey’s article will have no obvious genetic traits of autism in their families. A new study may help to explain this. Dr Michael Wigler is a molecular geneticist at Cold Spring Harbor Laboraory in New York and he has just published a pilot study suggesting that spontaneous mutations in the parents’ sperm or egg cells may be the cause of autism in a majority of cases. Prometheus discusses this in more detail on his blog, Photon in the Darkness, and provides a link to Dr Wigler’s paper.

This all goes to show how complex the science is. It is increasingly unlikely that we will find a simple genetic cause or even a simple genetic predisposition that relies on an obvious and preventable environmental trigger for autism. I am fascinated by the science of autism but it is not going to provide any immediate answers or easy fixes. Social policy will have a greater impact on the quality of life for autistic people in the foreseeable future. This is why public attitudes to autism are so important – a point addressed in the second article.

CHOOSING THE FUTURE by Dr. Phiippa Russell

Dr Russell is a Disability Rights Commissioner and Disability Policy Advisor to the National Childen’s Bureau. She wrote about the ethical implications for genetic testing and research. She began by pointing out that alongside the potential health benefits of genetic science there is also the danger that “the primary focus of new genetic technology might not be on improving the quality of life and healthcare for vulnerable individuals. Instead, it could be lead to eugenic attitudes, which devalue disabled people and encourage discrimination in employment and other areas of life.”

There are some areas where genetic screening ought to be non-controversial. But what if it leads to discrimination in obtaining employment or essential life insurance? Dr Russell has an interesting take on this. She argues that women with a known genetic susceptibility to breast cancer may acually live longer than other women who are less likely to have regular mammograms and more likely to have their cancer detected later, when treatment options are less effective.

This kind of logic may appeal to actuaries. But most people will react negatively to the idea of disability, especially if it is a genetic disability that is  predictable and, disregarding David Hume,  therefore ought to be prevented. Dr Russell thinks that “If we accept this view, then we risk

• reducing embryos, foetuses and, in consequence, individuals to their genetic characteristics, thereby reversing the progress made concerning human and civil rights for disabled people
• increasing responsibility (and social exclusion) for familes with disabled children, where the disability was related to genetic predisposition
• ignoring the multiple talents of disabled people and the real contribution which they make to family and society.”

Genetic science will advance, regardless of the ethical dilemmas it creates. People with disabilities ought to benefit from these advances. But according to Dr Russell “there are challenges in avoiding unnecessarily negative pictures of quality of life and value to the local community. “

She does not mention autism by name but goes on to say, “Many readers will be both aware and proud of their disability. It is unique to them and carries benefits as well as some challenges.”

Dr Russell ends with his quote from an unidentified disabled man.

“Disabled people themselves must join the debate about the ethics of genetic testing – you cannot close Pandora’s box once it has been opened, but the challenge is in using new information proactively to improve quality of life, not to shut down someone’s work and other opportunities because of poor understanding and low expectations. Knowledge is power – but it is essential that it is controlled by the person directly affected and used for his or her benefit, rather than used by others as a means of social exclusion.”

This is one reason why next month’s meeting on the Politics of Autism is so important. Anyone who can attend should ring up and book a place now.

According to Communication “The NAS is keen to hear the views of members and others on this complex issue … email communication@nas.org.uk with the words ‘gene ethics’ in the subject line.” The full articles in Communication are only available to NAS members.  If you want to join email membership@nas.org.uk

I am greatly encouraged by the NAS  inviting this sort of debate. I do urge people to respond.

Downs but not out.

Down’s syndrome novel tugs at America’s heartstrings

Moving tale that highlights genetic condition becomes sleeper hit of the year

Paul Harris in New York
Sunday June 17, 2007
The Observer

Like many good stories, The Memory Keeper’s Daughter begins on a dark and snowy night. But, unlike most first novels from barely known authors, the book has gone on to be one of the biggest hits in recent American publishing. It has sold more than 3.5 million copies in America and is due for publication in at least 15 other countries. It has done all this despite – or perhaps because – it is about one of the most emotional and difficult situations any new parents might face: a child being born with Down’s syndrome.

According to the Observer

The book has been a huge hit among parents of Down’s children and those who work with them. They have praised its portrayal of a child leading a full life and bringing happiness to a parent.

This is all very positive but I wonder, if the writer had interviewed people with Downs, would they have praised it because it portrayed a child with Downs bringing happiness to a parent? I have always found that the joy of parenthood derives from bringing happiness to my children. Perhaps this is what the writer meant, that parents can rejoice in their children’s happiness.

Apparently many prospective parents of Downs children do not believe that their child will be happy.  Over 90 per cent of Downs fetuses that are identified by prenatal screening are aborted. The UK Downs Syndrome Association estimates that 10 in 10,000 live births are Downs. Earlier estimates, before amniocentesis became common, ranged from 15 to 24 in 10,000.

The relevance to autism

With Downs we know exactly where the genetic abnormality lies but have no idea why one of the parents produces a sperm or egg cell with an extra chromosome. We do not understand how this extra chromsome works to produce the features of Downs Syndrome and nearly 50 years after Professor LeJuene discovered the trisomy on chromosome 21 we are still a long way off being able to reverse or ameliorate its effects. All we can do is identify around a half of Downs pregnancies and offer an abortion.

A lot of money is being spent on research into genetic markers for autism. There is not just one, there are dozens of candidate genes for autism and, unlike Downs which is present from conception, there are as yet unknown environmental factors which may contribute to gene expression. Yet every discovery is trumpeted as leading to a possible cure or a genetic test to prevent autistic babies from being born.

This is damaging for a number of reasons.

1. If a cure is thought to be just a few decades away this will divert funding way from research into ways of improving outcomes for people who are already autistic.
2. To justify the huge expenditure autism has to be hyped as a health crisis that is devastating lives, when in fact it is lack of understanding and the irrational fears that this sort of hype encourages that are the biggest obstacles for many families.
3. If autism is so unremittingly awful and the genetic solution is hyped as twenty years down the line parents of newly diagnosed children are going to be vulnerable to the biomedical quackery that is already entrenched among some sections of parents.
4. Existing autistics will be viewed at best as victims and not as human beings with equal rights to acceptance and ethical treatment.

As public opinion increasingly lines up behind scientific opinion on the unfeasibility of the autism vaccine hypothesis it is important that we speak up for autism acceptance and challenge the triumphalism in those quarters of the mainstream medical and scientific research community that seek to eliminate diversity.