Most Autistic People Have Normal Brain Anatomy

By Neuroskeptic | October 25, 2014 12:54 pm

A new paper threatens to turn the world of autism neuroscience upside down. Its title is Anatomical Abnormalities in Autism?, and it claims that, well, there aren’t very many.

autism_difference

Published in Cerebral Cortex by Israeli researchers Shlomi Haar and colleagues, the new research reports that there are virtually no differences in brain anatomy between people with autism and those without.

What makes Haar et al.’s essentially negative claims so powerful is that their study had a huge sample size: they included structural MRI scans from 539 people diagnosed with high-functioning autism spectrum disorder (ASD) and 573 controls. This makes the paper an order of magnitude bigger than a typical structural MRI anatomy study in this field. The age range was 6 to 35.

The scans came from the public Autism Brain Imaging Data Exchange (ABIDE) database, a data sharing initiative which pools scans from 18 different neuroimaging centers. Haar et al. examined the neuroanatomy of the cases and controls using the popular FreeSurfer software package.

What did they find? Well… not much. First off, the ASD group had no differences in overall brain size (intracranial volume). Nor were there any group differences in the volumes of most brain areas; the only significant finding here was an increased ventricle volume in the ASD group, but even this had a small effect size (d = 0.34). Enlarged ventricles is not specific to ASD by any means – the same thing has been reported in schizophrenia, dementia, and many other brain disorders.

Here’s some of the data: each double bunch of dots represents one of the research sites, with grey being the autistic brains and black the controls. Each row contains the data from one part of the brain. You can see that there’s just not much difference. While a few sites find differences in a few measures, they’re not consistent across sites. Only ventricle volume (bottom row) is different overall.

dinstein_montage

A detailed cortical morphometry analysis of the brains did find a few statistically significant results in cortical thickness, but not other metrics:

Individuals with ASD exhibited significantly thicker cortex than controls in several areas including the right and left occipital poles, left middle occipital sulcus, left occipital-temporal sulcus… [however] there were no significant differences in volumetric or surface area measures between groups. There were also no significant volumetric differences between groups in any of the subcortical areas.

But even these differences was small. Using a machine learning technique called linear discriminant analysis, Haar et al. attempted to distinguish between the ASD and control brains on the basis of neuroanatomy. They did this in a number of different ways. The best performance was 60% – better than nothing, but very modest. And this was the best result: using other analysis options, the performance was closer to 50% – which is no better than flipping a coin.

Worryingly, Haar et al. show that the ‘accuracy’ of this analysis could be increased by lowering the sample size. They generated random subsets of their data-set and tested the same discriminant analysis on these artificial small samples. They report that “Around 30% of the randomly selected groups containing 20 subjects in each group exhibited decoding accuracies over 60%.” – which raises the possibility that previous reports of highly accurate ASD ‘diagnosis’ on the basis of brain structure, were false positives caused by small samples.

Haar et al. conclude that:

There was no evidence for between-group differences in any measures of gross anatomy or in specific brain regions including the amygdala, hippocampus, most segments of the corpus callosum, and the cerebellum, which have been implicated in previous anatomical studies of ASD.

These results suggest that many of the previously reported anatomical abnormalities are likely to be of low scientific and clinical significance… anatomical differences between high-functioning ASD and control groups (aged 6 – 35 years old) are very small in comparison to large within-group variability.

This suggests that anatomical measures alone are likely to be of low scientific and clinical significance for identifying children, adolescents, and adults with ASD or for elucidating their neuropathology.

I think this is an important paper and one that the autism field will need to take very seriously. There are hundreds of studies claiming to have found differences in brain structure in autism, many with small sample sizes, and Haar et al’s failure to replicate almost any of these claims, is sobering. It’s important to remember, however, that this paper only considered brain anatomy. It doesn’t contradict studies looking at brain function, nor does it relate to microanatomy or neuropathology (i.e. microscope work.)

As far as it goes, though, it’s a bit of an earthquake – and I’m not sure how much of the field is left standing.

ResearchBlogging.orgHaar S, Berman S, Behrmann M, & Dinstein I (2014). Anatomical Abnormalities in Autism? Cerebral Cortex (New York, N.Y. : 1991) PMID: 25316335

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  • http://bit.ly/ppaulojrprof Pedro Paulo Oliveira Jr

    We are one of those 180 groups that published works finding differences, we used FreeSurfer too. http://www.sciencedirect.com/science/article/pii/S0022395612003597

    I think this study is interesting although I don’t see some questions I would make as a peer-reviewer answered there, some examples below:

    – Which version of FreeSurfer they used? (I know that my own group did not disclosed that too in our paper) but there’s one version in the 5.x range that’s a no-go and that has been disclosed in the FreeSurfer discussion list. I never saw any e-mail from the authors in the list.

    – They ran the FreeSurfer pipeline with or without manual intervention?

    Fortunately, however, automated estimations of cortical and subcortical volumes with Freesurfer have been shown to be remarkably robust across MRI scanners of different manufacturers (varying by 0–3%) as long as the field strength is kept constant at 3T

    I agree with that after my personal experience processing thousands of datasets with FreeSurfer, however that citation quoted is about some specific brain regions using only healthy volunteers (5 in the case of 3T equipment).

    I believe this paper from Haar at al. is very important on the subject and it’s a shame that some important unanswered questions could cast some shadow of confusion in the paper in question.

    Other people with experience with FreeSurfer may have some questions too.

    • ChrisLong1980

      You all may be looking in the wrong place. Look at the neuro-glial relationship, and see what you find.

    • http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

      Thanks – these are all important points. FreeSurfer version is known to influence cortical morphometry estimates.

  • http://dachte.org Pat Gunn

    If you have hundreds of studies on one side, and one study on the other, you probably shouldn’t bet on the one study to be an earthquake in the field. Most of the time, the one study is off somehow.

    • BrittanyWinters8

      But the hundreds of studies do not generally back each other up–mostly they merely report some brand new putative anatomical difference between autists and normals. And in so doing, they used a far smaller sample size than the new study–small sample size being a huge red flag. Moreover, they were able to get published despite this statistical shoddiness only because they found a positive effect, possibly after fishing around in their data.

      By contrast, this study is a large-scale re-examination of a whole lot of these specific hypotheses, which was going to publishable (and published) regardless of its outcome.

      Think of it like a high quality financial audit. If you are statistically shrewd you will put your money on this one, not on any or all of the others. The large number of these other studies is more a sign of crappiness than validity.

      Similar situation exists in dietary supplements, where each of the supplements that has been found worthless in large-scale high-quality RCTs was the topic of a whole literature seemingly little positive studies. Google lit on ginkgo biloba, echinacea, saw palmetto, etc etc.

      • http://dachte.org Pat Gunn

        Whether that’s true or not, we at least should wait for this to be reproduced via other teams, or at least wait a bit to see what the responses look like. One study this year that aims to upset results of many studies from years past is not good enough. I think the smart bet, at least for now, is against this conclusion.

      • http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

        Exactly – it’s not as if the small studies all agreed with each other about specific abnormalities. They found different abnormalities. Some have replicated a few times, but none were reliable.

        • http://petrossa.me/ petrossa

          which makes my point pretty convincing. You’d exactly expect that from a mixed group of various afflictions

        • Bill C

          Thank you, I was going to ask.

  • Brenda Waddell

    um…er…it is not the brain..you silly researchers..it is the chemicals supplied to the brain..the body is not producing these chemicals correctly and thus the brain does not receive the appropriate amount..there you go..now go research some more..hint check out the liver

    • theLaplaceDemon

      what specific chemicals?

    • Benjamin

      Thank you I’m sure you already know how Autism works, we will immediately stop funding all other research paths and focus entirely on liver-derived ‘chemicals.’

      • Brenda Waddell

        i do know…it is chemical.. what mr.smarty pants do you think it is? lol…a brain difference? an evil witch cast a spell? lol it is either chemical or electrical..and it is not electrial.. you figure it out

        • Emkay

          correct…. your body is a chemical plant down to the cellular level… for certain..

        • zanzibar55

          The fact that they do not find gross anatomical differences in the brain does not mean that there are no “electrical” differences or that connectivity is not impaired.

          Surely peripheral substances may play a role, but saying that autism is a liver disorder is just obvious trolling.

    • shayneo

      Dunning Krueger is a hell of a drug.

  • AnOski

    I don’t get what the author of this blog is trying to do.

    Statements from the academic paper:

    >Individuals with ASD exhibited significantly thicker cortex than controls in several areas including the right and left occipital poles, left middle occipital sulcus, left occipital-temporal sulcus…

    >an increased ventricle volume in the ASD group (Paraphrased, per article)

    Whereas the author of *this blog* seems set on playing down the differences:

    >But even these differences was small. (sic)

    >even this had a small effect size (d = 0.34)

    FYI, a d value of 0.34 is a significant effect, and it doesn’t speak to the magnitude of the cranial volume differences observed.

    If you’re going to write “about a paper,” don’t try to belittle its conclusions to prove your own point, whatever it might be.

    • Metalhead Nick

      He’s not belittling the paper at all. The point of the paper is that there are no real differences between the brains of people with autism and the brains of others. It does not reall matter whether or not the d value of the ventricle size is small or significant. Increased ventricle size is correlated with a host of others conditions rendering it inadiquate to determine whether someone has autism or not. That said, I am curious about the thickened cortex as well. Maybe is missed it but does the thickened cortex correlate with area, that seems like it might be interesting.

      • AnOski

        See my above reply. In particular — this study focused on “high-functioning individuals with IQ >70).” In other words, they’re selecting for normalcy. Your statement appears to apply this conclusion to all people across the S of ASD, so to speak. That probably isn’t a good idea, IMO.

        The rest of it’s relevant too, esp. with regards to the disorder(s) being due to the expression of multiple genes. You would expect to see larger brain changes with increasing severity of ASD, so high-functioning ‘S’ subjects is likely to show you a variety of ‘minor’ genetic issues, with different expressions. More severe cases are more likely to converge in both symptoms and expression as would be visible in an MRI — e.g. with overlapping genetic issues.

        • Metalhead Nick

          Yeah, I agree with that. I wondered about just using high functioning people with ASD. I suppose in their defense one could say it’s easier to distinguish those with more serious cases and therefore the focus was on early (I guess) detection of higher functioning individuals as it would be harder to diagnose them. It would be more interesting to include medium level and lower functioning individuals to see if there are particular trends. I know that sounds kind of silly, but the real weight behind the article is the large sample size. I wonder if they used a large enough sample size for various levels of individuals with ASD what they might find. It highlights the problem of false positives with low sample sizes, but only carries out analysis on high functioning individuals. I’m also still curious about the thickened cortex. But yeah you are right, one would kind of expect that higher functionality would correlate with more normal brain structure…

          • AnOski

            >It would be more interesting to include medium level and lower functioning individuals to see if there are particular trends.

            Definitely.

            >I know that sounds kind of silly, but the real weight behind the article is the large sample size. I wonder if they used a large enough sample size for various levels of individuals with ASD what they might find.

            And I wonder if they stopped to ponder whether or not it made sense for all who show symptoms of ASD to exhibit the same physical brain anomalies, etc. Especially given what we know about its range of severity, differences in symptomatic expression, etc.

            >It highlights the problem of false positives with low sample sizes, but only carries out analysis on high functioning individuals.

            I’m not so sure this is the right way to look at it. You could call the subjects “high-functioning ASD” persons or “people who fall in in the lower 2-3% of a distribution of IQs.”

            Since “ASD” is kind of a blanket term, it loses its meaning when you approach normalcy. Maybe these people have other issues, or they are simply of unusually low intelligence. My soft major as an undergraduate was psychology, and…diagnoses are just that. A best fit.

            >I’m also still curious about the thickened cortex. But yeah you are right, one would kind of expect that higher functionality would correlate with more normal brain structure…

            Thickened cortex? There are a few genes for that 😉

          • Metalhead Nick

            Yeah I meant high functioning people with ASD. You sort of touch on it, but as people approach “normalcy” you suggest maybe they could be something other than autistic, autism being the best fit…I was a philosophy major myself, so I really just dabble in all the sciences so I could be way off here but I’ve wondered if perhaps we are all just on the autistic spectrum, ie that all it is is a spectrum. Like how a lot of mathematical savants claim to see the numbers as shapes or colors. Normal people see number lines to varying degrees. I don’t know where exactly I’m going with this, but line drawing on a spectrum is a difference of quantity not quality. But people do like line drawing and it really only becomes contentious when you approach the line. Like where dinosaurs end and birds begin. It’s easy to distinguish a stegosaur as not a bird, but why archeoptryx and not microraptor or the other various feathered, winged, volant dinosaurs? I’m probably way of here…

          • Metalhead Nick

            Maybe this is better. If high functioning autistic people have roughly normal brains and can function at a relatively normal level, the changes in gross brain structure becoming more apparent as you get further down the autistic spectrum, and often coinciding with other conditions, then perhaps “autism” really is just a catch all. Like a naturalist’s waste basket taxon. So anyone with a mental retardation that does not have Down syndrome or some other definitely condition is “autistic”. I suppose this could create a spectrum effect as individuals are really being grouped by their distance from the norm. Or maybe not.

          • http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

            That’s an interesting suggestion; but most folks who work with low functioning people say that some of them are clearly ASD and some are not. The ADOS diagnostic interview has detailed protocols for making a diagnosis of ASD even in people who have no speech.

          • AnOski

            >most folks who work with low functioning people say that some of them are clearly ASD and some are not.

            You’re appealing to a biased authority — in this case, people who have been taught what is “ASD” and what isn’t from symptomology, regardless of genetic/neurological differences, etc.

            >The ADOS diagnostic interview has detailed protocols for making a diagnosis of ASD even in people who have no speech.

            And the same problem persists there. The ADOS diagnostic interview doesn’t include MRIs or gene sequencing. Just symptoms, etc.

          • Savage

            Yes… because that is all we have for diagnostics criteria at this point. As we unravel the secrets of the genome and the brain, we will begin to understand and be able to test, IN UTERO for the distinguishing characteristics…

            The biggest thing, however, is early detection and skill training for the parents… if there is someone there to help with the issues and teach the proper social skills, Most Autistic Spectrum Individuals can flourish

          • AnOski

            >Yes… because that is all we have for diagnostics criteria at this point.

            That’s not remotely true. Give them all MRIs and see how their brains are actually different.

            >As we unravel the secrets of the genome and the brain, we will begin to understand and be able to test, IN UTERO for the distinguishing characteristics…

            With psychologists? No. Genetically? Sure, but we’re still going to need to pin down the genes. Either way, the psychologists of today aren’t qualified for that kind of work.

            >The biggest thing, however, is early detection and skill training for the parents…

            I disagree. The biggest thing is figuring out what goes wrong in prenatal development so that we can treat these people before they develop their disorders. Stop trying to treat the symptoms after the fact.

            >if there is someone there to help with the issues and teach the proper social skills, Most Autistic Spectrum Individuals can flourish

            They can kind of function in normal society if they try really hard. A few exceptional examples do quite well for themselves. They are the *extreme* minority.

          • Savage

            ACTUALLY… we are finding new things that can EVENTUALLY be used for diagnosis, but the studies show a link, but not CONCLUSIVELY that this is present in all autistic spectrum individuals (two studies does not a scientific proof make)…

            We are a LONG way from these hallmarks that denote autistic spectrum disorders being included in the DSM or the ICD. So… AT THIS POINT, the ONLY recognized diagnostic criteria for Autistic Spectrum Disorders are observational and behavioral.

            Disagree all you want… As one of THESE people, I take your opinion on the biggest problem with and facing Autistic Spectrum Disorders and I choose to go with my own experiences, the experiences and communities of people like me… And point out that the extreme minority are those who cannot be functional in society.

            Please don’t help us… you don’t understand what it is to be us.

          • AnOski

            >ACTUALLY… we are finding new things that can EVENTUALLY be used for diagnosis,

            Define “we.”

            >but the studies show a link, but not CONCLUSIVELY that this is present in all autistic spectrum individuals (two studies does not a scientific proof make)…

            No they don’t. These studies show that the symptoms psychologists have been calling “ASD” don’t correlate with actual brain morphology. It’s a hodgpodge of issues all lumped into a single term.

            >We are a LONG way from these hallmarks that denote autistic spectrum disorders being included in the DSM or the ICD.

            ASD is in the DSM. Thanks to people like you. It’s “a disease” and we don’t even know what it is — just how to diagnose it.

            http://www.autismspeaks.org/what-autism/diagnosis/dsm-5-diagnostic-criteria

            >So… AT THIS POINT, the ONLY recognized diagnostic criteria for Autistic Spectrum Disorders are observational and behavioral.

            Right. It’s like classifying animals based on their behavior, and not their actual physical characteristics.

            “Is it a cat?”

            “It acts like a cat.”

            “Therefore, it’s a cat.”

            [It’s actually a shiba inu. Or a ferret. Or something else.]

            >Disagree all you want… As one of THESE people, I take your opinion on the biggest problem with and facing Autistic Spectrum Disorders and I choose to go with my own experiences, the experiences and communities of people like me…

            Oh, you’re pulling the “appeal to authority” fallacy card out. I choose to go with the neuroscience literature.

            FYI, your personal experiences don’t make you any more qualified than someone like me, educated as a psychologist, or an expert researcher. Check out the literature.

            >And point out that the extreme minority are those who cannot be functional in society.

            Depends on what “ASD” is. You’d like it to be an inclusive definition, but you’re choosing to disregard relevant scientific literature to make that point. You’re not saying “we need to understand it.” You’re saying “some people act atypically sometimes and they should all be called ASD because….no good reason.”

            >Please don’t help us… you don’t understand what it is to be us.

            You might as well walk into a hospital and say “you don’t understand what it’s like to have this illness.” You understand how whatever it is you have affects you, but you don’t understand what you have. What you are.

            And the strange thing is that you think you have it all figured out. The relevant literature (like this paper) clearly shows that there’s more going on.

          • Savage

            Define “we.” <– humans

            These studies show that the symptoms psychologists have been calling "ASD" don't correlate with actual brain morphology. <– Actually… ongoing studies are showing that the extra synapses and differential nerve trunk paths are present in almost all Autistic Spectrum Individuals… They are showing that there is an actual background reason for it.

            "Thanks to people like you. " <– Thanks to people like me? Autistic spectrum individuals? This was clearly intended as an insult. I am not a psychiatrist, nor do I work for the NIMH, so I have no input into what does and does not go into the DSM. If my input was heeded, Asperger's syndrome would not have been eliminated from the DSM-V.

            I am not going to go through your entire post like this… but your analogy is flawed. You stated I might as well go to the hospital and say, blah, blah, blah…

            I am saying don't help because you are arguing with one of us and telling me how I should think or feel about my condition. You bash and belittle, but I have researched, discussed, argued, conducted polls… I write a successful autism self advocacy blog… And I receive constant letters and comments that tell me how spot on I am. So… telling me that I am wrong about the intellectual implications is a waste of your time and mine.

            Telling me that I am wrong about the research when I have read (to date) 1247 studies about my condition, have been one of the people who submitted themselves for synapse analysis and high definition fiber tracking, spent the last 30 years of my life talking to every scientist I can find who studies my condition is also a waste of your time and mine.

            In closing… here's the definition of disease… it fits. Just because you have a knee jerk reaction to it, doesn't change that. And if we do not have a disease, then there is no need for accommodations, treatments or even research, because there's nothing wrong with us. We can't have it both ways.

            disease /dis·ease/ (dĭ-zēz´) any deviation from or interruption of the normal structure or function of any bodypart, organ, or system that is manifested by a characteristic set of symptoms and signs and whose etiology,pathology, and prognosis may be known or unknown.

            I can glean from your stance that you have a loved one that has been diagnosed, possibly recently… And I am sorry that is the case, and if I am wrong about that, so be it. But be wary of avoiding certain words… the pitfalls of excessive self esteem in Autistic Spectrum Individuals are manifold.

            If you are interested, I can link you to my blog and you can see a lot of what I am talking about. If not, that's fine… I'm done arguing with you … I do want you to know however, there is a HUGE contingent of us that say "Autism Speaks doesn't speak for me."

          • AnOski

            You apparently flagged my original response. Fortunately, the bulk of it was still saved.

            >Define “we.” These studies show that the symptoms psychologists have been calling “ASD” don’t correlate with actual brain morphology. They are showing that there is an actual background reason for it.

            Genes are presumably responsible for the differences you claim exist, as well as those noted in the above article.

            >”Thanks to people like you. ” This was clearly intended as an insult.

            Yes, it was. You’re ignoring a heck of a lot of accepted, peer-reviewed work in neuroscience to make the claims you’re making.

            >I am not a psychiatrist, nor do I work for the NIMH, so I have no input into what does and does not go into the DSM. If my input was heeded, Asperger’s syndrome would not have been eliminated from the DSM-V.

            Right. “People like you” who want to label introverts as people with diagnosable, medicable, psychological disorders.

            >I am not going to go through your entire post like this… but your analogy is flawed. You stated I might as well go to the hospital and say, blah, blah, blah…

            The analogy holds. You don’t seem to understand neuroscience or the importance it has for understanding neurological abnormalities. Giving a wide range of symptoms a name like “aspergers” when you don’t understand what it is, or even if it’s a tangible thing, is backwards.

            >I am saying don’t help because you are arguing with one of us and telling me how I should think or feel about my condition.

            Right. And some people use homeopathy to treat their conditions. That’s all they want to do.
            Is it because they don’t understand what’s wrong with them? That’s probably part of it. You’re ignoring a vast body of accepted work, just as they do.

            >You bash and belittle, but I have researched, discussed, argued, conducted polls…

            Again the appeal to authority. Your supposed qualifications seem moot when paired with the willfully ignorant statements you’re making. To say nothing of my own qualifications.

            >I write a successful autism self advocacy blog…

            Oh, you’re a blogger. You must know everything about the subject. More than someone who holds a degree in psychology from an R1 institution, who studied it for years.

            >And I receive constant letters and comments that tell me how spot on I am.

            People sympathize with you? You must be right! Lol.

            Here:

            http://en.wikipedia.org/wiki/Argument_from_authority

            http://en.wikipedia.org/wiki/Argumentum_ad_populum

            >So… telling me that I am wrong about the intellectual implications is a waste of your time and mine.

            Right. Because your only justification for your beliefs are textbook logical fallacies.

            >Telling me that I am wrong about the research when I have read (to date) 1247 studies about my condition,

            Oh, please. You’ve apparently ignored some important ones.

            http://informahealthcare.com/doi/abs/10.3109/13682828909011951

            http://www.annualreviews.org/doi/abs/10.1146/annurev.genom.5.061903.180050

            http://link.springer.com/article/10.1007/s10803-004-1038-2#page-1

            Etc.

            If you don’t read critically, and instead selectively prune from papers to support your bias, it doesn’t count for much.

            [The same goes for flagging comments with which you disagree.]

            >have been one of the people who submitted themselves for synapse analysis and high definition fiber tracking,

            Now you’re qualified because you volunteered for a study? I did quite a few sit-in studies as an undergrad. I wonder what expertise I picked up without realizing it.

            >spent the last 30 years of my life talking to every scientist I can find who studies my condition is also a waste of your time and mine.

            “I spoke to lots of people about this: therefore, I am an expert.”

            Right.

            >In closing… here’s the definition of disease… it fits.

            What fits? The symptoms necessary for diagnosis? They change yearly. The severity needed for diagnosis? Also changes with each DSM. The cause(s) of the “disease(s)?” Not well understood, possibly not related beyond being “genetic” disorders.

            >Just because you have a knee jerk reaction to it, doesn’t change that.

            Wow. If anyone’s having an unjustified reaction to a comment here, it’s you. Way to pass the buck, bucko.

            >And if we do not have a disease, then there is no need for accommodations, treatments or even research, because there’s nothing wrong with us. We can’t have it both ways.

            It’s hard to treat what you don’t understand. As you can see above, “ASD” folks have all sorts of different brain abnormalities. To say nothing of the fact that many of the people you seem set on including in the “ASD” spectrum are ~normal, albeit with mildly antisocial tendencies.

            >disease /dis·ease/ (dĭ-zēz´) any deviation from or interruption of the normal structure or function of any bodypart, organ, or system that is manifested by a characteristic set of symptoms and signs and whose etiology,pathology, and prognosis may be known or unknown.

            Define “normal.”

            http://jwilson.coe.uga.edu/EMAT6680Su09/Floer/6690/Stat%20Essay/normal_curve.gif

            ==========

            Unfortunately, that’s where the saved version ends, as far as I can see.

            So…

            >I can glean from your stance that you have a loved one that has been diagnosed, possibly recently…

            Nope, and I’m assuming that my original response to your conjecture is why you successfully managed to get my comment moderated. As I’m sure you read and can easily recall what was written here, I see no reason to reiterate it.

            : )

            I’ve read enough of your unjustified ramblings here. Keep your blog.

          • Savage

            You are providing nothing but speculation and insults. Your statements run counter to current studies and science… As I said…I am done with you. good bye.

          • AnOski

            >You are providing nothing but speculation and insults. Your statements run counter to current studies and science…

            …He said to a long, thought out reply that included three relevant papers published recently, with hundreds of citations apiece.

            You could put more effort into your lies.

          • Metalhead Nick

            Yeah anoski raises it, but since the underlying mechanisms aren’t understood, it seems hard to rule out convergent symptoms with divergent underlying causes. Or maybe they can, I’m not an expert. One of my buddies has worked with autistic kids for several years now. He does it in public schools for the ones that can go there and in home for more severe cases. He claims he can tell if someone has ASD and it’s severity by just looking at them. He also claims to be able to tell which parent passed it along even if they seem normal (sometimes both parents, he claims that their kids display the worst symptoms. My theory a while ago is that it is passed down maternally since ASD manifests itself much more infrequently in women so they seem normal enough but are still carriers…). I’m still curious and I’ll ask him too but how one rules out convergent symptoms if the underlying mechanisms are not understood.

          • AnOski

            Long story short – we don’t know yet. It’s going to take some serious genetics research and neuroscience to sort it out.

            But there’s almost no chance that it’s a simple recessive trait (shown with genetic / inheritance studies) and your friend is full of crap.

          • Metalhead Nick

            Well that was somewhat tongue in cheek. And yes my friend is full if crap. But ASD does tend to run in families (I know that is not always the case). He actually works with a couple with three autistic children and they were trying for a fourth child. I am not sure how he claimed to be able to tell these things but when we were discussing it as an example he brought up one of my ex-girlfriend’s sisters. He decided she was a potential “carrier” (she is a bit odd, but normal enough). Then he asks me about her kid. I hadn’t thought about any of them in a while, but I had to admit that the last I knew her son was almost two and still couldn’t talk…all that aside if autism does run in families, it has to have genetic underpinnings, obviously not simple genetic recession, but environmental, experiential factors would not explain this. It’s a combinatory effect. That is if ASD is all one actual thing. It would be easier to explain away that autism runs in some families, but is unique in it’s occurrence in others if it were not actually one disorder, but convergent symptoms with multiple causes. And that leads us back to the problem of having a psychological label for which no root cause is known.

          • AnOski

            “multifactorial inheritance.” I don’t use the term above, but definitely address it somewhere in this thread. Not simply inheritance, etc. But still inheritance.

            >That is if ASD is all one actual thing.

            It isn’t. The fact that it can be passed down but it’s not a simple recessive/dominant trait means that different genes trigger different phenotypes/effects. So different combinations will yield different disorders.

            E.g. Gene mutation A = increased ventricle volume, B = decreased grey matter thickness, C = higher neuron density, D = ….

            Add them all together in different combinations and you get a different thing, almost every time…

            It sounds like we may ~agree. I just shy away from calling them all the same disease when you have such obvious differences in brain morphology as described in the above paper.

          • AnOski

            Not so far off, though your analogy goes a bit funny with the birds. But, yeah. Spectrum. Except not a spectrum because we’re probably including several different endocrine and genetic disorders and calling it ASD, so we’re seeing a range of symptoms — in ranges of severities — and categorizing it as “ASD.” Overlapping spectrums, at least in terms of symptomology.

            So when a study like this comes along and says “they’re not all the same,” I just roll my eyes. Of course their brains aren’t the same. Why would you expect them to show identical differences? The only background information you had was that they had low IQ’s, and someone interpreted that and other symptoms as “ASD.”

            Psychology is a horribly crude and unscientific system, because of how it differs from neuroscience. Psychologists categorize and fix neurological disorders by looking at symptoms, not the brain. It’s like trying to understand why a computer’s broken by interpreting the corrupted documents it tries to print.

            This paper is a step in the right direction, but it’s embedded in the same backwards paradigm of ‘symptoms first.’

          • labastar

            The problem with you comment about genes is that there have been numerous studies with many thousands of individuals that scan for genetics differences between ASD cases and controls. Findings have been weak and difficult to replicate. Where are the robust associations between genes associated with thickened cortex and ASD? There is something strange about this autism phenotype, and you can see this from the genetic perspective as well.

          • AnOski

            >Findings have been weak and difficult to replicate. Where are the robust associations between genes associated with thickened cortex and ASD?

            This is typical of complex or multifactorial disorders, caused by multiple genes. And this makes perfect sense when you look at the wider context of “ASD” subjects exhibiting a wide range of symptoms.

            The disparity in results re. a single “simple” issue like a thickened cortex are also easy to explain. Hardly anyone ever has “just” a thickened cortex. Whenever anything like that happens in the brain, there are almost always other abnormalities (e.g. atypical protein distribution across cortex, etc.), which vary in nature.

            http://journals.lww.com/co-pediatrics/Abstract/2003/12000/The_ARX_story__epilepsy,_mental_retardation,.4.aspx

            >There is something strange about this autism phenotype, and you can see this from the genetic perspective as well.

            Even that’s not really a phenotype. It would be like saying birds with green feathers are exhibiting a “green feather phenotype.” Except, some look like this:

            http://upload.wikimedia.org/wikipedia/commons/0/07/Eclectus_roratus_(male)_-juvenile_pet_-8d.jpg

            And others look like this:

            http://wallpoper.com/images/00/38/63/64/green-birds_00386364.jpg

            Same effect, kind of. At least at a glance. But upon closer inspection, one is iridescent, while the other is simply green. What we see is pretty similar, but not really identical. Would you expect the same gene(s) to be responsible? Maybe…

          • labastar

            The thing is, most diseases are complex and involve many genes, and yet methods like GWAS have found associations between SNPs and these diseases. Why are we able to find genetic associations with diseases/traits like type 2 diabetes, age-related macular degeneration, Alzheimer’s, height, BMI, etc., etc., etc. but not autism? What I am saying is that autism is emphatically not typical in terms of difficulty in establishing genetic correlates. There is probably no phenotype for which so much energy has been expended in the field of genetics with so little knowledge gained.

            I definitely agree with you that what we call autism is actually probably a collection of phenotypes that are all lumped together because of clinical similarity. However, people who work in the intersection of psychology and genetics have recognized this problem (the lack of robust associations also seems to affect research on many psych diseases), but their attempts to break down the autism phenotype hasn’t been very successful either.

            The reason for my comment (as a person who seldom comments) is that people who are not working in the field of human genetics may have the impression that the genetics/autism riddle has been solved. The media is really great at trumping up results that later get chucked into the dustbin. I simply wanted to point out that even endophenotypes like cortex thickness (let alone autism) are not transparent on the human genetics level, by any means. I found it interesting that those in neuroscience are having a hard time cracking this nut as well.

          • AnOski

            >The thing is, most diseases are complex and involve many genes, and yet methods like GWAS have found associations between SNPs and these diseases. Why are we able to find genetic associations with diseases/traits like type 2 diabetes, age-related macular degeneration, Alzheimer’s, height, BMI, etc., etc., etc. but not autism?

            Easy. “Autism” isn’t one disease. It’s a suite of genetic abnormalities (we don’t know how many) that exhibit a wide range of symptoms. But, thanks to classical psychology’s habit of diagnosing via outwardly exhibited symptoms, we’ve lumped them all together as “ASD.”

            Despite the fact that “ASD” is known to manifest with a wide range of symptoms in a wide range of severities.

            >What I am saying is that autism is emphatically not typical in terms of difficulty in establishing genetic correlates.

            Well, “ASD” symptoms sure vary a lot more than any of the other diseases you mention, except for obesity/BMI, which is another case of similarly outward symptoms that can be caused by a variety of issues, ranging from genetic predispositions to habitual overeating to various types of cancer.

            >There is probably no phenotype for which so much energy has been expended in the field of genetics with so little knowledge gained.

            “ASD” is not a phenotype. “Autism” is not a phenotype. See my analogy re. green feathers above.

            >I definitely agree with you that what we call autism is actually probably a collection of phenotypes that are all lumped together because of clinical similarity. However, people who work in the intersection of psychology and genetics have recognized this problem

            They’re not really dealing with it if that’s the case (case in point: this study).

            >(the lack of robust associations also seems to affect research on many psych diseases), but their attempts to break down the autism phenotype hasn’t been very successful either.

            You’d need to get comprehensive genetic sequences from large pools of “ASD” patients and compare to outwardly exhibited symptoms. So far as I know, no such study has been conducted. The study above wasn’t looking for subgroups using this criteria: only overall correlation. It did note that other smaller studies had found greater correlation amongst perhaps more ‘selected’ subgroups of ASD patients, but that wasn’t the focus of this work.

            >The reason for my comment (as a person who seldom comments) is that people who are not working in the field of human genetics may have the impression that the genetics/autism riddle has been solved. The media is really great at trumping up results that later get chucked into the dustbin. I simply wanted to point out that even endophenotypes like cortex thickness (let alone autism) are not transparent on the human genetics level, by any means. I found it interesting that those in neuroscience are having a hard time cracking this nut as well.

            I generally agree, although I don’t know why you would get the impression that ASD is a solved riddle from anything written above.

          • labastar

            >”You’d need to get comprehensive genetic sequences from large pools of “ASD” patients and compare to outwardly exhibited symptoms. So far as I know, no such study has been conducted.”

            Of course this type of study has been done! There’s been an enormous amount of work on sub-types (e.g. autism with language delay), super-phenotypes (e.g. autism+bipolar+schizophrenia), and endophenotypes of autism. Respectfully, you are not the only one who has come up with the notion that autism is actually a cluster of diseases with diverse genetic etiology!

            >”They’re not really dealing with it if that’s the case (case in point: this study).”

            You seem to believe that since the genetic causes of autism have not been found, that researchers have not been doing it right. That’s the kind of stubborness that wastes a lot of time and research dollars. There are a lot of people that believe autism is strictly a genetic disorder (as the very large heretability estimates would indicate), and that if we simply sliced up the phenotype in such a way, or if we applied this particular modeling strategy, that the genetic picture would finally emerge. But it just isn’t working out that way. There are definitely cases of autism that are explained by rare mutations and/or cnvs. But the vast majority of cases remain unexplained on the genetic level. I believe it is time to shift the focus somewhat towards enviromental (and not just epigenetic) causes for autism. The genetic research has been pointing in this direction for years!

          • AnOski

            >>”You’d need to get comprehensive genetic sequences from large pools of “ASD” patients and compare to outwardly exhibited symptoms. So far as I know, no such study has been conducted.”

            >Of course this type of study has been done! There’s been an enormous amount of work on sub-types (e.g. autism with language delay), super-phenotypes (e.g. autism+bipolar+schizophrenia), and endophenotypes of autism.

            Mostly no. A few (very) recent studies like this one have actually taken the correct analytical approach:

            http://www.nature.com/nature/journal/v515/n7526/full/nature13908.html

            But the majority of previous work still looked at trying to classify or guess at different autism phenotypes as a filter when looking at genetic data. As far as I’ve seen in the literature.

            It’s going to take an unbiased big-data approach with respect to genes before anything meaningful is found.

            >Respectfully, you are not the only one who has come up with the notion that autism is actually a cluster of diseases with diverse genetic etiology!

            And you’re not the only one familiar with the relevant literature.

            >>”They’re not really dealing with it if that’s the case (case in point: this study).”

            >You seem to believe that since the genetic causes of autism have not been found, that researchers have not been doing it right. That’s the kind of stubborness that wastes a lot of time and research dollars.

            If by “wasting” you mean “allocating funds to work that might actually be able to determine the root causes of the disease(s),” then sure.

            >There are a lot of people that believe autism is strictly a genetic disorder (as the very large heretability estimates would indicate), and that if we simply sliced up the phenotype in such a way, or if we applied this particular modeling strategy, that the genetic picture would finally emerge.

            There are indeed some people who make that claim, but, as is generally accepted, genes typically denote a ‘predisposition;’ risk is also determined by epigenetic factors.

            >But it just isn’t working out that way. There are definitely cases of autism that are explained by rare mutations and/or cnvs. But the vast majority of cases remain unexplained on the genetic level.

            To which you apparently say “it’s not worth looking at the genes any more, even though we haven’t fully sequenced them in most cases and definitely don’t fully understand them yet.”

            >I believe it is time to shift the focus somewhat towards enviromental (and not just epigenetic) causes for autism.

            The study of epigenetics *is* the study of gene-environment interaction: gene expression as determined by environmental influence. This has been a branch of mainstream psychology for decades.

            Which isn’t to say this is a good approach. Good luck with understanding gene-environment interactions when you don’t even understand how the genes are relevant in the first place.

            >The genetic research has been pointing in this direction for years!

            You’re entitled to your opinion, but it is just that.

          • labastar

            Ever notice that some people are very rigid in their opinions and have difficulty changing their minds? I think the next GWAS I’m going to run will be on this trait. I’ll recruit cases among the frequent commenters of the internet. I’ll let you know what I find.

          • AnOski

            Just make sure to use the term “epigenetics” correctly in your write-up….

        • Savage

          No. It didn’t. Normal is iq100… it focused on individuals that were not labeled mentally deficient.

          And, the severity is rarely diagnosable based on observable physical criteria.

          A big part of the severity of an Autistic Spectrum Individual’s severity of condition is all built around the intervention, specialized training, normalization they receive when very young.

          This is coming from an Autistic Spectrum Adult who has spent his life researching my condition.

          • AnOski

            >No. It didn’t. Normal is iq100… it focused on individuals that were not labeled mentally deficient.

            Right, but they chose people with IQ’s lower than 70. Which apparently means they chose from the lowest ~2% of people at large vis a vis IQ test scores.

            I don’t know what label is “appropriate,” but, IMO, if you’re in the bottom 2% of anything, that’s pretty close to being “deficient.”

            >And, the severity is rarely diagnosable based on observable physical criteria.

            Based on the wording of the study, it sounded as though they were choosing based upon the ability of the subjects to follow directions, etc.

            So, the study subjects were “high functioning ASD patients.”

            >A big part of the severity of an Autistic Spectrum Individual’s severity of condition is all built around the intervention, specialized training, normalization they receive when very young.

            This is debatable. Many ASD children get abundant help from a young age, and it doesn’t help to make them any more self-sufficient, etc.
            >This is coming from an Autistic Spectrum Adult who has spent his life researching my condition.

            The fact that you can write as you do suggests that you are probably significantly “higher-functioning” than the subjects of this study.

            ….Which doesn’t say anything about the underlying genetic or other causes of the “ASD” disorder(s), etc. Particularly mild diagnoses seem to involve introverts who may or may not have similar genetic or other symptomatic similarities to other people with autism, etc.

      • Savage

        Except that a) the reduction in sample size “improved” accuracy – which is counter to scientific study and method, thereby showing a flaw in the experimental methodology. b) It rons counter to current studies showing that excess synapses in the brain are a hallmark of autism, which is a MAJOR difference that will not be reflected in the structural analysis and c) High Definition Fiber Tracking is showing a different path of nerve bundles in autistic brains…

        The paper, I fear, is wrong.

        • Metalhead Nick

          I thought the “improved” results was meant to show that small sample sizes give more false positives…I didn’t go back and reread. But I agree I thought that they had discovered that autistic brains were more connected than normal. And that would not be shown at a gross anatomical level.

          • Savage

            I cannot get a full copy of the study as it is not in my pay services… so I can’t speak to the specifics of it…

            but do a search for high definition fiber tracking and temple grandin on google images.

          • http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

            That’s correct, Metalhead Nick. The fact that smaller sample sizes had higher positive rates, almost certainly indiciates that those were false positives, and reflects a methodological weakness (of the multivariate classifier).

    • http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

      Actually, the authors of the paper themselves played down the positive results. I’ve quoted some of what they said in the discussion. In the Abstract they say:

      Comprehensive univariate analyses using volumetric, thickness, and surface area measures of over 180 anatomically defined brain areas, revealed significantly larger ventricular volumes, smaller corpus callosum volume (central segment only), and several cortical areas with increased thickness in the ASD group.

      Previously reported anatomical abnormalities in ASD including larger intracranial volumes, smaller cerebellar volumes, and larger amygdala volumes were not substantiated by the current study.

      In addition, multivariate classification analyses yielded modest decoding accuracies of individuals’ group identity (<60%), suggesting that the examined anatomical measures are of limited diagnostic utility for ASD.

      While anatomical abnormalities may be present in distinct subgroups of ASD individuals, the current findings show that many previously reported anatomical measures are likely to be of low clinical and scientific significance for understanding ASD neuropathology as a whole in individuals 6–35 years old

      • AnOski

        >Actually, the authors of the paper themselves played down the positive results.

        Yes and no. See below.

        >Previously reported anatomical abnormalities in ASD including larger intracranial volumes, smaller cerebellar volumes, and larger amygdala volumes were not substantiated by the current study.

        Right, but this study also focused on “high-functioning individuals with IQ >70).” In other words, they’re selecting for normalcy. Your statement appears to apply this conclusion to all people across the S of ASD, so to speak. That probably isn’t a good idea, IMO.

        >In addition, multivariate classification analyses yielded modest decoding accuracies of individuals’ group identity (While anatomical abnormalities may be present in distinct subgroups of ASD individuals, the current findings show that many previously reported anatomical measures are likely to be of low clinical and scientific significance for understanding ASD neuropathology as a whole in individuals 6–35 years old

        When taken as a single data set. Which, again, is not surprising. And since we’re looking at high-functioning individuals, the lack of large observable differences is, again, not at all surprising. Half of the ‘normal’ population is ‘below average,’ after all. Many people not diagnosed with ASD have IQ’s lower than 70.

        • zorro4

          Not many actually. Over 97% of people in this world have an IQ greater than 70 so I’d say this is a pretty representative sample

          http://blogs.njit.edu/ajz4/files/2009/10/iq_bell_curve1.gif

          • AnOski

            You still wouldn’t expect those 2-3% to have drastically abnormal brains, and ASD isn’t just “an IQ lower than 75.” You’re assuming far too much.

        • shayneo

          This seems perfectly valid. Its not proven that Autistic individuals with impaired intelligence are impaired BECAUSE of the autism. The comorbid factos might well just be because of something else, possibly unrelated, or an injury, or whatever. This approach takes it that they won’t examine those cases and just go for cases where the only discernable ‘fault’ is the autism, which significantly cleans up the dataset.

          • AnOski

            >Its not proven that Autistic individuals with impaired intelligence are impaired BECAUSE of the autism.

            Right, but then how are you going to figure this out by looking at a bunch of people with a set level of impairment (in this case, an IQ of ~70), who may or may not have autism.

            >The comorbid factos might well just be because of something else, possibly unrelated, or an injury, or whatever.

            Well, this wasn’t a study on people with brain injuries, but, otherwise, yes. It could easily be unrelated disorders.

            >This approach takes it that they won’t examine those cases and just go for cases where the only discernable ‘fault’ is the autism, which significantly cleans up the dataset.

            Except, this isn’t how you diagnose autism. You don’t diagnose autism by looking at brain morphology. Because of things like comorbidity; you might as well diagnose someone who’s abnormally tall with a disorder just by looking at them. The actual problem could be due to a tumor in their brain, endocrine disorder, etc., but you’re just looking at the symptoms and saying “this is it!” We need a neuroscientist in the room…

  • Kyle Paskewitz

    This is a very interesting article. However, I have to question the conclusion that “This suggests that anatomical measures alone are likely to be of low scientific and clinical significance for identifying children, adolescents, and adults with ASD or for elucidating their neuropathology.” While I agree that anatomical measures alone do not paint a complete picture, I disagree that they are of low scientific or clinical significance. This study does not address the theory that anatomical structures combined with environmental or other external factors could be the cause of autistic behaviors and whether a person with a specific brain anatomy is more or less likely to display signs of autism, or whether they become high or low functioning individuals when exposed to those external factors.

    • theLaplaceDemon

      In this context, the root cause of autism is not what is being studied. It looks for brain differences, on a specific level (that of gross anatomy).

      We know that there is probably *something* different about the brains of people with autism, given that autism is diagnosed by behavioral differences. What we don’t know is where those differences lie: Is it microstructure? Is connectivity different? Are neuromodulatory factors different? Is is something about cellular physiology? The external/environmental factors you mention could be a causal factor in whatever those differences are, but we none the less should be able to (at some level of analysis) see differences regardless of what the causal factor is. So saying “it’s brain structure and environment!” is meaningless in this context because any environmental influence should still lead to a neural difference of some sort for us to measure. What caused that neural difference is a separate question.

      • http://www.facebook.com/felonious.grammar Felonious Grammar

        Hmm. It seems to me that there aren’t enough measures in this study to rule out brain functioning abnormalities. I have MS, for instance, there are identifiable lesions on my brain; but unless I get one on my optic nerve, there is pretty much no telling what lesion causes what problems. What MRIs can tell us is pretty limited.

        I kind of doubt that a developmental disability would show up on an MRI, much of our wiring, thinking processes, and sensory processing are still quite obscure, I think, and blood flow can only tell us so much.

        I could be wrong and am not a scientist, but am fascinated with the brain/mind. I also agree with petross that part of the problem with reliability in such studies is likely the unreliability and subjectivity of the taxonomy in the DSMs and a tendency to over-diagnose and to misdiagnose in the field of psychiatry, along with a general neglect of environmental effects in human functioning in biological psychiatry.

        • theLaplaceDemon

          “t seems to me that there aren’t enough measures in this study to rule out brain functioning abnormalities.”

          Remember, this study is only measuring one very specific thing – gross anatomy. It doesn’t rule out brain functioning abonormalities (which would be cellular response properties) because it is not asking that question. It is asking one very simple thing: When we look at this massive data set, are there are differences in the gross anatomy between these two populations? And the answer, according to this data set and method of analysis, is no.

          You say: “I kind of doubt that a developmental disability would show up on an MRI,
          much of our wiring, thinking processes, and sensory processing are
          still quite obscure, I think, and blood flow can only tell us so much.”

          First, this is MRI, not fMRI, so blood flow is not what is being measured here.

          However, to your point about it being unlikely that MRI would show the relevant differences in autism – the reason this study is such a big deal is because many others *have* claimed to find differences. As noted in the original post, these are usually small studies, and they don’t all agree with each other, which is fishy. This study is a big deal because, using a large dataset, it gives us some fairly good evidence that all those small studies may have been false positives.

          The scope of this study is fairly limited, but it’s importance comes from the fact that it refutes many others.

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  • Kyle Jasmin

    I wonder if data quality may be an issue here, specifically head movement artifacts, which are detrimental to high-resolution anatomical scans as well as EPIs. Five of the contributing sites at least *mention* movement in their quality control statements:

    Kennedy Kriger, NYU & Oregon: “As datasets with a wide range of
    image quality are being shared, only the most extreme cases of movement were excluded from this sample.”

    Caltech: “We shared data from every participant that we had at least 1 scan from (i.e., we did not exclude participants entirely from this dataset on the basis of movement).”

    Stanford: “We submitted data that has been quality controlled for various artifacts including movement.”

    The other sites don’t seem to have considered quality or movement, at all. They say either “We submitted all collected data, regardless of movement/quality”, or provide no information about anatomical scan quality.

    The large sample size is admirable, but this study may have forsaken quality for quantity.

    Scan parameters and quality control statements are published here:
    http://fcon_1000.projects.nitrc.org/indi/abide/

  • Jon Brock

    The study is showing that there are few if any differences in the mean values for each group. But if we actually take heterogeneity seriously then we should be looking at the individual variability rather than group averages.

    Just eyeballing the figure, it would seem that there are more extreme values in the autism groups. It would be easy to look at the number of people with autism who are outside say the 95% confidence intervals for the controls. It would also be interesting to see if the standard deviations across studies are larger for the autism groups than the controls.

    • http://geekfriendly.org Dan Lurie

      I get the same sense as Jon; the heterogeneity found across subjects in the ASD group is likely making it difficult to find any consistent differences. This isn’t so much an issue with the study, but just a fact of life when trying to identify brain biomarkers for psychiatric illness. Diagnoses are categorical, the brain and behavior aren’t.

    • http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

      I agree, I actually was a bit disappointed that Haar et al. didn’t test for differences in variance across groups.

      Maybe they did and that’s going to be another paper 😉

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  • http://petrossa.me/ petrossa

    Very simple answer, always the best. The ‘pool’ of autism diagnosed persons is so heavily polluted with ‘whatever they have’ persons (caused by the vague definition and therefore useless tests for diagnosing it) that no useful information can be gleaned from it.
    Studying an ill defined problem is pretty pointless

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  • Eric377

    What percent of ASD individuals are considered high functioning? Why would this study not use the whole spectrum? Was it an inability of such people to properly have MRIs conducted?

    • theLaplaceDemon

      I don’t know this for certain, but probably, yes. High-resolution MRI requires you to stay very, very still. From what I gather small head movements are a big problem when doing research with lower-functioning autistic people.

  • Tad Blair Lab

    “It’s important to remember, however, that this paper only considered
    brain anatomy. It doesn’t contradict studies looking at brain function,
    nor does it relate to microanatomy or neuropathology (i.e. microscope work.).”

    Do research studies that look at brain function, microanatomy, and neuropathology use larger sample sizes? Are they conducted by researchers whose incentives are less warped by constant pressure to produce positive findings so they can renew their research funding?

    I wonder what percentage of the entire Pubmed database now belongs in our junk mailboxes.

    • http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

      Well studies on brain function are getting pretty big now, and data sharing of fMRI studies means that sample sizes can reach the 100s (just like in this structural study.)

      However microanatomy and neuropathology studies tend to be tiny. Single-figure sample sizes are common (per group).

  • http://www.oxyhealth.com/ Chloe Paltrow

    Though the author have stated that there is an increased ventrical size for the ASD people found in that survey, does not mean that all increased ventrical size is the reason or symtoms of ASD.

    I agree with the author that there is no difference of brain anatomy between the normal and ASD affected people (the survey is actually saying that).

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  • Eric377

    Is there a therapeutic rationale for this study or the other studies? It can be a not currently existing hypothetical therapy. The summary language makes it sound as if the whole thing was entirely diagnostic. I have an autistic son and I am 98% certain that MRI-based diagnosis methodologies should not be a high priority, unless some doctor is going to take that MRI and do something useful for the patient. No one will base an ASD diagnosis on these measurements even if they had some more significant variances absent observed behaviors. Should I be glad that scientists are studying the problem or should I be angry that resources that might have gone to therapy were spent on MRIs and analyses of the results?

    • http://scienceoveracuppa.com/ Emily Casanova, PhD

      Currently, some researchers are working on using MRI as an early means of diagnosis, which is extremely important in starting the treatment process as soon as possible. Not that that has a lot to do with the above study, but MRI in general will hopefully prove diagnostically useful. Right now, an excessive amount of time goes into diagnosis; ideally, MRI could cut down on that time, allowing behavioral therapy etc. to begin even earlier. In general, earlier intervention correlates with better outcomes later on, so that’s definitely a priority.

      Also, too, I’d caution not to baulk at the usefulness of basic science. While its benefits might not be directly apparent, it’s definitely the foundation to all clinical science I promise you. Even if many studies only help us to understand what autism IS, that process is still necessary in helping produce the kinds of clinical studies you as a parent would be more interested in. We need to know what it is in order to better treat it. Otherwise we’re just groping in the dark and wasting far more resources in the meantime.

      (By the way, that isn’t to say that science is perfect. Like any complex system, there is waste of resources, as well as a poverty of resources going where they could be better used. But there is currently a growing branch of science that studies science itself in order to make it more efficient, so hopefully that waste will reduce with time and better means of allocation.)

  • EllieM

    There’s a problem with the image of the scans at the top of this article. These scans are 2 copies of the exact same scan. They are not two different people. First of all, different people will have slightly different brain scans even if they are both normal. However, the bony portions of these two images are identical. You won’t get that in two different people. Everyone’s bones are unique and you wouldn’t even get this precise of a match in two scans of the same person (patients move, technicians are unlikely to start scanning at precisely the same spot as a previous scan, etc.)
    I doubt the image has anything to do with the actual study and was just added to emphasize the similarities between patients, but unless you are going to use actual images from the study – from DIFFERENT people, don’t bother adding an image to the post at all. It comes off as disingenuous.

    • http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

      Yes the image is a light-hearted one, as are most of my images except the ones taken from papers, and I hope it’s obvious from the context which are which.

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  • CSB

    It seems like the paper is reporting a solid finding, but it seems like a poor choice to restrict their comparison to “high functioning” ASD vs. control. After all, there are no hard tests to diagnoses ASD, and many individuals who receive a diagnosis of high function ASD (such as Aspergers) from one clinical will be diagnosed with some other cognitive disorder (or found to be “neurotypical”) by another clinician, It seems plausible that individuals affected with more profound forms of ASD would be more likely to exhibit irregularities in neuroanatomy. Also (as pointed out here) some of the more recent papers in this area have focused on disorganization of the cellular layers in key brain areas (see Stoner et al, New England J. Med. 2014, for example), which would not be detected by a standard MRI anyway, so overall, while this seems to be a meaningful finding, I think the assessment here of the paper’s impact is a bit hyperbolic…

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  • Toni Donahue

    What about low functioning/profound Autism comparisons to the typical brain?

  • http://www.locomotivebreath1901.blogspot.com/ locomotivebreath1901

    As father to an adult son with ‘high-functioning autism spectrum disorder (ASD) (it’ll always be Aspergers Syndrome, to me),’ I find this article to be mildly interesting, yet of limited therapeutic value.

    It is simply another piece to a very unpredictable puzzle that is the eccentric world of ASP people – a world that is theirs; others simply live in it.

  • stmccrea

    Important scientific principle: it is assumed that the hypothesis (people with autism have brain differences) is false unless there is evidence to prove the contrary. Then it is only held true if vigorous efforts to disprove it or provide a better explanation fail over repeated experiments. The authors are absolutely correct to dismiss small findings that aren’t consistent across the group as not constituting proof of the initial hypothesis, because these findings would not be large or consistent enough to convincingly support the original hypothesis.

    One person below made a good point: there may be subgroups within the larger group that have a particular set of brain differences, and it’s legitimate to study these groups. But that would mean the hypothesis is still not supported for “Autism,” as it would not apply to the diagnosis group as a whole. Of course, if it did turn out to be true that different subgroups had different physiological differences, while the majority had no such differences at all, a true scientist would acknowledge that this means the Autism diagnosis itself is called into question as a legitimate grouping or disorder.

    Psychiatric disorders as a whole are concocted by consensus of a group of clinicians, rather than on any biological marker or test. And clinicians, being human, are subject to biases and social conditioning that makes them unreliable at distinguishing genuine disease states from social constructs that make them feel like they “understand” something that they don’t. The scientific method was devised just to overcome such biases, and it starts with a very skeptical set of assumptions requiring a high level of proof before believing any hypothetical explanation of anything. We would do very well to respect genuine science as these folks are providing to us, and to continue to be skeptical about the presence of significant brain differences until we see proof they exist, rather than assuming they are present and objecting when the evidence casts doubt on our preferred beliefs and assumptions.

    —- Steve

  • Pingback: Most Autistic People Have Normal Brain Anatomy – Neuroskeptic | DiscoverMagazine.com | TRANS RESEARCH()

  • http://dev.blogs.discovermagazine.com George Davis

    This may raise questions in other areas of neuroscience that use small samples to study brain anatomy.

  • http://scienceoveracuppa.com/ Emily Casanova, PhD

    This is not shocking, particularly when using high-functioning individuals. I’m assuming the reasoning is because HF are more capable of following instructions and sitting inside a scanner for 45 minutes+. The MIND Institute has been working on a longitudinal MRI study following ALL ranges of functioning, having developed a protocol to work carefully in training LF and MF kids as well. A significant minority have megalencephaly; meanwhile, a significant minority also have microcephaly. Previous work has typically found that those with microcephaly have other associated medical conditions and may more often than not have a genetic disorder.

    In terms of neuropathology, i.e., the microscope work that the author of the above media article decided to only briefly mention on his/her way to a jaw-dropping headline, there have been a number of studies that have found distinctive neocortical malformations in ~92% of all samples studied. These include dysplasias, heterotopias, etc. Increased gyral complexity is also an extremely strong predictor of autism.

    So, yeah, not keen on the spin of this article. Bad on you, Discover. Even though I’m sure the authors of the piece themselves played up the “importance” of their findings, frankly as an autism researcher, the findings AS THEY ARE are interesting enough. Because what does it tell me? It says to me that, on average, those with either megalencephaly or microcephaly are going to fall into the more severely affected ranges of the spectrum and that the place to investigate HF individuals is at the microarchitectural level.

  • quant

    I suspect that the reason they were unable to classify ASD and controls using machine learning techniques is because ASD is highly heterogeneous in it’s symptomatology and biological underpinnings. Hence there are likely subgroups, which can only be identified using data-driven clustering where groups are not identified a priori.

  • Pingback: Autism, brain anatomy, brain function, and coming to careful conclusions | Khendra's Nerdy Neuroscience Blog()

  • ddsouza

    Sounds like a nice paper. Was any attempt made to match the participants on Chronological Age (CA)? I realise that brain structure changes very little during adulthood, but it does change, and some of these participants are as young as 6 years of age. It would be interesting to show no (or little) differences irrespective of CA.

  • JR King

    Thank you for pointing this article.

    I am troubled by the fact that subsampling increases decoding score. I have tried to simulate this effect, in vain.

    https://gist.github.com/kingjr/ef64b63dbbde06455a2d

    I initially thought that this effect may be due to a heterogeneity of the ASD group, implying that only a non-linear classifier could capture the effect, but this hypothesis does not seem to hold. Anyone manages to simulate this effect?

    Thanks!

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  • Pingback: Autistic Traits Aren't Linked To Brain Anatomy? - Neuroskeptic()

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Neuroskeptic is a British neuroscientist who takes a skeptical look at his own field, and beyond. His blog offers a look at the latest developments in neuroscience, psychiatry and psychology through a critical lens.

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