Interesting neuroimaging study regarding Optimal Outcome (indistinguishable from peers, “recovered”)

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Winnie
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Interesting neuroimaging study regarding Optimal Outcome (indistinguishable from peers, “recovered”)

Postby Winnie » Thu Mar 17, 2016 4:28 pm

Interesting neuroimaging study regarding Optimal Outcome (indistinguishable from peers, “recovered”) -- speaks to the question of whether the neural function of children with autism who become indistinguishable (OO) becomes neuro-typical (NT) or if it is more similar to ASD (atypical) with unique neural compensation.

Neuroimage Clin. 2016; 10: 182–191.
Published online 2015 Dec 2. doi: 10.1016/j.nicl.2015.11.014

Language comprehension and brain function in individuals with an optimal outcome from autism

Inge-Marie Eigsti,⁎ Michael C. Stevens, Robert T. Schultz, Marianne Barton, Elizabeth Kelley, Letitia Naigles, Alyssa Orinstein, Eva Troyb, and Deborah A. Fein

Abstract
Although Autism Spectrum Disorder (ASD) is generally a lifelong disability, a minority of individuals with ASD overcome their symptoms to such a degree that they are generally indistinguishable from their typically-developing peers. That is, they have achieved an Optimal Outcome (OO). The question addressed by the current study is whether this normalized behavior reflects normalized brain functioning, or alternatively, the action of compensatory systems. Either possibility is plausible, as most participants with OO received years of intensive therapy that could alter brain networks to align with typical function or work around ASD-related neural dysfunction. Individuals ages 8 to 21 years with high-functioning ASD (n = 23), OO (n = 16), or typical development (TD; n = 20) completed a functional MRI scan while performing a sentence comprehension task. Results indicated similar activations in frontal and temporal regions (left middle frontal, left supramarginal, and right superior temporal gyri) and posterior cingulate in OO and ASD groups, where both differed from the TD group. Furthermore, the OO group showed heightened “compensatory” activation in numerous left- and right-lateralized regions (left precentral/postcentral gyri, right precentral gyrus, left inferior parietal lobule, right supramarginal gyrus, left superior temporal/parahippocampal gyrus, left middle occipital gyrus) and cerebellum, relative to both ASD and TD groups. Behaviorally normalized language abilities in OO individuals appear to utilize atypical brain networks, with increased recruitment of language-specific as well as right homologue and other systems. Early intensive learning and experience may normalize behavioral language performance in OO, but some brain regions involved in language processing may continue to display characteristics that are more similar to ASD than typical development, while others show characteristics not like ASD or typical development.

Continues -- full text of study: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707189/
Winnie
"Make it a powerful memory, the happiest you can remember."

Santosg
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Re: Interesting neuroimaging study regarding Optimal Outcome (indistinguishable from peers, “recovered”)

Postby Santosg » Fri Mar 18, 2016 3:14 am

Thanks for sharing the study.

I think that the study points to something very interesting and particular to the subset of autistic children that are 'recovered.' Obviously, autism is multifactorial. There are many causes. Some children will enter into intensive behavioral intervention and recover and some will remain severely autistic. Genetics plays a role in this but is certainly is not a simple question of genetics.

I think two critical takeaways are highlighted by the study.

1) That even with intensive intervention and functional recovery, these individuals did not create a neurologically 'typical' neural network. In fact, this actually shows that despite successful intensive behavioral and social adaptation, there was not a recovery of the normal brain regions and networks that are rooted in the emergence of autism.

2) These individuals had otherwise healthy brains. That is, given the right amount of stimulus, their brains were able to learn and adapt to their environment in a responsive way.

The question, therefore, becomes why they were not able to do this with certain brain regions. The answer, I think, is fairly obvious. There was something about those cells that make them unable to function normally. They were unhealthy, unresponsive. But not all cells--thank goodness.


I think that a significant subset of children that have autism are the results of brain injuries--produced in utero or shortly after birth. I don't think that you could really look at these results and discount that as a reasonable assumption.

The brain is extremely vulnerable in utero. Alterations to its development have devastating consequences, in a way that are not as impactful later in life. Because brain systems are widely distributed, the impact of a single cell or cluster of cell deaths is mitigated. So, with the little we know, it is assumed that we actually distribute a memory into thousands of little fragments across thousands of brain cells. They are retrieve and brought together in recall. Since a link has been established between these networks, even injury at a later date can be lessened. If the network as such has not been established, however, there is little that the cells can do to aid and help each other. They are inherently 'cut' of and never truly learn to communicate.

We see this with disease, also. Children that have hemispherectomies recovery so well precisely because the injured cells have essentially 'taught' other cells to do their job. By the time the procedure is performed, these jobs have been successful transfered to other brain regions with minimal impact on how the individual moves, speaks, or behaves. But why is this not the case with autism. Well, I think it is precisely because with some autistic children the damage happens at a very early stage. Before the brain has been able to function as a unity--however infantile it might seem.

Now, I use the 'social metaphor' of 'talking and learn' among brain cells deliberately. Very intentionally. And I think, very appropriately. When we see 'autism' as the macroscale, it is actually simple the final manifestation of behaviors that are taking place at the brain-regional-network-cellular level. Our cells exist within a cooperative community. They speak with each other, deliberate, and argue. But above all, cooperate. If there is a breakdown in communication--anything that hinders communication--problems emerge. These might manifest as 'chemical imbalances' or 'learning problems', but when they can't be inherently 'controls' it means something fundamental has broken down in how brain cells coordinate their behavior. Autistic brain cells don't communicate frequently, they are less 'social.' As a result, the broader organism is less able to work on complex tasks such as social interactions.

Winnie
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Re: Interesting neuroimaging study regarding Optimal Outcome (indistinguishable from peers, “recovered”)

Postby Winnie » Sat Mar 19, 2016 1:00 am

Santosg wrote:I think that the study points to something very interesting and particular to the subset of autistic children that are 'recovered.' Obviously, autism is multifactorial. There are many causes. Some children will enter into intensive behavioral intervention and recover and some will remain severely autistic. Genetics plays a role in this but is certainly is not a simple question of genetics.
I agree – we really don’t know the reasons children follow a particular trajectory. We can identify factors and interventions that correlate with children who achieved an OO outcome (see study below – contrasted with HF outcome),though there is still so much we do not know regarding why children follow certain trajectories:

J Dev Behav Pediatr. 2014 May; 35(4): 247–256.
Intervention History of Children and Adolescents with High-Functioning Autism and Optimal Outcomes
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487510/

Several years ago (well, 2012) a study was published that identified six developmental trajectories among a large study population of children diagnosed with autism. Perhaps the most striking (and unexpected) finding was identification of a trajectory -- “bloomers” -- whose diagnostic baseline was severe autism, but whose trajectory was rapid and remarkable:

Six Developmental Trajectories Characterize Children With Autism
http://pediatrics.aappublications.org/content/pediatrics/early/2012/03/28/peds.2011-1601.full.pdf

But since ^this study used info from the CA DDS database, other info on these individuals is limited.

Santosg wrote:I think two critical takeaways are highlighted by the study.

1) That even with intensive intervention and functional recovery, these individuals did not create a neurologically 'typical' neural network. In fact, this actually shows that despite successful intensive behavioral and social adaptation, there was not a recovery of the normal brain regions and networks that are rooted in the emergence of autism.
Yes – that is how I understand it – that generally the OO group functions and presents as neurotypical, but the underlying neural process is not like that of a subject considered typically-developing, on this specific language task anyway.

Santosg wrote:2) These individuals had otherwise healthy brains. That is, given the right amount of stimulus, their brains were able to learn and adapt to their environment in a responsive way.
We don’t really know if the subjects' brains in this study are otherwise healthy – I’m not really sure how that would be defined or determined.

Santosg wrote:The question, therefore, becomes why they were not able to do this with certain brain regions. The answer, I think, is fairly obvious. There was something about those cells that make them unable to function normally. They were unhealthy, unresponsive. But not all cells--thank goodness.
What about this though – would you similarly consider a child with dyslexia to also have cells (or brain regions) that are unhealthy/unresponsive/not functioning normally? Some functional imaging studies have shown that “recovered” dyslexic brains change to resemble typical readers (“normalize” -- mentioned in the paper). There was a researcher years ago (Shaywitz) who showed this change via pre/post fMRI following a specific and intensive reading intervention, but I haven’t kept up or looked up research in this area in a long time.

Santosg wrote:I think that a significant subset of children that have autism are the results of brain injuries--produced in utero or shortly after birth. I don't think that you could really look at these results and discount that as a reasonable assumption.
It’s certainly possible that a subset of autism is the result of something that happens in utero .

Santosg wrote:The brain is extremely vulnerable in utero. Alterations to its development have devastating consequences, in a way that are not as impactful later in life.[…] Since a link has been established between these networks, even injury at a later date can be lessened. If the network as such has not been established, however, there is little that the cells can do to aid and help each other. They are inherently 'cut' of and never truly learn to communicate.
Thinking about this – if that is so, then wouldn’t that mean that children whose parents report long over a year of typical, perfectly normal development, and then a sudden regression, would be more likely to “recover,” or even more rapidly compensate following an acute/acquired neurological insult of some type? Since their brains would presumably have a prior history of normal cell communication and regional connectivity? Because I don’t think that a marked, later regression is a developmental pattern associated with OO.

Santosg wrote:We see this with disease, also. Children that have hemispherectomies recovery so well precisely because the injured cells have essentially 'taught' other cells to do their job. By the time the procedure is performed, these jobs have been successful transfered to other brain regions with minimal impact on how the individual moves, speaks, or behaves. But why is this not the case with autism.
I find hemispherectomy accounts interesting too – incredible actually. I don’t really agree that the impact of surgical removal of a hemisphere has a minimal impact of how the patient moves and speaks though, especially since some skills may take a long period of intensive therapy to recover – including speaking, even more so reading, and especially movement of the side opposite the hemisphere removed. I think of recovery in these cases more as the brain compensating or relearning (plasticity) rather than skills/neurological jobs having been transferred pre-surgery.

So I guess I’m not really surprised that studies like this one indicate neurological compensation rather than normalization of neural processes – it seems to me that the goal of intervention is the teaching of skills in whatever unique way or compensatory manner (neural regions of strength?) a child is able to learn them. Learning physically changes the brain and creates new pathways and connections, even if the changes are not those one might observe in a typically-learning brain.

Santosg wrote:Well, I think it is precisely because with some autistic children the damage happens at a very early stage. Before the brain has been able to function as a unity--however infantile it might seem.
It will be interesting to see what comes of some of the prospective studies over time involving high risk (of autism) infants (those with a sib with autism). As far as neuroimaging – I’ve noticed several neuroimaging papers on infants – like this one presented during the International Meeting for Autism Research (IMFAR) in 2014 :

Language-related functional neuroimaging biomarkers in autism infants and toddlers with differing language outcome and developmental trajectory
https://imfar.confex.com/imfar/2014/webprogram/Paper16016.html

Since it may be a year or two (or more) from the time a paper presented at IMFAR is published in a journal (the study we are discussing in this thread was presented at the 2013 IMFAR but published only recently), there are probably many neuroimaging studies completed (and presented) since that time that have yet to be published (I checked the 2015 and 2014 IMFAR meeting archives -- there are many neuroimaging paper abstracts -- but I haven't read many of them) .

Of possible interest regardless of topic: The papers presented each year at IMFAR can be searched by year on the site archives – just go here, scroll down to "Links to Archives," click the link for the selected IMFAR year, and then scroll down to the search field. You can search any topic, like fMRI or neuroimaging (for purposes of this thread). The results will be displayed beneath the search box. These are abstracts, but often have more info than the (eventual) final abstract version accessible on pubmed.

You can also download the abstract book, but when I tried this several years ago, it was over 800 pages. So I wouldn’t recommend it – using the search is definitely less overwhelming!

All interesting to discuss but I certainly don't have all the answers here -- I’m still stuck in the zone of "the more I learn, the less I know." :)
Winnie
"Make it a powerful memory, the happiest you can remember."

Santosg
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Re: Interesting neuroimaging study regarding Optimal Outcome (indistinguishable from peers, “recovered”)

Postby Santosg » Sun Mar 20, 2016 6:49 am

Winnie wrote:What about this though – would you similarly consider a child with dyslexia to also have cells (or brain regions) that are unhealthy/unresponsive/not functioning normally? Some functional imaging studies have shown that “recovered” dyslexic brains change to resemble typical readers (“normalize” -- mentioned in the paper). There was a researcher years ago (Shaywitz) who showed this change via pre/post fMRI following a specific and intensive reading intervention, but I haven’t kept up or looked up research in this area in a long time.


This is a good point. The distinction I’m trying to make rests on the basic paradox that the study—and a number of others—have found with OO children. They demonstrate great neural plasticity, are able to achieve ‘neurotypical’ levels of function, understanding, and social interaction. So, they don’t have autism. The study demonstrates, however, that the areas of their brains that are associated with autism have not been rehabilitated. Instead, additional and distinct supportive networks are formed to help them navigate language and social interactions.

I am defining health simply in terms of responsiveness. As you mentioned, children with dyslexia simply need additional input to help them read normally. That is, the underlying area of the brain responsible for reading is capable of actually performing the required tasks. Yes, it requires additional amounts of time to get it up to ‘speed’ but it is responsive and mirrors the brains of normal readers.

This highlights the difference I’m trying to make between—using your example—the brains of dyslexic children—and children with autism. Some of these autistic children have truly damaged areas of the brain in local areas but not in the brain as a whole.

The biggest ‘question’ that is raised by these studies is why those areas of the brain prove unresponsive. I think it is reasonable to conclude that they are unable to response because they are damaged.

I don’t know if one can easily explain regressive autism. Certainly, there are genetic features associated with regressive autism. If the autism were the result of injury, however, I agree that their future recovery would be far more rapid. If it were associated with a clear injury, however, it would never be classified as autism to begin with. If the injury occurred in utero, on the other hand, there would be no basis to identify its origin. If it were localized into areas of speech the deficit would not be clearly identified until the child grew older.

We know that intensive intervention works. But only with some. Theoretically, I think there are some interesting parallels to be made to findings in exercise physiology. The ability of an individual to response to exercise varies incredibly.
http://www.ncbi.nlm.nih.gov/pubmed/21030666

Some people respond very well and others hardly at all. Some people can easily gain muscle and some cannot. I think there is probably something like this also going on in the case of OO. The relationship between exercise and brain health has long been confirmed. I think that this responsiveness is probably the underlying mechanism that has helped the OO children, that they run along the same genetic and molecular pathways.

Winnie
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Re: Interesting neuroimaging study regarding Optimal Outcome (indistinguishable from peers, “recovered”)

Postby Winnie » Mon Mar 21, 2016 10:46 pm

Santosg wrote:This is a good point. The distinction I’m trying to make rests on the basic paradox that the study—and a number of others—have found with OO children. They demonstrate great neural plasticity, are able to achieve ‘neurotypical’ levels of function, understanding, and social interaction. So, they don’t have autism. The study demonstrates, however, that the areas of their brains that are associated with autism have not been rehabilitated. Instead, additional and distinct supportive networks are formed to help them navigate language and social interactions.

I think you are saying that this is compensation, not cure (like curing or “reversing” damage so that the brain functions like that of a typical person). I would agree – but aren’t we always teaching the brain to compensate when we are teaching a child with autism a skill? I guess I’ve never really thought of it as reversing anything (like a damaged function -- cure) – I always thought of it as adding something (like a learned skill -- compensation). I actually don’t know of anything that has been shown to reverse brain damage (even if identified) in children with autism.

Santosg wrote:This highlights the difference I’m trying to make between—using your example—the brains of dyslexic children—and children with autism. Some of these autistic children have truly damaged areas of the brain in local areas but not in the brain as a whole.

But what about the severely-affected, non-verbal children who have intelligence in the normal range? I personally know a teen-aged child of a friend who has severe autism, is non-verbal, and yet with testing by a PhD who has expertise in this area and appropriate testing protocols, was shown a year ago to have average intelligence (I was present at the feedback appointment). So if the brain as a whole is damaged in children who don’t “recover,” how can intelligence still be intact?

I certainly don’t have all the answers, but related to that point (what is different about the brains of recovered children) – in the research surrounding OO, “recovery,” or similar, IQ (especially verbal IQ) is a variable associated with children early-on whose outcome is later indistinguishable. I have to say that this gives me pause for a number of reasons – especially since testing IQ in children who have a significant language disorder can be an iffy business in the hands of many professionals. And also probably because my son fell into (terminology of study to follow) the “cognitively less able” (VIQ <70) when tested at 3 ½, though not so as he progressed (and later, the opposite actually). So I worry about scores on even younger children being misused to make predictions regarding potential.

That said, here is the study – it is unique in that it is a prospective study following children from age 2 to age 19. Since I couldn’t locate a copy of the full text that wasn’t behind a pay wall, I included some links following the abstract with commentary and details beyond what is found in the abstract:

J Child Psychol Psychiatry. 2014 May;55(5):485-94. doi: 10.1111/jcpp.12178. Epub 2013 Dec 9.
Predicting young adult outcome among more and less cognitively able individuals with autism spectrum disorders.
Anderson DK1, Liang JW, Lord C.

Abstract
BACKGROUND:
The range of outcomes for young adults with Autism Spectrum Disorders (ASD) and the early childhood factors associated with this diversity have implications for clinicians and scientists.

METHODS:
This prospective study provided a unique opportunity to predict outcome 17 years later for a relatively large sample of children diagnosed with ASD at 2 years old. Diagnostic and psychometric instruments were administered between 2 and 19 with data from 2, 3, and 19 included in this study. Clinicians administered tests without knowledge of previous assessments whenever possible. Caregivers provided additional information through questionnaires.

RESULTS:
Significant intellectual disabilities at 19 were predicted by age 2 about 85% of the time from VIQ and NVIQ scores together, though prediction of young adult outcome for youths with average or higher intelligence was more complex. By 19, 9% of participants had largely overcome core difficulties associated with ASD and no longer retained a diagnosis. These youths with Very Positive Outcomes were more likely to have participated in treatment and had a greater reduction in repetitive behaviors between age 2 and 3 compared to other Cognitively Able youths (VIQ ≥70) with ASD. Very Positive Outcome youths did not differ phenotypically from Cognitively Able ASD individuals at 2 but both groups differed from Cognitively Less Able individuals (VIQ <70).

CONCLUSION:
Those most at risk for intellectual disabilities and ASD can be reliably identified at an early age to receive comprehensive treatment. Findings also suggest that some cognitively able children with ASD who participate in early intervention have very positive outcomes, although replication with randomized, larger samples is needed. In order to improve understanding of very positive outcomes in ASD, future research will need to identify how variations in child characteristics and environmental factors contribute to the nature and timing of growth across individuals and areas of development.
http://www.ncbi.nlm.nih.gov/pubmed/24313878

Full text of study is not open access but these links have additional details and commentary regarding the study:

http://questioning-answers.blogspot.com/2014/02/optimal-outcome-autism-by-any-other-name.html

https://spectrumnews.org/news/early-tests-predict-intellect-in-adults-with-autism/
Winnie
"Make it a powerful memory, the happiest you can remember."

Santosg
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Re: Interesting neuroimaging study regarding Optimal Outcome (indistinguishable from peers, “recovered”)

Postby Santosg » Sun Mar 27, 2016 3:58 am

IQ, in my mind, is a largely meaningless measurement. Yes it might have some validity but not enough to be a useful way of evaluating then capacities of individuals to interact with their environment. honestly the entire purpose of IQ testing is founded in eugenics and is still philosophically entrenched in that outlook. This is true also of individuals that are interested in IQ testing as a professional career path or who put great weight on what these test say.

Speaking to the point you made regarding the non-verbal boy with the average IQ, I think questions of IQ are better stated around the capacity for focused attention.

Some of what we are discussing relates in interesting ways to the philosophy of mind. Are you familiar with the literature? The question of the difference between brain and mental states as well as Jerry Fodor's work regarding multiple realizability jump out.

Winnie
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Re: Interesting neuroimaging study regarding Optimal Outcome (indistinguishable from peers, “recovered”)

Postby Winnie » Mon Mar 28, 2016 5:12 pm

Santosg wrote:IQ, in my mind, is a largely meaningless measurement. Yes it might have some validity but not enough to be a useful way of evaluating then capacities of individuals to interact with their environment.
I agree – IQ tests are often invalid in assessing a child with language disorders, not very useful in planning intervention, and can even affect the perception of a child’s potential in a negative way. In the case of the child I described, the test results were surprising to the school district – many (if not most) people assume that a severely-affected non-verbal child is also intellectually disabled, and they may use this to pass judgment on a child's potential. This should not happen to any child, including a child who does have an intellectual disability.

Santosg wrote:Speaking to the point you made regarding the non-verbal boy with the average IQ, I think questions of IQ are better stated around the capacity for focused attention.
Are you referring to the difference between adaptive functioning and IQ perhaps? I’m not sure what you mean by focused attention.

Santosg wrote:Some of what we are discussing relates in interesting ways to the philosophy of mind. Are you familiar with the literature? The question of the difference between brain and mental states as well as Jerry Fodor's work regarding multiple realizability jump out.
Honestly, I am not familiar enough with the literature in the area of philosophy (or with the debate between specific philosophers’ theories of the mind) to apply this in any meaningful way to autism. Not a discipline I’ve had reason to delve into deeply so far. Thankfully. :)
Winnie
"Make it a powerful memory, the happiest you can remember."


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