Why do some children in the spectrum of autism disorder develop greater difficulties with language than others?
Discovering the neural basis of why some children with autism spectrum disorder (ASD) get better and develop good language and conversation abilities, and others do not, has been a research mystery of "utmost importance."
And the new findings, achieved through functional MRI (fMRI) brain imaging, open up new avenues for the causes and treatment of autism, say the researchers publishing in the journal Neuron.
The functional neuroimaging findings amount to a "discovery" on early language development in autism, say the authors in the research paper.
Language is an area of variation in the children that is "one of the theoretically and clinically most important," write the authors - and prior to their work, neurobiological explanations were "lacking" for why toddlers and young children with ASD go along such different clinical courses.
Talking to Medical News Today, coauthor Eric Courchesne, PhD, when asked how this finding was powerful, reiterated the paper: "First and foremost, the central and immediate power of this study and finding is discovery of the neural developmental reason for good and poor language and clinical outcome in autism.
"This is a major finding because this has been a complete mystery before this study."
Dr Courchesne - a director at the autism center of excellence in La Jolla, CA, part of the UC San Diego School of Medicine - described how this study could prove to be one of the leading examples of many that go on to utilize the "power of brain imaging in autism."
First author Michael Lombardo, PhD - of the University of Cyprus, and honorary senior researcher for the autism research center of the psychiatry department of the University of Cambridge - adds:
"Our study is important because it's one of the first large-scale studies to identify very early neural precursors that help to differentiate later emerging and clinically relevant heterogeneity in early language development in ASD toddlers."
Co-author Karen Pierce, PhD, also introduces the potential clinical relevance of this line of research for families:
"One of the first things parents of a toddler with ASD want to know is what lies ahead for their child.
These findings open insight into the first steps that lead to different clinical and treatment outcomes."
Dr. Pierce, associate professor in neuroscience and also a director at the UC San Diego autism center, adds that, in the future, "one can imagine clinical evaluation and treatment planning incorporating multiple accurate behavioral and medical prognostic assessments." She concludes:
"That would be a huge practical benefit for families."
Brain activity scanned while children listened to stories
The researchers' conducted brain scans during the children's natural sleep. They measured "passive speech comprehension" during simple and complex voice recordings.
The researchers used their natural sleep functional magnetic resonance imaging (fMRI) method to study what is a large group for such work - 60 infants and toddlers with ASD and 43 non-ASD controls.
The investigators recorded brain activity while the participants listened to excerpts from children's stories - an approach they dubbed the "story language paradigm." Three types of speech stimuli were used to measure passive speech comprehension under fMRI:
- Complex forward speech
- Simple forward speech
- Backward speech.
All the toddlers in the study were followed up until early childhood to determine which of them eventually had good versus poor language outcomes. Assessments of their language, nonverbal and autism symptom development were made around every 6 months.
The prognostic accuracy reached 80% when the fMRI measures of the "striking early neural differences" were added to behavioral tests. This was compared with 68% accuracy for each measure alone.
Would fMRI scanning really prove practical in ASD?
Dr. Courchesne added further claim to the potential practicality of functional brain imaging. He told MNT:
"I think fMRI can be highly useful for treatment research and, in the future, highly useful for treatment planning. And practical! Only those who have not done natural sleep imaging of infants think this is impractical."
"I have personally imaged over 1,000 babies and toddlers, and it is not difficult," he added. "Our story language test takes 6 minutes of fMRI scan time during natural sleep and is inexpensive."
Dr. Courchesne added that presently in the US, the national medical recommendation was for structural MRI scanning of toddlers or children with autism, "yet MRI is seldom informationally useful."
He envisioned a future for the application of fMRI - and its ability to see live brain activity related to language - as a test of toddlers after a diagnosis of autism has already been made. This would not be as a screen, but as a follow-up evaluation - "to determine brain-responsiveness to speech and possible treatment-readiness for one or another different treatment approach."
However, Dr. Sarah Burnett, a consultant general radiologist working in London, UK, reminds us of the present cost of imaging, and citing the example of Europe, how research hopes for fMRI would need to see a continuation of the changes to the way ASD is diagnosed. She says:
"Whilst this is a fascinating piece of early research, its practical implications remain to be seen. There has recently been a Europe-wide redefinition of autistic spectrum disorders, and this may prove very useful to place children more accurately on that spectrum, given that the diagnosis is currently clinical."
The number of people with ASD means "the price implications [of scans] may be enormous." In the US, CDC statistics show the number of children diagnosed with ASD translates into an estimated 1 in every 68 children.
Research importance and the 'omnibus label of autism'
Dr. Courchesne said that while it was a "long way off," his view was that "our finding has potentially direct clinical relevance, and as functional imaging moves towards the day when it is used, especially in fetal, neonatal and early developmental clinical situations, this finding will likely stand as one that will be guide future designs for clinical application."
The 'label' of autism covers a wide range of children.
Dr. Lombardo also gave MNT some of his thoughts about the power of this type of brain scanning:
"fMRI is one of the most powerful methods we currently have for making noninvasive in-vivo measurements and inferences about brain function in living patients.
"With that being said, the way one can apply the method varies based on each individual researcher's specific question, and sometimes those questions end up not having that much clinical impact, while other times the usage of fMRI is very insightful and clinically very relevant."
The Neuron study strived "to apply the method in a way that allows us to answer some clinically very important questions."
The key point of the study was to ask whether subgroups of ASD that are different behaviorally and developmentally in terms of language development, might also be differentiated neurally. Dr Lombardo added:
"By discovering these ways of stratifying the heterogeneous individuals underneath an omnibus label like 'autism', this will hopefully enable future work to better hone in on biological mechanisms that may be relevant for targeting in novel kinds of treatments."
Dr Lombardo also agreed, however, that these implications were "a bit off in the future at this point." But making a "strong case for distinct kinds of subtypes for autism" could spur on "new insights that have much clinic impact for patients and families."
Complexities and controversies of understanding autism
Autism spectrum disorders are complex and include a range of developmental problems. Research into causes and treatments is also complex and wide-ranging, and receives a lot of attention.
One area of interest is a link to the gut. Evidence emerged in March, for example, that many young children with autism show gut symptoms - gastrointestinal symptoms of constipation, diarrhea and food allergy/intolerance were more likely to be reported by their mothers than by those of infants with typical development.
Also in March was the separate story of a man whose son with autism appeared to show improvement following a course of antibiotics. The individual case study - described by the father with a background in molecular biology and an interest in funding neglected areas of research into "fundamental biological mechanisms of autism" - has attracted much interest.
April is the Autism Society's national autism awareness month, so MNT has produced an overview of some of the controversies and plain myths surrounding autism spectrum disorder - for example, the myth that all people with ASD have a "special gift" or the damaging myth that people with ASD do not have feelings.