Autism spectrum disorder (ASD) can produce strikingly different clinical outcomes in young children, with some having strong conversation abilities and others not talking at all. A study published by Cell Press April 9th in Neuron reveals the reason: At the very first signs of possible autism in infants and toddlers, neural activity in language-sensitive brain regions is already similar to normal in those ASD toddlers who eventually go on to develop good language ability but nearly absent in those who later have a poor language outcome.
"Why some toddlers with ASD get better and develop good language and others do not has been a mystery that is of the utmost importance to solve," says senior author Eric Courchesne, co-director of the UC San Diego Autism Center, where the study was designed and conducted. "Discovering the early neural bases for these different developmental trajectories now opens new avenues to finding causes and treatments specific to these two very different subtypes of autism."
The researchers studied 60 ASD and 43 non-ASD infants and toddlers using the natural sleep functional magnetic resonance imaging (fMRI) method developed by the UCSD Autism Center investigators to record brain activity in the participants as they listened to excerpts from children's stories. All toddlers were clinically followed until early childhood to make a final determination of which ones eventually had good versus poor language outcomes.
In ASD, good language outcomes by early childhood were preceded by normal patterns of neural activity in language-sensitive brain regions, including superior temporal cortex, during infant and toddler ages. By contrast, ASD children with poor language outcomes showed very little activity in superior temporal cortex when they were toddlers or infants.
"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," says first author Michael Lombardo of the University of Cyprus.
The researchers also found that, when combined with behavioral tests, these striking early neural differences may help predict later language outcome by early childhood. The prognostic accuracy of the combined neural and behavioral measures was 80%, compared with 68% for each measure alone. "One of the first things parents of a toddler with ASD want to know is what lies ahead for their child," says co-author Karen Pierce, also co-director of the UC San Diego Autism Center. "These findings open insight into the first steps that lead to different clinical and treatment outcomes, and in the future, one can imagine clinical evaluation and treatment planning incorporating multiple accurate behavioral and medical prognostic assessments. That would be a huge practical benefit for families."
Moving forward, the researchers will further investigate the early neural functional substrates that precede and underlie language and social heterogeneity in ASD. They also plan to test the idea that activation, or its absence, in language cortex predicts treatment responsiveness in toddlers with ASD. Moreover, future research on the molecular underpinnings of variable clinical outcomes in individuals with ASD could pave the way for the development of novel pharmacological interventions. "Understanding that there are discrete subgroups of early developing ASD that are distinguished by developmental behavioral trajectories, neural underpinnings, and brain-behavioral relationships, really lays the groundwork for a whole range of really fruitful directions," Lombardo says.
This work was supported by the National Institute of Mental Health, the National Foundation for Autism Research, and fellowships from Jesus College, Cambridge and the British Academy.
Neuron, Lombardo et al.: "Different functional neural substrates for good and poor language outcome in autism" http://dx.doi.org/10.1016/j.neuron.2015.03.023
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