Monday, November 28, 2016

fMRI biomarkers predicting response to pivotal response treatment in autism

Yang D, Pelphrey KA, Sukhodolsky DG, Crowley MJ, Dayan E, Dvornek NC, Venkataraman A, Duncan J, Staib L, Ventola P. Brain responses to biological motion predict treatment outcome in young children with autism. Transl Psychiatry. 2016 Nov 15;6(11):e948.

Autism spectrum disorders (ASDs) are common yet complex neurodevelopmental disorders, characterized by social, communication and behavioral deficits. Behavioral interventions have shown favorable results-however, the promise of precision medicine in ASD is hampered by a lack of sensitive, objective neurobiological markers (neurobiomarkers) to identify subgroups of young children likely to respond to specific treatments. Such neurobiomarkers are essential because early childhood provides a sensitive window of opportunity for intervention, while unsuccessful intervention is costly to children, families and society. In young children with ASD, we show that functional magnetic resonance imaging-based stratification neurobiomarkers accurately predict responses to an evidence-based behavioral treatment-pivotal response treatment. Neural predictors were identified in the pretreatment levels of activity in response to biological vs scrambled motion in the neural circuits that support social information processing (superior temporal sulcus, fusiform gyrus, amygdala, inferior parietal cortex and superior parietal lobule) and social motivation/reward (orbitofrontal cortex, insula, putamen, pallidum and ventral striatum). The predictive value of our findings for individual children with ASD was supported by a multivariate pattern analysis with cross validation. Predicting who will respond to a particular treatment for ASD, we believe the current findings mark the very first evidence of prediction/stratification biomarkers in young children with ASD. The implications of the findings are far reaching and should greatly accelerate progress toward more precise and effective treatments for core deficits in ASD.

"We [currently] have no way to predict a child's outcome and to match a child to a particular intervention or determine which children have the best chance to respond to a particular treatment," Dr Ventola told Medscape Medical News.

The researchers investigated the accuracy of fMRI neurobiomarkers in predicting response to [pivotal response treatment] PRT in seven girls and 13 boys with ASD (mean age, 5.9 years).

PRT includes parental training and uses motivational play activities to boost the development of social communications skills.

For the study, the researchers used a well-validated biological motion fMRI paradigm that "robustly" engages the neural circuits supporting social motivation and social information processing.

They discovered a brain network in which the pretreatment brain activities that are engaged during biological motion viewing predicted response to PRT.

"Specifically, the network includes key brain regions supporting social information processing (the superior temporal sulcus region, fusiform gyrus, superior parietal lobule) and social motivation (orbitofrontal cortex, putamen, ventral striatum)," the researchers report.

"Critically," they note, the results were supported by multivariate pattern analysis, which utilized a standard cross validation framework, "suggesting that the patterns of brain activities across these brain regions may serve as robust predictive biomarkers, generalizable to new, unseen participants."

"This discovery might lead to further development of precision medicine in ASD," lead author Daniel Y. J. Yang, PhD, previously of Yale University, now with the Autism and Neurodevelopmental Disorders Institute, the George Washington University and Children's National Health System, in Washington, DC, told Medscape Medical News.
For example, pretreatment fMRI or electroencephalography "may be used to facilitate the fitting process when families want to identify appropriate and effective treatments for their children," he explained.

"For children who might not be able to benefit immediately from the treatment, theoretically, if we can increase the pretreatment activation and their brain readiness to respond (eg, by oxytocin), we can increase the treatment effectiveness for these children," Dr Yang said.

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