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Heterogeneity of neural mechanisms of response to pivotal response treatment

  • SI: Developing Brain
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Abstract

We investigated the mechanisms by which Pivotal Response Treatment (PRT) improves social communication in a case series of 10 preschool-aged children with Autism Spectrum Disorder (ASD). Functional magnetic resonance imaging (fMRI) identified brain responses during a biological motion perception task conducted prior to and following 16 weeks of PRT treatment. Overall, the neural systems supporting social perception in these 10 children were malleable through implementation of PRT; following treatment, neural responses were more similar to those of typically developing children (TD). However, at baseline, half of the children exhibited hypoactivation, relative to a group of TD children, in the right posterior superior temporal sulcus (pSTS), and half exhibited hyperactivation in this region. Strikingly, the groups exhibited differential neural responses to treatment: The five children who exhibited hypoactivation at baseline evidenced increased activation in components of the reward system including the ventral striatum and putamen. The five children who exhibited hyperactivation at baseline evidenced decreased activation in subcortical regions critical for regulating the flow of stimulation and conveying signals of salience to the cortex—the thalamus, amygdala, and hippocampus. Our results support further investigation into the differential effects of particular treatment strategies relative to specific neural targets. Identification of treatment strategies that address the patterns of neural vulnerability unique to each patient is consistent with the priority of creating individually tailored interventions customized to the behavioral and neural characteristics of a given person.

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Acknowledgments

We would like to thank the Deitz Family for funding this research, and acknowledge additional support from Esme Usdan and family, the Hilibrand Autism Fellowship, the Harris Professorship at the Yale Child Study Center given to Kevin Archer Pelphrey, Allied World, and the Autism Science Foundation. This work is also supported in part by the Yale University Biomedical High Performance Computing Center (NIH grants RR19895 and RR029676-01). We wish to thank the families of the children included in this study for their time and participation. We also wish to thank our colleagues Cara Keifer, Avery Voos, Jonathan Tirrell, Laura Anderson, and Cara Cordeaux for their contributions to the treatment work and clinical characterization of the sample.

Conflict of interest

Pamela Ventola, Daniel Yang, Hannah Friedman, Devon Oosting, Julie Wolf, Denis Sukhodolsky, and Kevin A. Pelphrey declare that they have no conflict of interest.

Informed consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of investigation. Informed consent was obtained from the parents of all patients and verbal assent was obtained from all of the children.

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  1. Center for Translational Developmental Neuroscience, Yale Child Study Center, Yale University, 230 South Frontage Road, PO Box 207900, New Haven, CT, 06520-7900, USA

    Pamela Ventola, Daniel Y. J. Yang, Hannah E. Friedman, Devon Oosting, Julie Wolf, Denis G. Sukhodolsky & Kevin A. Pelphrey

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  1. Pamela Ventola
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  2. Daniel Y. J. Yang
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Correspondence to Pamela Ventola.

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Ventola, P., Yang, D.Y.J., Friedman, H.E. et al. Heterogeneity of neural mechanisms of response to pivotal response treatment. Brain Imaging and Behavior 9, 74–88 (2015). https://doi.org/10.1007/s11682-014-9331-y

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