The Autism Biomarkers Consortium for Clinical Trials: evaluation of a battery of candidate eye-tracking biomarkers for use in autism clinical trials

Molecular Autism

Research

Kelsey J. Dommer¹  Frederick Shic²  Adham Atyabi³  Sara J. Webb⁴  Beibin Li⁵  Erin C. Barney⁶  Gerhard Helleman⁷  Damla Senturk⁸  Catherine A. Sugar⁹  April R. Levin^1,10  Raphael Bernier^1,11  Scott P. Johnson^1,12  Minah Kim^1,13  Shou An Chang^1,14  Shafali Spurling Jeste^1,15  Maura Sabatos-DeVito^1,16  Geraldine Dawson^1,16  James Dziura^1,17  Susan Faja^1,18  Charles A. Nelson^1,19  Michael Murias^2,20  Takumi McAllister^2,21  Adam J. Naples^2,21  Helen Seow^2,21  James C. McPartland^2,21  Simone Hasselmo^2,21  Katarzyna Charwaska^2,21  Quan Wang^2,21 

[1] Center for Child Health, Behavior, and Development, Seattle Children’s Research Institute, 1920 Terry Ave, 98101, Seattle, WA, USA;Center for Child Health, Behavior, and Development, Seattle Children’s Research Institute, 1920 Terry Ave, 98101, Seattle, WA, USA;Department of General Pediatrics, University of Washington School of Medicine, Seattle, WA, USA;Center for Child Health, Behavior, and Development, Seattle Children’s Research Institute, 1920 Terry Ave, 98101, Seattle, WA, USA;Department of General Pediatrics, University of Washington School of Medicine, Seattle, WA, USA;Department of Computer Science, University of Colorado - Colorado Springs, Colorado Springs, CO, USA;Center for Child Health, Behavior, and Development, Seattle Children’s Research Institute, 1920 Terry Ave, 98101, Seattle, WA, USA;Department of Psychiatry and Behavioral Science, University of Washington School of Medicine, Seattle, WA, USA;Center for Child Health, Behavior, and Development, Seattle Children’s Research Institute, 1920 Terry Ave, 98101, Seattle, WA, USA;Paul G. Allen School of Computer Science and Engineering, University of Washington, Seattle, WA, USA;Center for Child Health, Behavior, and Development, Seattle Children’s Research Institute, 1920 Terry Ave, 98101, Seattle, WA, USA;Yale Child Study Center, Yale University School of Medicine, 230 South Frontage Road, 06520, New Haven, CT, USA;Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA;Department of Biostatistics, University of California Los Angeles, Los Angeles, CA, USA;Department of Biostatistics, University of California Los Angeles, Los Angeles, CA, USA;Division of Neurology, Department of Pediatrics, Children’s Hospital Los Angeles, Los Angeles, CA, USA;Department of Neurology, Boston Children’s Hospital, Boston, MA, USA;Harvard Medical School, Boston, MA, USA;Department of Psychiatry and Behavioral Science, University of Washington School of Medicine, Seattle, WA, USA;Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA;Department of Psychology, University of Virginia, P.O. Box 400400, 102 Gilmer Hall, 22904, Charlottesville, VA, USA;Department of Psychology, Yale University, 2 Hillhouse Ave, 06520, New Haven, CT, USA;Division of Neurology, Department of Pediatrics, Children’s Hospital Los Angeles, Los Angeles, CA, USA;Duke Center for Autism and Brain Development, Duke University, Durham, NC, USA;Emergency Medicine, Yale University School of Medicine, New Haven, CT, USA;Harvard Medical School, Boston, MA, USA;Department of Pediatrics, Boston Children’s Hospital, Boston, MA, USA;Harvard Medical School, Boston, MA, USA;Department of Pediatrics, Boston Children’s Hospital, Boston, MA, USA;Graduate School of Education, Harvard University, Boston, MA, USA;Institute for Innovations in Developmental Sciences, Northwestern University, Chicago, IL, USA;Yale Child Study Center, Yale University School of Medicine, 230 South Frontage Road, 06520, New Haven, CT, USA;

关键词: Autism spectrum disorder;    Biomarkers;    Eye tracking;    Visual attention;    Face processing;    Biological motion;    Gaze pattern;   

DOI  :  10.1186/s13229-021-00482-2

 received in 2021-07-05, accepted in 2021-12-20,  发布年份 2021

来源: Springer

【 摘 要 】

BackgroundEye tracking (ET) is a powerful methodology for studying attentional processes through quantification of eye movements. The precision, usability, and cost-effectiveness of ET render it a promising platform for developing biomarkers for use in clinical trials for autism spectrum disorder (ASD).MethodsThe Autism Biomarkers Consortium for Clinical Trials conducted a multisite, observational study of 6–11-year-old children with ASD (n = 280) and typical development (TD, n = 119). The ET battery included: Activity Monitoring, Social Interactive, Static Social Scenes, Biological Motion Preference, and Pupillary Light Reflex tasks. A priori, gaze to faces in Activity Monitoring, Social Interactive, and Static Social Scenes tasks were aggregated into an Oculomotor Index of Gaze to Human Faces (OMI) as the primary outcome measure. This work reports on fundamental biomarker properties (data acquisition rates, construct validity, six-week stability, group discrimination, and clinical relationships) derived from these assays that serve as a base for subsequent development of clinical trial biomarker applications.ResultsAll tasks exhibited excellent acquisition rates, met expectations for construct validity, had moderate or high six-week stabilities, and highlighted subsets of the ASD group with distinct biomarker performance. Within ASD, higher OMI was associated with increased memory for faces, decreased autism symptom severity, and higher verbal IQ and pragmatic communication skills.LimitationsNo specific interventions were administered in this study, limiting information about how ET biomarkers track or predict outcomes in response to treatment. This study did not consider co-occurrence of psychiatric conditions nor specificity in comparison with non-ASD special populations, therefore limiting our understanding of the applicability of outcomes to specific clinical contexts-of-use. Research-grade protocols and equipment were used; further studies are needed to explore deployment in less standardized contexts.ConclusionsAll ET tasks met expectations regarding biomarker properties, with strongest performance for tasks associated with attention to human faces and weakest performance associated with biological motion preference. Based on these data, the OMI has been accepted to the FDA’s Biomarker Qualification program, providing a path for advancing efforts to develop biomarkers for use in clinical trials.

【 授权许可】

CC BY   
© The Author(s) 2022. corrected publication 2022

【 图 表 】

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