Discovering Eye Tracking Biomarkers of ASD with Diagnostic and Prognostic Power

发现具有诊断和预后能力的 ASD 眼动追踪生物标志物

• 批准号: 10532198
• 负责人: Karen L Pierce
• 金额: $ 71.26万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10532198
• 关键词: 3 year old; 4 year old; Address; Age; Area; Attention; Auditory; Biological Markers; Child; Childhood; Clinical; Cluster Analysis; Cognition; Cognitive; Collaborations; Computer software; Data; Detection; Development; Developmental Delay Disorders; Diagnosis; Diagnostic; Disease; Early Diagnosis; Emotional; Equipment; Eye Development; Face; Frequencies; Funding; Future; General Population; Gold; Grant; Heterogeneity; Image; Individual; Language; Link; National Institute of Mental Health; Neurodevelopmental Disorder; Ocular Fixation; Parents; Pattern; Performance; Play; Predictive Value; Procedures; Prognosis; Prognostic Marker; Reporting; Reproducibility; Research; Research Personnel; Risk; Role; Sample Size; Sampling; Science; Scientist; Severities; Siblings; Signs and Symptoms; Site; Specificity; Speech; Standardization; Symptoms; Technology; Testing; Toddler; Visual; Washington; artificial neural network; autism spectrum disorder; autistic children; checkup examination; cohort; design; diagnostic accuracy; diagnostic biomarker; diagnostic signature; diagnostic value; disorder subtype; feature selection; gaze; individualized medicine; innovation; interest; joint attention; population based; prognostic; prognostic signature; prognostic value; programs; recruit; sample fixation; screening; social; social attention; standard of care; success; trait; visual tracking

Children with ASD, on average, are not identified and treated until around age 4‐years, several years beyond the first signs and symptoms. Even when toddlers are diagnosed as ASD, parents and clinicians have little information to guide treatment decisions or predict the early course of that child's next few years. Research is needed to discover objective biomarkers that detect ASD at early ages with high accuracy, indicate disorder subtypes linked to definable clinical profiles, and convey prognostic information. The discovery of such biomarkers have been elusive, in part, because most studies utilize small sample sizes and fail to include non‐ASD delay contrast groups which are essential to enhance specificity. Our proposal plans to fill this gap by leveraging eye tracking technology to determine if visual fixation patterns in a large sample of very young (12‐36 months) ASD and non‐ASD toddlers (n=225) from the general population can be used to discover an eye tracking biomarker profile of ASD. The prognostic power of our eye tracking biomarkers will be determined by linking initial eye tracking scores to clinical profiles 1‐2 years later. Given the heterogeneity in ASD, it is unlikely that a single eye tracking test would detect all toddlers. Here we plan to remedy this by testing the utility of a battery of 9 developmentally appropriate, short (~1‐minute each), eye tracking tests that each tap into a foundational domain in ASD symptoms including: visual social attention, gaze shifting, and auditory social attention. Our tests will objectively quantify key metrics such as overall fixation levels within social versus non‐social images, the frequency of gaze alterations during joint attention and gaze following tests and, using unique gaze contingent technology, the degree to which a toddler prefers to listen to prosodic, emotionally valent, motherese speech. Our preliminary findings suggest that several of our proposed eye tracking tests have extremely high diagnostic accuracy. Findings, however, are sometimes not replicated in science, and we proactively address this by proposing concurrent, independent and exact (equipment, software, paradigms, procedures) replication testing of each of our eye tracking tests within an independent cohort of toddlers at U. Washington (n=90 toddlers). Thus, in AIM 1 we will discover an eye tracking biomarker that detects ASD at early ages (12‐36 months) with high accuracy using artificial neural networks at UCSD, and then we will independently test replication of its performance at U Washington. To enhance interpretability, our approach will incorporate patterns of metrics from each eye tracking test to produce an Autism Risk Score (ARS) scaled from 0‐100 that represents the level of ASD risk for a toddler. In AIM 2, using a rich clinical battery that captures each toddler's social, language, cognitive and symptom severity profile derived from a combination of standardized, parent report, and free‐play testing, we will identify clinically meaningful eye‐tracking based subtypes of ASD using unbiased network clustering approaches. In AIM 3 we will examine the prognostic utility of our eye tracking test battery by identifying the degree to which eye tracking‐based profiles at ages 12‐36 months can predict social, language, cognitive and attention abilities 1‐2 years later.

平均而言，患有自闭症谱系障碍的儿童直到4岁左右才被发现和治疗，这比正常年龄要晚好几年

项目成果

Level of Attention to Motherese Speech as an Early Marker of Autism Spectrum Disorder.

• DOI: 10.1001/jamanetworkopen.2022.55125
• 发表时间: 2023-02-01
• 期刊: JAMA NETWORK OPEN
• 影响因子: 13.8
• 作者: Pierce, Karen;Wen, Teresa H.;Zahiri, Javad;Andreason, Charlene;Courchesne, Eric;Barnes, Cynthia C.;Lopez, Linda;Arias, Steven J.;Esquivel, Ahtziry;Cheng, Amanda
• 通讯作者: Cheng, Amanda

Large scale validation of an early-age eye-tracking biomarker of an autism spectrum disorder subtype.

• DOI: 10.1038/s41598-022-08102-6
• 发表时间: 2022-03-11
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Wen TH;Cheng A;Andreason C;Zahiri J;Xiao Y;Xu R;Bao B;Courchesne E;Barnes CC;Arias SJ;Pierce K
• 通讯作者: Pierce K

Atypical functional connectivity of temporal cortex with precuneus and visual regions may be an early-age signature of ASD.

• DOI: 10.1186/s13229-023-00543-8
• 发表时间: 2023-03-10
• 期刊: Molecular autism
• 影响因子: 6.2

Neural responses to affective speech, including motherese, map onto clinical and social eye tracking profiles in toddlers with ASD.

对情感言语（包括母亲语）的神经反应映射到患有自闭症谱系障碍（ASD）幼儿的临床和社交眼动追踪档案。

• DOI: 10.1038/s41562-021-01237-y
• 发表时间: 2022
• 期刊: Nature human behaviour
• 影响因子: 29.9
• 作者: Xiao,Yaqiong;Wen,TeresaH;Kupis,Lauren;Eyler,LisaT;Goel,Disha;Vaux,Keith;Lombardo,MichaelV;Lewis,NathanE;Pierce,Karen;Courchesne,Eric
• 通讯作者: Courchesne,Eric