Experimental Techniques for Early Identification of Autism

Study Overview
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Brief Summary
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This project deals with essential challenges in the context of Autism Spectrum Disorder, benefiting from a longitudinal design in infancy and a cutting-edge electroencephalogram/eye-tracking integrated approach. The investigators will focus on multisensory audiovisual integration to identify early markers of autism in infants at-risk for autism. The investigators will characterize early derailments from the typical developmental trajectories to identify critical time windows and better describe the heterogeneity of autism.

Detailed Description
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Autism Spectrum Disorder is a heterogeneous condition characterized by atypical social communication and repetitive patterns of behavior, with recent Italian prevalence estimates of one in 77. The heterogeneity of autism is expressed in individual variation not only in the severity of core symptoms but also in cognitive, language, and behavioral skills, which show different developmental trajectories. Moreover, there is a strong interest in identifying reliable behavioral and brain-based predictors, which may constitute useful tools for early detection of at-risk cases. In particular, autistic individuals perform poorly during conditions that require integration across multiple sensory modalities such as audiovisual sensory integration, and process differently social and non-social stimuli compared to neurotypical counterparts. However, the study of potential interaction between sensory and social processing in the first years of life is still scarce. No study examined early social and sensory markers in infant siblings of autistic children using integrated experimental techniques. The study includes siblings of autistic children and neurotypical toddlers recruited at 18 months and a follow-up evaluation is collected at 24 months. At both time-points, all children are assessed with an experimental protocol, including behavioral and neurophysiological measures. The integrated electroencephalogram -eyetracking task focuses on sensory processing in social (face saying wow in infant-directed speech) and non-social (spinning top toy) conditions. Presented videos are presented both in synchronous and asynchronous modalities (1000 ms delay audio presentation). Electroencephalographic signal is recorded by High-Density 128-channel system and pupil dilations are recorded using a Tobii ProSpectrum 300 Hertz system. In addition, complete information about clinical measures is collected for all children at 18 and 24 months.

Official Title
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Early Identification of Autism Spectrum Disorder: Towards an Integrated Biomarker Approach

Conditions
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Autism Spectrum Disorder, Infant Development

Intervention / Treatment
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* Behavioral: Neurodevelopmental assessment
* Other: Electrophysiological and eyetracking recordings


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants aged between 6 and 36 months Toddlers at elevated likelihood of developing autism because siblings of children with autism Exclusion Criteria: gestational age <36 weeks Griffiths general quotient < 70 presence of major complications in pregnancy and/or delivery likely to affect brain development presence of neurological deficits, dysmorphic markers, or other medical conditions

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 36 Months

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Infant siblings of children with autism spectrum disorder<br> | Behavioral: Neurodevelopmental assessment<br>* individual behavioral and socio-communicative assessment from 6 to 36 months<br>Other: Electrophysiological and eyetracking recordings<br>* Investigation of neural and behavioral biomarkers of autism from 6 to 24 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive outcome of standardized tests | standardized scores (i.e., Intelligence quotient scores) of Griffiths scales will be measured and will be correlated with electroencephalographic and eyetracking parameters | age 36 months | 
| Socio-communicative outcome of standardized tests | standardized scores (Calibrated severity scores) of Autism Diagnostic Observation Schedule - 2 edition (Social Affect, Restricted/Repetitive behaviors) will be measured and will be correlated with electroencephalographic and eyetracking parameters | age 36 months | 
| Sensory outcome of standardized tests | standardized scores (i.e., z-scores) of sensory profile-2 (sensory seeking, avoiding, sensitivity, registration) will be measured and will be correlated with electroencephalographic and eyetracking parameters | age 36 months | 
| Change of electroencephalografic theta power and looking behavior during development | Electroencephalographic theta power, looking behavior (time of fixation in different areas of interest, pupillometry parameters) to synchronous/asynchronous audio-visual stimuli will be measured longitudinally. | at 6, 12, 18 and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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siblings, biomarker, autism, infants