Infant social attention: an endophenotype of ASD-related traits?

BACKGROUND: As a neurodevelopmental disorder, symptoms of ASD likely emerge from a complex interaction between preexisting genetic vulnerabilities and the child's environment. One way to understand causal paths to ASD is to identify dimensional ASD-related traits that vary in the general population and that predispose individuals with other risk factors toward ASD. Moving beyond behavioral traits to explore underlying neurocognitive processes may further constrain the underlying genetics. Endophenotypes are quantitative, heritable, trait-related differences that are generally assessed with laboratory-based methods, can be identified in the general population, and may be more closely tied to particular causal chains that have a more restricted set of genetic roots. The most fruitful endophenotypes may be those observed in infancy, prior to the emergence of behavioral symptoms that they are hypothesized to cause. Social motivation is an ASD-related trait that is highly heritable. In this study, we investigate whether infant endophenotypes of social attention relate to familial risk for lower social motivation in the general population. METHODS: We examined whether infant social attention (measured using habituation, EEG power, and event-related potential tasks previously used in infants/toddlers with ASD) varies quantitatively with parental social motivation in 117 six-month-old and 106 twelve-month-old typically developing infants assessed cross-sectionally. To assess heritable aspects of social motivation, primary caregiver biological parents completed two self-report measures of social avoidance and discomfort that have shown high heritability in previous work. RESULTS: Parents with higher social discomfort and avoidance had infants who showed shorter looks to faces but not objects; reduced theta power during naturalistic social attention; and smaller P400 responses to faces versus objects. CONCLUSIONS: Early reductions in social attention are continuously related to lower parental social motivation. Alterations in social attention may be infant endophenotypes of social motivation traits related to ASD.

Developmental changes in infant brain activity during naturalistic social experiences.

Between 6 and 12 months, typically developing infants undergo a socio-cognitive "revolution." The Interactive Specialization (IS) theory of brain development predicts that these behavioral changes will be underpinned by developmental increases in the power and topographic extent of socially selective cortical responses. To test this hypothesis, we used EEG to examine developmental changes in cortical selectivity for ecologically valid dynamic social versus non-social stimuli in a large cohort of 6- and 12-month-old infants. Consistent with the Interactive Specialization model, results showed that differences in EEG Θ activity between social and non-social stimuli became more pronounced and widespread with age. Differences in EEG activity were most clearly elicited by a live naturalistic interaction, suggesting that measuring brain activity in ecologically valid contexts is central to mapping social brain development in infancy.

Developmental change in the ERP responses to familiar faces in toddlers with autism spectrum disorders versus typical development.

Individuals with autism spectrum disorder (ASD) show differences in face processing abilities from early in development. To examine whether these differences reflect an atypical versus delayed developmental trajectory, neural responses to familiar and unfamiliar faces in twenty-four 18- to 47-month-old children with ASD were compared with responses of thirty-two 12- to 30-month-old typically developing children. Results of 2 experiments revealed that neural responses to faces in children with ASD resembled those observed in younger typically developing children, suggesting delayed development. Electrophysiological responses to faces were also related to parent report of adaptive social behaviors for both children with ASD and typical development. Slower development of the face processing system in ASD may be related to reduced self-directed "expected" experience with faces in early development.

A Screening Tool to Measure Eye Contact Avoidance in Boys with Fragile X Syndrome.

We examined the reliability, validity and factor structure of the Eye Contact Avoidance Scale (ECAS), a new 15-item screening tool designed to measure eye contact avoidance in individuals with fragile X syndrome (FXS). Internal consistency of the scale was acceptable to excellent and convergent validity with the Social Responsiveness Scale, Second Edition (SRS-2) and the Anxiety, Depression, and Mood Scale (ADAMS) was good. Boys with a comorbid ASD diagnosis obtained significantly higher scores on the ECAS compared to boys without ASD, when controlling for communication ability. A confirmatory factor analysis indicated that a two-factor model (avoidance and aversion) provided an excellent fit to the data. The ECAS appears to be a promising reliable and valid tool that could be employed as an outcome measure in future pharmacological/behavioral treatment trials for FXS.

Early behavioral intervention is associated with normalized brain activity in young children with autism.

OBJECTIVE: A previously published randomized clinical trial indicated that a developmental behavioral intervention, the Early Start Denver Model (ESDM), resulted in gains in IQ, language, and adaptive behavior of children with autism spectrum disorder. This report describes a secondary outcome measurement from this trial, EEG activity. METHOD: Forty-eight 18- to 30-month-old children with autism spectrum disorder were randomized to receive the ESDM or referral to community intervention for 2 years. After the intervention (age 48 to 77 months), EEG activity (event-related potentials and spectral power) was measured during the presentation of faces versus objects. Age-matched typical children were also assessed. RESULTS: The ESDM group exhibited greater improvements in autism symptoms, IQ, language, and adaptive and social behaviors than the community intervention group. The ESDM group and typical children showed a shorter Nc latency and increased cortical activation (decreased α power and increased θ power) when viewing faces, whereas the community intervention group showed the opposite pattern (shorter latency event-related potential [ERP] and greater cortical activation when viewing objects). Greater cortical activation while viewing faces was associated with improved social behavior. CONCLUSIONS: This was the first trial to demonstrate that early behavioral intervention is associated with normalized patterns of brain activity, which is associated with improvements in social behavior, in young children with autism spectrum disorder.