Objective

We performed a longitudinal cohort study of infants with tuberous sclerosis complex (TSC), with the overarching goal of defining early clinical, behavioral, and biological markers of autism spectrum disorder (ASD) in this high-risk population.

Methods

Infants with TSC and typically developing controls were recruited as early as 3 months of age and followed longitudinally until 36 months of age. Data gathered at each time point included detailed seizure history, developmental testing using the Mullen Scales of Early Learning, and social-communication assessments using the Autism Observation Scale for Infants. At 18 to 36 months, a diagnostic evaluation for ASD was performed using the Autism Diagnostic Observation Schedule.

Results

Infants with TSC demonstrated delays confined to nonverbal abilities, particularly in the visual domain, which then generalized to more global delays by age 9 months. Twenty-two of 40 infants with TSC were diagnosed with ASD. Both 12-month cognitive ability and developmental trajectories over the second and third years of life differentiated the groups. By 12 months of age, the ASD group demonstrated significantly greater cognitive delays and a significant decline in nonverbal IQ from 12 to 36 months.

Conclusions

This prospective study characterizes early developmental markers of ASD in infants with TSC. The early delay in visual reception and fine motor ability in the TSC group as a whole, coupled with the decline in nonverbal ability in infants diagnosed with ASD, suggests a domain-specific pathway to ASD that can inform more targeted interventions for these high-risk infants.

Statistical learning is characterized by detection of regularities in one's environment without an awareness or intention to learn, and it may play a critical role in language and social behavior. Accordingly, in this study we investigated the electrophysiological correlates of visual statistical learning in young children with autism spectrum disorder (ASD) using an event-related potential shape learning paradigm, and we examined the relation between visual statistical learning and cognitive function. Compared to typically developing (TD) controls, the ASD group as a whole showed reduced evidence of learning as defined by N1 (early visual discrimination) and P300 (attention to novelty) components. Upon further analysis, in the ASD group there was a positive correlation between N1 amplitude difference and non-verbal IQ, and a positive correlation between P300 amplitude difference and adaptive social function. Children with ASD and a high non-verbal IQ and high adaptive social function demonstrated a distinctive pattern of learning. This is the first study to identify electrophysiological markers of visual statistical learning in children with ASD. Through this work we have demonstrated heterogeneity in statistical learning in ASD that maps onto non-verbal cognition and adaptive social function.