Functional connectivity during language processing in 3-month-old infants at familial risk for autism spectrum disorder.

Auditory statistical learning (ASL) plays a role in language development and may lay a foundation for later social communication impairment. As part of a longitudinal study of infant siblings, we asked whether electroencephalography (EEG) measures of connectivity during ASL at 3 months of age-differentiated infants who showed signs of autism spectrum disorder (ASD) at age 18 months. We measured spectral power and phase coherence in the theta (4-6 Hz) and alpha (6-12 Hz) frequency bands within putative language networks. Infants were divided into ASD-concern (n = 14) and No-ASD-concern (n = 49) outcome groups based on their ASD symptoms at 18 months, measured using the Autism Diagnostic Observation Scale Toddler Module. Using permutation testing, we identified a trend toward reduced left fronto-central phase coherence at the electrode pair F9-C3 in both theta and alpha frequency bands in infants who later showed ASD symptoms at 18 months. Across outcome groups, alpha coherence at 3 months correlated with greater word production at 18 months on the MacArthur-Bates Communicative Development Inventory. This study introduces signal processing and analytic tools that account for the challenges inherent in infant EEG studies, such as short duration of recordings, considerable movement artifact, and variable volume conduction. Our results indicate that connectivity, as measured by phase coherence during 2.5 min of ASL, can be quantified as early as 3 months and suggest that early alternations in connectivity may serve as markers of resilience for neurodevelopmental impairments.

Early developmental trajectories associated with ASD in infants with tuberous sclerosis complex.

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.