Atypical cerebellar functional connectivity at 9 months of age predicts delayed socio-communicative profiles in infants at high and low risk for autism.

BACKGROUND: While the cerebellum is traditionally known for its role in sensorimotor control, emerging research shows that particular subregions, such as right Crus I (RCrusI), support language and social processing. Indeed, cerebellar atypicalities are commonly reported in autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by socio-communicative impairments. However, the cerebellum's contribution to early socio-communicative development remains virtually unknown. METHODS: Here, we characterized functional connectivity within cerebro-cerebellar networks implicated in language/social functions in 9-month-old infants who exhibit distinct 3-year socio-communicative developmental profiles. We employed a data-driven clustering approach to stratify our sample of infants at high (n = 82) and low (n = 37) familial risk for ASD into three cohorts-Delayed, Late-Blooming, and Typical-who showed unique socio-communicative trajectories. We then compared the cohorts on indices of language and social development. Seed-based functional connectivity analyses with RCrusI were conducted on infants with fMRI data (n = 66). Cohorts were compared on connectivity estimates from a-priori regions, selected on the basis of reported coactivation with RCrusI during language/social tasks. RESULTS: The three trajectory-based cohorts broadly differed in social communication development, as evidenced by robust differences on numerous indices of language and social skills. Importantly, at 9 months, the cohorts showed striking differences in cerebro-cerebellar circuits implicated in language/social functions. For all regions examined, the Delayed cohort exhibited significantly weaker RCrusI connectivity compared to both the Late-Blooming and Typical cohorts, with no significant differences between the latter cohorts. CONCLUSIONS: We show that hypoconnectivity within distinct cerebro-cerebellar networks in infancy predicts altered socio-communicative development before delays overtly manifest, which may be relevant for early detection and intervention. As the cerebellum is implicated in prediction, our findings point to probabilistic learning as a potential intermediary mechanism that may be disrupted in infancy, cascading into alterations in social communication.

Early concerns in parents of infants at risk for autism.

AIM: To examine parental concerns about children at increased familial risk (i.e. high risk) of developing autism spectrum disorder (ASD) in early infancy. METHOD: ASD-related and general parental concerns were prospectively collected for 76 infants at ages 1.5, 3, 6, 9, 12, and 18 months. Outcome classification was determined at 36 months. Analyses included generalized linear mixed models and qualitative evaluation of parental concerns in relation to risk status (high vs low risk) and outcome classification within the high-risk group (atypically developing vs typically developing) over time. RESULTS: Most parents had no concerns at 1.5 (high risk 71%, low risk 87%) and 3 months (high risk 77%, low risk 86%). Beginning at 6 months, parents of high-risk infants reported more ASD-related (p<0.001) and general concerns (p=0.003) than parents of low-risk infants. Beginning at 12 months, parents of high-risk atypically developing infants reported more ASD-related concerns than parents of high-risk typically developing infants (p=0.013). INTERPRETATION: Clinicians should elicit parental concerns and provide support, as parents are worried about their high-risk infants by age 6 months. Additionally, parents' abilities to identify concerns that are suggestive of ASD by age 12 months may aid in earlier screening and intervention. What this paper adds Most parents did not report concerns during early infancy. By 6 months, parents of high-risk infants reported autism spectrum disorder (ASD)-related and general concerns. By 12 months, parents of high-risk atypically developing infants identified ASD-related concerns.

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.