Background

Functional brain connectivity is altered in children and adults with autism spectrum disorder (ASD). Functional disruption during infancy could provide earlier markers of ASD, thus providing a crucial opportunity to improve developmental outcomes. Using a whole-brain multivariate approach, we asked whether electroencephalography measures of neural connectivity at 3 months of age predict autism symptoms at 18 months.

Methods

Spontaneous electroencephalography data were collected from 65 infants with and without familial risk for ASD at 3 months of age. Neural connectivity patterns were quantified using phase coherence in the alpha range (6-12 Hz). Support vector regression analysis was used to predict ASD symptoms at age 18 months, with ASD symptoms quantified by the Toddler Module of the Autism Diagnostic Observation Schedule, Second Edition.

Results

Autism Diagnostic Observation Schedule scores predicted by support vector regression algorithms trained on 3-month electroencephalography data correlated highly with Autism Diagnostic Observation Schedule scores measured at 18 months (r = .76, p = .02, root-mean-square error = 2.38). Specifically, lower frontal connectivity and higher right temporoparietal connectivity at 3 months predicted higher ASD symptoms at 18 months. The support vector regression model did not predict cognitive abilities at 18 months (r = .15, p = .36), suggesting specificity of these brain patterns to ASD.

Conclusions

Using a data-driven, unbiased analytic approach, neural connectivity across frontal and temporoparietal regions at 3 months predicted ASD symptoms at 18 months. Identifying early neural differences that precede an ASD diagnosis could promote closer monitoring of infants who show signs of neural risk and provide a crucial opportunity to mediate outcomes through early intervention.

Brain differences linked to autism spectrum disorder (ASD) can manifest before observable symptoms. Studying these early neural precursors in larger and more diverse cohorts is crucial for advancing our understanding of developmental pathways and potentially facilitating earlier identification. EEG is an ideal tool for investigating early neural differences in ASD, given its scalability and high tolerability in infant populations. In this context, we integrated EEG into an existing multi-site MRI study of infants with a higher familial likelihood of developing ASD. This paper describes the comprehensive protocol established to collect longitudinal, high-density EEG data from infants across five sites as part of the Infant Brain Imaging Study (IBIS) Network and reports interim feasibility and data quality results. We evaluated feasibility by measuring the percentage of infants from whom we successfully collected each EEG paradigm. The quality of task-free data was assessed based on the duration of EEG recordings remaining after artifact removal. Preliminary analyses revealed low data loss, with average in-session loss rates at 4.16 % and quality control loss rates at 11.66 %. Overall, the task-free data retention rate, accounting for both in-session issues and quality control, was 84.16 %, with high consistency across sites. The insights gained from this preliminary analysis highlight key sources of data attrition and provide practical considerations to guide similar research endeavors.