Functional EEG connectivity in infants associates with later restricted and repetitive behaviours in autism; a replication study

Abstract

We conducted a replication study of our prior report that increased alpha EEG connectivity at 14-months associates with later autism spectrum disorder (ASD) diagnosis, and dimensional variation in restricted interests/repetitive behaviours. 143 infants at high and low familial risk for ASD watched dynamic videos of spinning toys and women singing nursery rhymes while high-density EEG was recorded. Alpha functional connectivity (7-8 Hz) was calculated using the debiased weighted phase lag index. The final sample with clean data included low-risk infants (N = 20), and high-risk infants who at 36 months showed either typical development (N = 47), atypical development (N = 21), or met criteria for ASD (N = 13). While we did not replicate the finding that global EEG connectivity associated with ASD diagnosis, we did replicate the association between higher functional connectivity at 14 months and greater severity of restricted and repetitive behaviours at 36 months in infants who met criteria for ASD. We further showed that this association is strongest for the circumscribed interests subdomain. We propose that structural and/or functional abnormalities in frontal-striatal circuits underlie the observed association. This is the first replicated infant neural predictor of dimensional variation in later ASD symptoms.

Fig. 1. Overview of the methods used.

Methods are the same as in the previous study. EEG was recorded while 14-month-old infants watched dynamic videos. At 36 months, a clinical assessment and measurements of dimensional ASD traits were performed. Developmental abilities were assessed at both visits. EEG data were cleaned, preprocessed, and cut into 1-s epochs. After Fast Fourier Transformations, the debiased Weighted Phase Lag Index (dbWPLI) was calculated. Connectivity matrices contain connectivity values for each possible connection pair. These were averaged across the frequencies for the 7–8 Hz band. We used the connectivity matrices of each infant to assess network differences between groups with the Network Based Statistics program. Global dbWPLI was calculated by averaging values below the diagonal of the connectivity matrices. These values were used to assess differences on group level. Finally, average connectivity in selected connections only (here displayed in yellow) was used to investigate the correlations between functional connectivity and dimensional traits. MSEL Mullen Scales for Early Learning, ADI-R Autism Diagnostic Interview–Revised, ADOS-2 Autism Diagnostic Observational Schedule–2, NBS Network Based Statistics, dbWPLI debiased Weighted Phase Lag Index

Fig. 2. Functional EEG connectivity and categorical outcome.

a Mean (standard error of the mean, in blue) and median (red) global dbWPLI (averaged across all electrodes) for each group for 0 to 30 Hz. The alpha band (7–8 Hz) is highlighted in cyan. b Topoplots for global dbWPLI across the alpha band (average connectivity for one electrode with all other 115 electrodes) for each group. c Global dbWPLI for the alpha band (7–8 Hz) for each group. Each square represents an individual participant. Red horizontal lines display group medians. N_LR = 20, N_HR-TD = 47, N_HR-Atyp = 21, and N_HR-ASD = 13

Fig. 3. Correlations between global connectivity and dimensional traits.

a Global connectivity among selected connections and scores on the ADI-R RRB total at 36 months of age for HR-ASD infants only. b Global connectivity across all connections and scores on the ADI-R RRB total at 36 months of age for the complete HR sample. c Global connectivity across all connections and scores on the ADI-R Social and Communication Scale Total at 36 months of age for the complete HR sample. Each asterisk represents one infant: black for HR-TD infants, cyan for HR-Atyp infants, and purple for HR-ASD infants. R and p values in the left upper corners reflect values for the lines in the scatterplots