EEG functional connectivity in infants at elevated familial risk for autism spectrum disorder

Abstract

Background: Many studies have reported that autism spectrum disorder (ASD) is associated with atypical structural and functional connectivity. However, relatively little is known about the development of these differences in infancy and on how trajectories may vary between sexes.

Methods: We used the International Infant EEG Platform (EEG-IP), a high-density electroencephalogram (EEG) dataset pooled from two independent infant sibling cohorts, to characterize such neurodevelopmental deviations during the first years of life. EEG was recorded at 6, 12, and 18 months of age at typical (N=97) or high familial risk for ASD (N=98), determined by the presence of an older sibling with a confirmed ASD diagnosis. We computed the functional connectivity between cortical EEG sources during video watching using the corrected imaginary part of phase-locking values.

Results: Our findings showed low regional specificity for group differences in functional connectivity but revealed different sex-specific trajectories between females and males in the group of high-risk infants. Specifically, functional connectivity was negatively correlated with ADOS calibrated severity scores, particularly at 12 months for the social affect score for females and for the restrictive and repetitive behaviors for males.

Limitations: This study has been limited mostly due to issues related to the relatively small effective sample size inherent in sibling studies, particularly for diagnostic group comparisons.

Conclusions: These results are consistent with sex differences in ASD observed in previous research and provide further insights into the role of functional connectivity in these differences.

Keywords: ADOS; Autism spectrum disorder; electroencephalography; functional connectivity; infants; longitudinal; sex differences; sibling studies; source reconstruction.

Figure 1.. Average logit-transformed CIPLV connectivity.

Displayed as a function of the age (x-axis), the site (columns), biological sex (row), and the diagnostic outcome groups (color). Whiskers represent the bootstrapped 95% confidence intervals. These plots are for all-to-all connectivity averaged by recording.

Figure 2.. Functional connectivity (CIPLV) plots.

Displayed for the three diagnostic groups (upper three graphs) and corresponding plots for the difference between the TLA and the two subgroups of ELA infants (lower two panels). The three top graphs and the two bottom graphs have been plotted using the same colormaps to allow fair comparisons. The left (right) side of these plots corresponds to the left (right) hemisphere. The order of the regions in each hemisphere is the same and is shown on the left side of the figure, from posterior (bottom) to anterior (top) regions. These plots only show the 100 region pairs with the strongest connectivity (top three panels) and the 100 pairs with the strongest between-group differences in connectivity (bottom two panels).

Figure 3.. Logit-transformed CIPLV values within the different resting-state networks.

Displayed per network (different panels), time points (x-axis), and diagnostic groups (color). Whiskers represent the bootstrapped 95% confidence interval.

Figure 4.. Average logit-transformed CIPLV connectivity as a function of the distance.

Displayed between regions (x-axis), age (rows), site (columns), and group (color). To smooth these lines, distances are split into 20 bins each covering 5% of the distribution. Shaded regions show 95% bootstrapped confidence intervals.

Figure 5.. Regression between the logit-transformed CIPLV connectivity and ADOS calibrated severity scores for the ELA infants.

Displayed per sex (rows), time point (columns), and sites (blue: London; red: Seattle; black: Pooled). The dashed lines indicate the average connectivity for TLA infants. Pearson’s coefficients of correlation (rho) are indicated, along with p-values (p) from robust linear regressions. Stars indicate participants diagnosed with ASD, whereas dots indicate neurotypical individuals. a) Social affect. b) RRBs. Overall ADOS severity scores are shown in supplementary figure 3.