Early Functional EEG Connectivity in Infants at Risk for Autism Associates with Later Circumscribed Interests; A Replication Study

Background:

Previous studies have suggested functional EEG connectivity as potential biomarker of Autism Spectrum Disorders (ASD). However, findings are mixed and replication is essential for application in the clinical field and understanding of underlying mechanisms. Our previous study found functional EEG hyper-connectivity in 14-month-old infants who developed ASD at a later age compared to those who did not met ASD criteria. The amount of hyper-connectivity in selected fronto-central connections was related to later severity of restricted and repetitive behaviours (RRBs) in infants who later developed ASD, whereas no associations were found with later communication difficulties.

Objectives:

The current study had three objectives: 1) replicate the findings of hyper-connectivity in infants who later develop ASD, 2) replicate the association between early hyper-connectivity and later RRBs, and 3) further investigate the latter association by looking at subtypes of RRBs.

Methods:

Functional EEG connectivity was measured with the debiased weighted phase lag index for the alpha range (7-8 Hz) from EEG recordings while 14-month-old infants watched videos. Clinical outcome and symptom severity at 36 months of age were assessed via parental interview with the Autism Diagnostic Interview – Revised (ADI-R). The final sample included infants with low familial risk (N_LR = 20), and with high familial risk who showed typical development (N_HR-TD = 47), atypical development (N_HR-Atyp = 21), or met ASD criteria (N_HR-ASD = 13) at 36 months. Global (average) connectivity values in the HR-ASD group were compared to the LR, HR-TD and HR-Atyp group separately. Spearman’s correlations were used to investigate associations between connectivity and the Repetitive Behaviour and Social and Communication scales of the ADI-R.

For correlational analyses for the subtypes of restricted and repetitive behaviours, datasets for infants with high familial risk from the previous and current study were combined. We focused on three subtypes of RRBs: repetitive motor behaviours (N_HR = 103), insistence on sameness (N_HR = 102), and circumscribed interests (N_HR = 90) measured with the ADI-R.

Results:

Global EEG connectivity in the HR-ASD group showed no significant differences compared to the LR, HR-TD, or HR-Atyp group. In the HR-ASD group, functional connectivity across selected fronto-central connections was associated with RRBs (Figure 1). No significant associations were observed with social and communication difficulties in the HR-ASD or HR group.

Further analyses in the combined datasets showed that functional EEG connectivity in the HR group was significantly associated with circumscribed interests, whereas correlations with repetitive motor behaviours and insistence on sameness did not reach significance.

Conclusions:

First, we did not replicate the finding of hyper-connectivity in the HR-ASD group compared to the other groups. The heterogeneity in ASD might underlie our failure to replicate categorical outcome findings.

Second, we did replicate the previously observed association between functional EEG connectivity and dimensional traits in HR-ASD infants. This is the first replication of an infant neural predictor of later variation in dimensional traits.

Lastly, the associations with functional connectivity were strongest for circumscribed interests. It is possible that atypical connectivity in the cortico-basal ganglia-thalamo-cortical loop underlies this observation.