EEG Connectivity in Infants at High Risk for Autism

Background:   It has been previously reported that structural and functional brain connectivity in individuals with autism spectrum disorders (ASD) is atypical and that the extent and directions of the abnormality may vary with age. However, to date, no measures of functional connectivity measured within the first 2 years have specifically associated with a later ASD diagnosis.

Objectives:   In the present study we analysed functional brain connectivity in 14-month-old infants at high and low familial risk for ASD using electroencephalography (EEG). We aimed to investigate if abnormal EEG connectivity during infancy predicts later ASD outcome.

Methods: EEG was recorded while infants attended to videos. We focused on the infant alpha band, because it is 1) intimately related to attention processes; 2) less prone to variations in infant’s cognitive and emotional engagement than the theta rhythm; and 3) less likely to be contaminated by cranial muscle artefacts then the EEG oscillations of higher frequencies. Alpha connectivity was assessed using debiased weighted phase lag index (dbWPLI) – a recently developed method that is robust to volume conduction effect.  Infant’s behaviour during EEG session (looking, motion, affect, etc) was recorded and coded off-line. At 36 months the high-risk infants were assessed for symptoms of ASD.

Results:   In all experimental groups the functional connectivity peaked in the alpha frequency range (7-8 Hz). As a group, high-risk infants who were later diagnosed with ASD demonstrated elevated phase-lagged alpha-range connectivity as compared to both low-risk infants, and to high-risk infants who did not go on to ASD.  Hyper-connectivity was most prominent over frontal and central areas. The degree of hyper-connectivity at 14 months correlated with the severity of restricted and repetitive behaviours in participants with ASD at 3 years.  As the group differences in functional connectivity may reflect differences in behaviour during the EEG session, we conducted detailed analysis of infant’s behaviour during EEG recording.  No group differences were observed in attentiveness to the movies, amount of gross body movements, or amount of time when participants demonstrated negative/positive affect. Further, no group differences in absolute or relative alpha spectral power were found.

Conclusions: At least some infants later diagnosed with ASD demonstrate functional hyper-connectivity in the alpha frequency range.  This hyper-connectivity cannot be accounted for by inter-individual differences in behaviour during EEG session or by inter-individual differences in EEG spectral power, but seems to constitute an important feature of the early neurophysiological phenotype.