Frontal Theta Coherence to Gaze Fixation Is Associated with Infant Autism Risk

Background: Neural phase coherence is a fundamental mechanism underlying information processing. Abnormalities in neural coherence may reflect atypical information processing, manifesting as widespread cognitive and behavioural difficulties in a range of neuropsychiatric disorders. A growing body of evidence suggest that reduced neural phase coherence represents an endophenotype of ASD. Theta oscillations are a promising neural signature of atypical information processing given their links to attention control. Several studies suggest that ASD is characterized by reduced frontal theta coherence at rest and is correlated with attention flexibility in children. Not only have reductions in frontal theta been found in infants at risk for ASD, at risk infants also show a distinct trajectory as theta dynamics unfold across early development. A hallmark of the autism phenotype is poor attention control and atypical patterns of eye contact, particularly for mutual gaze fixation, which are thought to contribute to the broad deficits in social interaction that are common in ASD. Although much evidence points to a severe impairment in eye contact and gaze fixation in ASD, studies have not yet assessed whether inter-trial phase coherence (ITPC) of theta to gaze fixation is reduced in infants at risk for ASD.

Objectives: The goal of this study is to test whether frontal theta ITPC to gaze represents an early biomarker for ASD. To achieve this goal we will compare single trial measures of phase coherence in 6-month old infants who have an older sibling with ASD diagnosis (sib-ASD) and typically developing (TD) infants with no family history of ASD.

Methods: The target sample comes from the British Autism Study of Infant Siblings (BASIS). Infants were assessed using a dynamic gaze task. Frontal scalp regions were assessed for theta oscillatory phase coherence to gaze stimuli. Analyses were done using an open-source MATLAB toolbox, STATSLAB, which implements robust statistics for analyzing single trial EEG data in single subjects.

Results: Compared to TD controls, sib-ASD infants show reduced P400 ERP amplitude to direct gaze stimuli and lower frontal theta ITPC.

Conclusions: Reduced frontal theta ITPC to gaze fixation in at-risk infants has both theoretical and clinical implications, possibility contributing to an impairment in outcome expectation/prediction in ASD, particularly with respect to processing social cues such as eye gaze. Identifying sensitive and stable biomarkers capable of differentiating ASD risk in infancy has important clinical implications for diagnostic status, dissociation between transdiagnostic categories, and tracking treatment response.