Visual Evoked Potentials As a Candidate Endophentype for Autism Spectrum Disorder

Background:  Sensory symptoms are common in individuals with autism spectrum disorder (ASD), particularly within the visual domain. Visual evoked potentials (VEPs) are an objective, reliable measure of early-stage visual processing that can be used to understand neural mechanisms in the brain while probing for disease pathology. The identification of endophenotypes, quantifiable, hereditary measures of risk that can help to identify links between phenotypic and genotypic variables, is critical for understanding disease susceptibility and protective factors. Previous literature has identified endophenotypes of schizophrenia using VEP paradigms. The current study seeks to examine endophenotypes of ASD using similar VEP methodology.

Objectives:  To assess the integrity of visual pathways in unaffected siblings (SIBS) of children with idiopathic ASD (iASD) compared to typically developing (TD) children and children with iASD.

Methods:  This study included children with iASD, SIBS, and TD controls between the ages of 2 and 12. ASD diagnoses were based on DSM-5 criteria, the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), and the Autism Diagnostic Interview-Revised (ADI-R). Genetic testing (chromosomal microarray) was conducted on the ASD sample to rule out the presence of a genetic finding. Children in the SIBS and TD groups were screened with the Social Responsiveness Scale, Second Edition (SRS-2). VEPs were collected using single-channel EEG recording based on the International 10-20 system with an active electrode at Oz (occipital). A battery of both transient and steady-state VEPs was collected, which included a contrast-reversing checkerboard condition to elicit transient VEPs and two isolated-check conditions using bright or dark patterns of increasing contrast to elicit steady-state VEPs.

Results:  Participants in the SIBS group displayed intermediate responses compared to the iASD and TD group for both transient and steady-state conditions. Results also replicated previous findings indicating significantly weaker VEP responses in children with iASD compared to TD controls. Specifically, significantly smaller amplitudes were found in response to the transient VEP condition and significantly smaller signal-to-noise ratios were found at low levels of contrast in the steady-state conditions, which reflects ON and OFF pathways in the brain.

Conclusions: Our results suggest that VEPs may reflect an endophenotype of ASD and are consistent with literature from neuroimaging and higher order electrophysiological studies demonstrating intermediate responses in unaffected siblings. The stimuli used in this study reflect mechanisms associated with excitatory/inhibitory imbalance (transient responses) and abnormalities in the magnocellular pathway (steady-state responses). Future studies should continue to examine these mechanisms and their potential as treatment targets. In addition, studies examining high-risk infant siblings are an important step to elucidate the relationship between VEP abnormalities and the presence of iASD.