Early-Stage Visual Processing Abnormalities in Children with ASD and Unaffected Siblings

Background: Previous studies have described atypical perceptual processing in children with ASD, as well as a high prevalence of sensory symptomotology. However, the early stages of sensory processing, specifically within the visual cortex, remain underexplored. Quantitative and objective measures can be obtained through noninvasive electrophysiological testing based on extracting the visual evoked potential (VEP) from the ongoing electroencephalogram (EEG). These measures may elucidate underlying neural correlates of ASD and they offer the capability to track neural development and monitor the effects of treatment.

Objectives: (1) To develop and implement a battery of short-duration neurophysiological tests that can be used to assess the integrity of visual pathways in children with ASD, and (2) to examine differences in the visual pathways of children with ASD, unaffected siblings and typically developing controls. 

Methods: Transient and steady-state VEP recordings were obtained from 11 children with ASD (M_age = 9.09, SD = 2.34), 12 control participants (M_age = 7.17, SD = 2.56), and 5 unaffected siblings (M_age = 6.00; SD = 1.58) using the Neucodia system (VeriSci Corp.). In short-duration runs, each stimulus condition was presented for ~ 2 s and the EEG was recorded synchronized to the display’s frame rate. Stimulus conditions (10-deg field, mean/background luminance = 50 cd/m²) included a contrast-reversing checkerboard (100% contrast) to elicit transient VEPs (tVEP), used to examine multiple frequency mechanisms, a pair of radial patterns (partial-windmill and windmill-dartboard) with elements contrast-reversed at ~ 4 Hz (32% contrast) to elicit steady-state VEPs (ssVEP), used to quantify direct-through excitatory and lateral inhibitory contributions to the response, and a dartboard with each element contrast-reversed by a sum of high frequency sinusoids (22.8 & 24.8 Hz, 32% contrast/sinusoid) to yield an intermodulation response at 2 Hz that reflects excitatory nonlinear interactions. In addition, contrast-sweep conditions (bright or dark isolated checks) in which contrast increased in octave steps from 2-64% elicited ssVEPs at 12.5 Hz to assess ON/OFF pathways, respectively. ASD diagnoses were determined based on research diagnostic instruments (ADOS, ADI-R) and DSM-IV-TR criteria. 

Results: Differential effects were observed across stimulus conditions. Children with ASD and unaffected siblings both displayed deficits in low contrast responses, particularly under conditions that emphasize contributions from the magnocellular pathway. Increased neural noise was also observed in both the ASD and unaffected sibling groups. In contrast, the ASD group displayed evidence of strong GABA-ergic inhibition and enhanced short-range lateral interactions. No differences were observed in the excitatory contributions to the VEP in response to the two-sinusoid condition.  

Conclusions: The use of low-level, non-social, stimuli provide evidence for both enhanced and weakened visual processing in the early visual pathways of children with ASD and unaffected siblings. Further studies are needed to examine whether these differences persist in larger samples and in more specific age cohorts. Short-duration VEPs hold promise as a rapid and reliable method to examine electrophysiological biomarkers, or endophenotypes, of ASD. Findings also demonstrate that short-duration stimuli, in conjunction with multivariate statistical analysis of the brain’s responses, can yield sensitive and objective indices of particular neural pathways.