Transient Visual Evoked Potentials in Monogenic and Idiopathic ASD
Objectives: To use tVEPs to objectively measure the integrity of multiple frequency mechanisms in children with genetically-defined ASD subtypes relative to children with idiopathic ASD and to unaffected siblings.
Methods: VEPs were obtained from children with Phelan-McDermid syndrome (PMS), Fragile X syndrome (FXS), idiopathic ASD, unaffected siblings, and typically developing (TD) controls, extracted from ongoing EEG using a single electrophysiological channel. A contrast-reversing checkerboard stimulus (100% contrast) was displayed for 60 seconds to elicit a transient VEP, which enables the examination of multiple frequency mechanisms. All participants received genetic testing to confirm diagnoses. PMS was diagnosed using chromosomal microarray or targeted sequencing, and FXS was diagnosed by analyzing the FMR1 repeat. Standardized research diagnostic instruments (ADOS-2, ADI-R) and DSM-5 criteria were used to diagnose ASD.
Results: Children with PMS displayed distinct tVEP waveforms that reflect a deficit in glutamatergic activity and lack of a high frequency response as compared to children with FXS, idiopathic ASD, unaffected siblings, and TD controls. Children in all other samples displayed the expected tVEP waveform with peaks and troughs at P0, N0, and P1. Results from a measure of magnitude squared coherence (MSC) indicated that children with PMS only showed significant responses at the lowest frequency band (6-10 Hz), while all other groups showed responses at both low and high frequencies.
Conclusions: Our results support findings from animal models which indicated glutamatergic dysregulation in PMS (Yang et al. 2012, Bozdagi et al. 2013) and the effects of SHANK3 deficiency on AMPA, NMDA, and metabotropic glutamate receptors. Fast acting ionotropic glutamate receptors are necessary to obtain a high frequency VEP response, which is absent in the data from children with PMS. This study is the first step towards identifying neural biomarkers in children with PMS. Future studies must assess electrophysiological functioning in larger samples and in other sensory modalities (e.g., auditory) to determine whether individuals with PMS have an underlying global sensory problem.