Atypical Neural Sensory Processing of Auditory Stimulus Change Among Children with De Novo Disruptive Mutations to SCN2A
Objectives: Characterization of the phenotype associated with disruptive SCN2A mutations is critical to understanding genotype-phenotype relations and illuminating the pathophysiology of ASD in genetically defined subgroups. This study aims to contribute to a fuller description of the SCN2A phenotype by examining neural correlates of sensory processing.
Methods: Children with de novo mutations to SCN2A and their biological siblings participated in an auditory oddball event-related potential task measuring low-level sensory processing of auditory stimulus change. To date, participants included children with de novo SCN2A mutations (n = 8, 5 male, 5 ASD, mean age = 10.77, range = 5.75 - 15.58) and their biological parents (n = 17, mean age = 43.35, range = 35.0 – 51.25), siblings (n = 5, 3 male, mean age = 9.18, range = 4.58 - 17.58). ERP Paradigm:Standard pure tones (82%), and deviant tones varying in duration (6%), frequency (6%), and combined duration and frequency (6%) were presented during passive viewing of a silent movie. Responses to deviant tone types were averaged together. Peak latency of the P3a component were extracted from frontocentral medial electrodes.
Results: Preliminary analyses were conducted in SAS 9.4 using multilevel models tested condition and group differences. A random-intercept single-trial analysis was utilized to account for ongoing variance across the session. All groups exhibited a faster P3a latency to deviant compared to standard conditions, F(2, 32000) = 149.65, p < .0001. A group by condition interaction on P3a peak latency, F(2, 32000) = 21.39, p < .0001, indicated that SCN2A carriers had less condition discrimination (diff = 3.56 ms, p = .0033) than parents (diff = 11.12 ms, p < .0001) or siblings (diff = 6.01 ms, p < .0001).
Compared to non-carrier relatives, SCN2A carriers exhibited reduced neural discrimination between standard and deviant tones as measured by P3a latency. This finding suggests diminished sensory sensitivity to auditory stimulus change among SCN2A carriers and a potential reduction in bottom-up regulatory systems that are critical for attending to and integrating information in the environment. Future efforts to characterize the SCN2A phenotype will examine relationships between atypical sensory processing and behavioral features.