Atypical Novelty Detection ERP Responses Associated with Genetic but Not Idiopathic ASD Etiologies

Thursday, May 12, 2016: 11:30 AM-1:30 PM
Hall A (Baltimore Convention Center)
C. M. Hudac, T. DesChamps, S. J. J. Webb and R. Bernier, University of Washington, Seattle, WA
Background:   Recurrent disruptive likely gene disrupting (LGD) mutations such as CHD8 and DYRK1A have been implicated as contributing to approximately 10% of autism spectrum disorders, (ASD; Iossifov et al., 2014). To better describe the known genetic and phenotypic heterogeneity in ASD, recent work has begun to target specific neural phenotypes related to specific genotypes. One such study integrating a “genetics-first” approach with cognitive neuroscience discovered unique social phenotypes related to genetic and idiopathic etiologies of ASD (Hudac et al., 2015). However, it is still unclear how genetic disruptions impact associated aspects of ASD, such as cognitive delay.

Objectives:   We aimed to characterize the neural patterns associated with idiopathic and genetic ASD etiologies during an auditory oddball task that is known to capture both attention orientation and novelty processing mechanisms. Recruitment targeted children with ASD who had completed genetic testing in prior studies and either had a known ASD-associated truncated likely gene-disrupting mutation (LGDM; Sanders et al., 2015; Iossifov et al., 2014) or no LGDMs (Idiopathic). Prior studies have found that children with ASD exhibit attenuation of the P3 component in response to novel and infrequent stimuli (e.g., Salmond et al., 2007; Donkers et al., 2015). However, we hypothesized that children with ASD with distinct genetic etiologies may showcase differences in neurophysiological functioning.  

Methods:   Gender-matched children age 6 to 18 (M=13.5 years, SD=2.5) were enrolled in the LGD Mutation group (n=11, ASD with LGDM), Idiopathic group (n=12, ASD without LGDM), or the Typical development group (n=11, no ASD). During electroencephalography acquisition, children watched a video of a trip to the zoo while passively attending to frequent tones, infrequent tones, and novel sounds (adapted from Salmond et al., 2007). Tone stimuli (1000 or 750 Hz) were counterbalanced between subjects. Maximum amplitude at scalp electrode clusters around Cz and Fz were extracted for the P300 component (180-350 ms). We focused on difference comparisons for attention orientation (infrequent minus frequent) and novelty detection (novel minus frequent). 

Results:   Repeated measures general linear models (SPSS 19) indicated an interaction between region, condition, and group, F(2,17)=8.50, p=.024, such that the LGDM group exhibited a reduced P300 novelty detection responses (i.e., a smaller response after accounting for the response to the frequent tone) at Cz compared to TYP children, (difference = 4.26 uV, SD = 1.5, p = .031). There were no significant amplitude differences between the Idiopathic and TYP groups at Fz or Cz for either attention orienting or novelty detection comparisons (p’s>.17). 

Conclusions:   Here, children with idiopathic ASD and those with LGDMs exhibit typical patterns of attention orienting. However, children with ASD and a LGD mutation have reduced novelty detection responses, compared to typically developing children. These results indicate that the contribution of genetic etiology on functional neural mechanisms in ASD may impact specific cognitive functions more so than others.