Atypicality of the N170 Event-Related Potential in Autism Spectrum Disorder: A Meta-Analysis

Background: Autism spectrum disorder (ASD) is associated with impaired processing of social information, such as faces (Lozier et al., 2014; McPartland et al., 2004). However, the neurocognitive processes that underlie social deficits in ASD are poorly understood. The N170 event-related potential (ERP) indexes early face processing in humans by electroencephalogram (EEG; Bentin et al., 1996) and has been used to index face processing impairments in psychiatric disorders (Feuerrigel et al., 2015; McCleery et al., 2015). Although the N170 is considered among the most promising biomarkers of ASD (Jeste & Nelson, 2009; McPartland et al., 2016), published literature on the N170 is not consistent, and studies often suffer from small sample sizes. No quantitative review to date has integrated the literature to assess whether N170 response to faces in individuals with ASD differs from that of typically-developing (TD) individuals.

Objectives: This meta-analysis examined the corpus of literature investigating differences in N170 response to faces in individuals with and without ASD. In addition, to examine the specificity of differential N170 response to face stimuli in particular, this study also meta-analyzed differences in a) N170 response to non-face stimuli and b) P1 response to faces in the same sample of studies.

Methods: Web of Science, PubMed, and PsycINFO databases and citation lists from past systematic reviews on the topic were searched. Data from 23 studies (N_ASD=374, N_TD=359; Table 1) were reviewed and double-coded by two independent raters (ICC>0.90). Meta-analysis was used to examine the effect size (Hedges’ g) of the difference in N170 and P1 latency and amplitude among individuals with and without ASD, averaged across all relevant facial (e.g., different emotions) and non-facial (e.g., objects, houses) stimuli for each study. Analyses were also conducted examining potential moderators (mean age and IQ of participants, sex distribution of participants, use of gold-standard ASD diagnostic measures, and ASD symptom severity) and publication bias.

Results: On average, N170 latencies to faces were delayed in individuals with ASD relative to TD participants (g=0.36, 95% CI [0.06, 0.67], p=0.02; Figure 1A), but amplitudes did not differ between ASD and TD groups overall (g=-0.03, 95% CI [-0.33, 0.26], p=0.82; Figure 1B). Moderator analyses revealed that N170 amplitudes were smaller in magnitude in the ASD relative to TD participants in adult samples (Q[1]=10.87, p=0.001) and in those with higher cognitive ability (b=0.08, p=0.006). No evidence of publication bias was found. N170 latency and amplitude to non-faces and P1 latency and amplitude to faces in the ASD group were not statistically different when compared to TD controls (all ps>0.12).

Conclusions: Atypicality of N170 response to faces, particularly increased latency, appears to be a robust biomarker of social-communicative dysfunction in ASD. This marker may relate to differential developmental experiences and use of compensatory cognitive mechanisms. Future research should further examine phenotypic differences contributing to N170 heterogeneity in ASD, as well as its malleability in response to treatment.