Cortical Auditory Processing of Simple Stimuli Is Altered in Autism: A Meta-analysis of Auditory Evoked Responses

Abstract

Background: Auditory perceptual abnormalities are common in persons on the autism spectrum. The neurophysiologic underpinnings of these differences have frequently been studied using auditory event-related potentials (ERPs) and event-related magnetic fields (ERFs). However, no study to date has quantitatively synthesized this literature to determine whether early auditory ERP/ERF latencies or amplitudes in autistic persons differ from those of typically developing control subjects.

Methods: We searched PubMed and ProQuest for studies comparing 1) latencies/amplitudes of P1/M50, N1b, N1c, M100, P2/M200, and/or N2 ERP/ERF components evoked by pure tones and 2) paired-click sensory gating (P1/N1b amplitude suppression) in autistic individuals and typically developing control subjects. Effects were synthesized using Bayesian 3-level meta-analysis.

Results: In response to pure tones, autistic individuals exhibited prolonged P1/M50 latencies (g = 0.341 [95% credible interval = 0.166, 0.546]), prolonged M100 latencies (g = 0.319 [0.093, 0.550]), reduced N1c amplitudes (g = -0.812 [-1.278, -0.187]), and reduced N2 amplitudes (g = -0.374 [-0.633, -0.179]). There were no practically significant group differences in P2/M200 latencies, N2 latencies, P1/M50 amplitudes, N1b amplitudes, M100 amplitudes, or P2/M200 amplitudes. Paired-click sensory gating was also reduced in autistic individuals (g = -0.389 [-0.619, -0.112]), although this effect was primarily driven by smaller responses to the first click stimulus.

Conclusions: Relative to typically developing control subjects, autistic individuals demonstrate multiple alterations in early cortical auditory processing of simple stimuli. However, most group differences were modest in size and based on small numbers of heterogeneous studies with variable quality. Future work is necessary to understand whether these neurophysiologic measures can predict clinically meaningful outcomes or serve as stratification biomarkers for the autistic population.

Keywords: Auditory; Autism spectrum disorder; Electroencephalography (EEG); Event-related potential; Magnetoencephalography (MEG); Meta-analysis.

Figure 1.

Posterior density forest plots of: (A) P1/M50 latency effects, (B) M100 latency effects, (C) P1/M50 amplitude effects, and (D) M100 amplitude effects. The standardized mean difference (SMD) and 95% credible interval (CrI) for each study represent the posterior distribution of that study’s mean effect size, conditional on prior beliefs and the observed data. Negative values of g indicate smaller values of a variable in the autism group (i.e., less negative amplitude, faster component latencies), compared to TD controls. The gray shaded areas indicate the region of practical equivalence (ROPE) for each comparison. Raw effect sizes from each study and forest plots for the remaining outcomes can be found in Supplemental Materials.

Figure 2.

(A) Posterior density forest plots of P1/N1b amplitude suppression effects. The standardized mean difference (SMD) and 95% credible interval (CrI) for each study represent the posterior distribution of that study’s mean effect size, conditional on prior beliefs and the observed data. Negative values of g indicate reduced sensory gating ability (i.e., less effective amplitude suppression) in the autism group compared to TD controls. The gray shaded area indicates the region of practical equivalence (ROPE). Raw effect sizes from each study can be found in Supplemental Table S10. (B) Summary posterior densities of P1 amplitude differences to the first and second clicks of the paired-click paradigm, as compared to the posterior distribution of P1 amplitude suppression effects. Autistic individuals demonstrate smaller P1 amplitudes in response to the initial click, driving a group difference in amplitude suppression metrics.