Comparison of Neural Response to Language in Infants at Elevated Risk for ASD and in Infants with Nonsyndromic Craniosynostosis

Background: Autism spectrum disorder (ASD) is characterized by impaired social interaction and communication. While language skills vary widely among individuals with ASD, language delay in infants is an important prognostic feature of ASD severity. The study of auditory event-related potentials (ERPs) in infants at high-risk for ASD (HR-ASD) has demonstrated atypical responses in several ERP components compared to typically-developing (TD) controls. To better understand the specificity of atypical neural response to language in ASD, clinical comparisons are needed. Nonsyndromic craniosynostosis (NSC), a congenital disorder characterized by the premature fusion of cranial vault sutures, is associated with impairments in learning and language that may resemble the deficits found in ASD. Mismatch negativity (MMN), an ERP component found between 80-300ms, has been used to index language acquisition via the phenomenon of perceptual narrowing.

Objectives: To compare neural response to auditory stimuli in HR-ASD and NSC in order to characterize specificity of language acquisition deficits in ASD.

Methods: 12 HR-ASD infants were recruited from the Yale Autism Program. 15 infants with NSC were enrolled from the Yale Craniofacial Clinic. 35 TD infants were used as age-matched controls. Participants were presented with a non-native phoneme discrimination task involving five blocks of ten repetitions each of the Hindi retroflex phoneme /da/ and the dental phoneme /da/ in random order. Auditory stimuli were presented at 80 dB, and EEG was recorded at 250 Hz using a 128-channel HydroCel Geodesic Sensor Net. Analysis focused on selected electrode clusters from four regions of interest: the left frontal, right frontal, left central, and right central clusters. The MMN component was calculated as the largest negative amplitude in the difference wave between 80-300ms after the stimulus.

Results: In the left frontal region, HR-ASD demonstrated marginally attenuated MMN compared to TDs (p=.092), while NSC demonstrated significantly attenuated MMN compared to TDs (p=.011). There were no significant differences in any electrode cluster between HR-ASD and NSC (ps>.05). All other pairwise comparisons did not show significant differences in MMN amplitude between different groups or within groups in different brain regions.

Conclusions: Previous work has shown that while TD infants demonstrate lateralized response to language, neither HR-ASD nor NSC infants display significant hemispheric lateralization. This atypical lateralization has previously been suggested to be an endophenotype of ASD that can be detected early in life. Our current study revealed significantly decreased MMN amplitude in NSC but not HR-ASD infants. Thus, while HR-ASD and craniosynostosis may share certain similarities in auditory response, such as atypical lateralization, there may also be differing neural processes that distinguish these two. Results suggest that additional research is required to understand variably impacted MMN in HR-ASD populations.