Autism Spectrum Disorder (ASD) is a highly heritable neurodevelopmental condition associated with difficulties in social interaction / communication, the presence of stereotyped / repetitive behavior, and restricted interest or atypical response to sensor information. Although language impairment is not among the core characteristics of ASD, about 75% of children with this disorder have co-occurring language difficulties. Language functioning is highly heterogeneous in this population and can vary from severe impairment (e.g., nonverbal or minimally verbal ASD) to above-average language skills. Given the variability of language skills in this population, it is most likely that there are multiple neurobiological and genetic mechanisms that are related to language impairment in ASD.
My research program addresses biological mechanisms of language in children with ASD and other related neurodevelopmental disorders and genetic syndromes. My goal is to develop a set of biomarkers of language impairments based on neural and genetic data for early identification of language difficulties as well as predict language trajectories based on early neural markers and genetic profiles. I am addressing multilevel modeling, including genetics (single nucleotide polymorphism, genome-wide copy number variant analysis to identify genetic pathways, sequencing analysis, and gene expression analysis to reveal specific neural subtypes and clinical phenotypes), advanced electro-/magnetoencephalography (EEG/MEG) and magnetic resonance imaging (MRI) approaches, and at providing language / auditory and clinical (behavioral) assessment in children with ASD and related neurodevelopmental disorders to explore subtypes of language phenotypes and to identify their neural and genetic mechanisms.
Low-level auditory abnormalities and their relation to language impairment in children with ASD
The goal of my MEG/EEG studies is to identify how low-level auditory processing in the primary auditory cortex of children with ASD is associated with language impairments assessed behaviorally. I focused on the pure tones with different amplitude modulation (2Hz and 40Hz), simple clicks as well as pseudowords (to target phonological short-term memory) as measures that previously have been reported to be associated with language, phonological processing, and reading skills in children with developmental dyslexia. At the same time, these neural responses have not been studied widely in ASD in relation to formal language assessment. The results of the study showed a reduction of 2Hz and 40Hz Auditory Steady-State Responses, reduced M200 amplitude and sensory gating as well as unusual topology of 2Hz response in children with ASD. These auditory responses were related to language skills in ASD. Importantly, the results revealed a bilateral relation between both 2Hz ASSR and language skills and a left-hemispheric relation between 40Hz ASSR and language skills which is consistent with the recent Dual-Stream model of cortical speech processing. Potentially, these biomarkers can be used to inform speech-language intervention in autistic kids.
Anatomical brain characteristics and their association with language impairment in children with ASD
My research with structural magnetic resonance imaging (MRI), using brain morphometry and tractography techniques, has the goal to reveal specific cortical and subcortical abnormalities in children with ASD and to assess their contribution to language difficulties and core symptoms of ASD. The results revealed a metrics (cortical – grey matter thickness, gyrification; subcortical – grey matter volume) that best predicted language functioning of children with ASD but not nonverbal IQ or the severity of autistic traits. Clinical implication of these results can be of using these metrics as objective measures of language skills in ASD.
Genetic mechanisms of language impairment and variability in youth with ASD
In my first genetic study, I focused on one of the candidate genes related to language variation in ASD, namely, the contactin-associated protein-like 2 gene (CNTNAP2), a member of the Neurexin family, spanning over 2 Mb of DNA at chromosome 7q35. The results of my research showed that the polymorphism of CNTNAP2 (SNP rs2710102) was related to structural language abilities, such that participants carrying the A-allele had lower language skills in comparison to the G-allele homozygotes. However, SNP rs2710102 was not associated with more general communication abilities.