Date of Completion

7-28-2014

Embargo Period

7-27-2017

Keywords

developmental language disorder, specific language impairment, neurophysiology, genetics, genome-wide association study, event-related potentials, memory, language

Major Advisor

Dr. James S. Magnuson

Associate Advisor

Dr. Nicole Landi

Associate Advisor

Dr. Kenneth Pugh

Field of Study

Psychology

Degree

Doctor of Philosophy

Open Access

Campus Access

Abstract

Four electrophysiological studies (using event-related potentials, ERPs) and one genome-wide association (GWAS) study investigated the neurophysiological and genetic bases of Developmental Language Disorder (DLD) in a geographically isolated Russian-speaking population with an elevated prevalence of DLD. Experiments 1 and 2 found that while children with DLD showed intact preattentive phonological discrimination mismatch negativity (MMN) component, they showed reduced amplitudes of the auditory P2 and P3b components in an attentional oddball task. These amplitudes were related to measures of lexical development and development of complex syntax, underscoring the role of working memory and attentional limitations in DLD. Experiment 3 examined lexical processing (i.e., the N400 component) in children with DLD and their typically developing (TD) peers and established the presence of lexical processing deficits in DLD potentially mediated by their phonological deficits but largely unrelated to deficits in grammatical development. Experiment 4 investigated children’s neural responses to violations of subject-verb grammatical gender agreement in Russian. Children with DLD showed a left-lateralized P600 in response to the morphologically-taxing violations, absent in TD children; they also showed a reduced amplitude of the P200-like component in response to verbs in general, suggesting the presence of early phonological and/or morphological processing deficits. The molecular genetic GWAS study identified a novel candidate DLD gene, SETBP1, located on chromosome 18q21 and associated with measures of the development of complex syntax. The patterns of intercorrelations between behavioral measures of cognitive/language development and ERPs and intercorrelations among ERPs suggested that behavioral heterogeneity of DLD manifestations is accompanied by its neurocognitive heterogeneity. Coupled with the results from the GWAS study, these findings support viewing DLD as a complex common neurodevelopmental disorder that is multivariate, dimensional and etiologically heterogeneous even when overall heterogeneity is reduced at both environmental and genetic levels.

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